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Sample records for frontotemporal dementia patients

  1. Treatment of Frontotemporal Dementia

    OpenAIRE

    Tsai, Richard M.; Boxer, Adam L.

    2014-01-01

    Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative diseases with heterogeneous clinical presentations and two predominant types of underlying neuropathology. FTD typically comprises three distinct clinical syndromes: behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), and nonfluent variant primary progressive aphasia (nfvPPA). FTD also frequently overlaps both clinically and neuropathologically with three other neuro...

  2. Self-Consciousness in Patients with Behavioral Variant Frontotemporal Dementia.

    Science.gov (United States)

    Arroyo-Anlló, Eva M; Bouston, Adèle Turpin; Fargeau, Marie-Noëlle; Orgaz Baz, Begõna; Gil, Roger

    2016-01-01

    Self-consciousness (SC) is multifaceted and considered to be the consciousness of one's own mental states. The medial prefrontal cortex may play a critical role in SC. The main aim of this paper was to examine SC in patients with behavioral variant frontotemporal dementia, who are characterized more by changes in personal, social, and emotional conduct and loss of insight than by cognitive disturbances. Control and patient groups of 21 subjects each, matched by age, educational level, gender, and nationality were assessed using a SC questionnaire. It measures several aspects: Personal identity, Anosognosia, Affective state, Body representation, Prospective memory, Introspection, and Moral judgments. The most disturbed ones in patients were Anosognosia, Affective state, and Moral judgments, and the least disturbed aspects were awareness of identity and of body representation. No significant correlations were found between the SC score and any clinical or demographical characteristics. The core deficiency of SC in patients was related to behavioral SC aspects, which are more dependent on orbito-frontal functioning.

  3. [Genetic tau-variants in patients with frontotemporal dementia].

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    Ibach, Bernd; Wittmann, Markus; Pfannenschmid, Frank; Poljansky, Stefan; Haen, Ekkehard; Hajak, Göran

    2004-11-01

    [corrected] To evaluate tau-associated genetic polymorphisms in patients with sporadic frontotemporal dementia (FTD) and healthy control subjects. Tau-gene sequence of 30 patients with FTD and 30 healthy controls was analysed by polymerase-chain-reaction (PCR). Subsequent sequencing was performed to identify exonic and intronic differences between both groups. The following polypmorphisms, which are localized closely to each exon-intron-border, have been identified: In 37 % (n = 11) of the control subjects three different intronic polymorphisms occur simultaneously (Intron 2, 263, C --> Y; Intron 3, 590, A --> R; Intron 11, 150, G --> A). In the FTD group, this coexistance has been observed only in 17 % (n = 5). In how far there exists a significant correlation between the newly identified triple polymorphism in the Tau gene and an alternated risk for FTD must be evaluated in a lager population. The proximity of these polymorphisms to the exon-intron border would facilitate functional influences on gene expression patterns. These preliminary results described, above potentially point to further pathogenetic factors in the genesis of FTD.

  4. Reversal of pathology in CHMP2B-mediated frontotemporal dementia patient cells using RNA interference

    DEFF Research Database (Denmark)

    Nielsen, Troels Tolstrup; Mizielinska, Sarah; Hasholt, Lis;

    2012-01-01

    BACKGROUND: Frontotemporal dementia is the second most common form of young-onset dementia after Alzheimer's disease, and several genetic forms of frontotemporal dementia are known. A rare genetic variant is caused by a point mutation in the CHMP2B gene. CHMP2B is a component of the ESCRT...... role in the pathogenesis of the disease. METHODS: In the present study, we used lentiviral vectors to efficiently knockdown CHMP2B by delivering microRNA embedded small hairpin RNAs. RESULTS: We show that CHMP2B can be efficiently knocked down in patient fibroblasts using an RNA interference approach...

  5. Frontotemporal Dementias: A Review

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    Wilkins Kirsten

    2007-06-01

    Full Text Available Abstract Dementia is a clinical state characterized by loss of function in multiple cognitive domains. It is a costly disease in terms of both personal suffering and economic loss. Frontotemporal dementia (FTD is the term now preferred over Picks disease to describe the spectrum of non-Alzheimers dementias characterized by focal atrophy of the frontal and anterior temporal regions of the brain. The prevalence of FTD is considerable, though specific figures vary among different studies. It occurs usually in an age range of 35–75 and it is more common in individuals with a positive family history of dementia. The risk factors associated with this disorder include head injury and family history of FTD. Although there is some controversy regarding the further syndromatic subdivision of the different types of FTD, the three major clinical presentations of FTD include: 1 a frontal or behavioral variant (FvFTD, 2 a temporal, aphasic variant, also called Semantic dementia (SD, and 3 a progressive aphasia (PA. These different variants differ in their clinical presentation, cognitive deficits, and affected brain regions. Patients with FTD should have a neuropsychiatric assessment, neuropsychological testing and neuroimaging studies to confirm and clarify the diagnosis. Treatment for this entity consists of behavioral and pharmacological approaches. Medications such as serotonin reuptake inhibitors, antipsychotics, mood stabilizer and other novel treatments have been used in FTD with different rates of success. Further research should be directed at understanding and developing new diagnostic and therapeutic modalities to improve the patients' prognosis and quality of life.

  6. Frontotemporal dementia in The Netherlands : patient characteristics and prevalence estimates from a population-based study

    NARCIS (Netherlands)

    Rosso, Sonia M; Donker Kaat, Laura; Baks, Timo; Joosse, Marijke; de Koning, Inge; Pijnenburg, Yolande; de Jong, Daniëlle; Dooijes, Dennis; Kamphorst, Wouter; Ravid, Rivka; Niermeijer, Martinus F; Verheij, Frans; Kremer, H P; Scheltens, Philip; van Duijn, Cornelia M; Heutink, Peter; van Swieten, John C

    Since 1994, a population-based study of frontotemporal dementia (FTD) in The Netherlands has aimed to ascertain all patients with FTD, and first prevalence estimates based on 74 patients were reported in 1998. Here, we present new prevalence estimates after expansion of our FTD population to 245

  7. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study.

    NARCIS (Netherlands)

    S.M. Rosso (Sonia); L. Donker Kaat (Laura); T. Baks (Timo); M. Joosse (Marijke); I. de Koning (Inge); Y. Pijnenburg (Yolande); D. de Jong (Danielle); D. Dooijes (Dennis); W. Kamphorst (Wouter); R. Ravid (Rivka); M.F. Niermeijer (Martinus); F. Verheij (Fop); H.P. Kremer; P. Scheltens (Philip); C.M. van Duijn (Cock); P. Heutink (Peter); J.C. van Swieten (John)

    2003-01-01

    textabstractSince 1994, a population-based study of frontotemporal dementia (FTD) in The Netherlands has aimed to ascertain all patients with FTD, and first prevalence estimates based on 74 patients were reported in 1998. Here, we present new prevalence estimates after expansion of our FTD populatio

  8. Semantic and gender priming in frontotemporal dementia.

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    Repetto, Claudia; Manenti, Rosa; Cappa, Stefano; Miniussi, Carlo; Riva, Giuseppe

    2009-01-01

    Modifications of language processing can be observed both in normal aging and in the most common forms of degenerative dementia, such as Alzheimer's disease and the spectrum of frontotemporal dementias. The present experiment tests at the same time semantic and syntactic aspects of language processing in patients with frontotemporal dementia, using an online paradigm that allows researchers to evaluate the real linguistic competence of the patients.

  9. Somatic complaints in frontotemporal dementia

    OpenAIRE

    Landqvist, Maria; Santillo, Alexander; Gustafson, Lars; Englund, Elisabet; Passant, Ulla

    2014-01-01

    Frontotemporal dementia (FTD) is associated with a broad spectrum of clinical characteristics. The objective of this study was to analyze the prevalence of unexplained somatic complaints in neuropathologically verified FTD. We also examined whether the somatic presentations correlated with protein pathology or regional brain pathology and if the patients with these somatic features showed more depressive traits. Ninety-seven consecutively neuropathologically verified FTLD patients were select...

  10. Frontotemporal Dementia: clinical, genetic, and pathological heterogeneity

    NARCIS (Netherlands)

    H. Seelaar (Harro)

    2011-01-01

    textabstractThe current clinical syndrome frontotemporal dementia (FTD) was first described in 1892 by the Czech psychiatrist Arnold Pick. He described a patient with aphasia and behavioural changes with on macroscopic examination marked left frontotemporal atrophy. In 1911, Alois Alzheimer describe

  11. Frontotemporal Dementia: clinical, genetic, and pathological heterogeneity

    NARCIS (Netherlands)

    H. Seelaar (Harro)

    2011-01-01

    textabstractThe current clinical syndrome frontotemporal dementia (FTD) was first described in 1892 by the Czech psychiatrist Arnold Pick. He described a patient with aphasia and behavioural changes with on macroscopic examination marked left frontotemporal atrophy. In 1911, Alois Alzheimer

  12. [Neuropathology of frontotemporal dementia].

    Science.gov (United States)

    Murayama, Shigeo

    2008-11-01

    Frontotemporal dementia (FTD) is a clinical phenotype of dementia, characterized by complex of clinical symptoms, including disinhibition, character change, increased appetite, sexual misconduct and language problems. Frontotemporal lobar degeneration (FTLD) is a pathological classification of neurodegenerative disorder and its core consists of Pick's disease (PiD). Historically, PiD was morphologically subclassified into three types, but recent immunocytochemical investigations defined type I as PiD with Pick bodies (three repeat tauopathy), type II as corticobasal degeneration (CBD, four repeat tauopathy) and type III as FTLD with ubiquitinated inclusions (FTLD-U). The recent progress provided an evidence that the majority of FTLD-U represented primary TDP 43 proteionopathy. Three major clinical phenotypes of FTLD consist of FTD, semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Clinical and pathological correlative studies demonstrated that majority of the background pathology of FTD is PiD with Pick bodies, that of SD is FTLD-U and that of PNFA is CBD, although there are too many exceptions. Although FTD is one of the major clinical manifestations of FTLD, the most frequent pathological background of FTD is Alzheimer disease (AD). The degenerative processes causing FTD symptoms include dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and argyrophilic grain disease. Moreover, vascular process such as Binswanger disease and inflammatory process such as neurosyphilis could also present with FTD symptoms. Since FTD requires special clinical care distinct from AD, clinical diagnosis of FTD is quite important. But for the fundamental treatment based on background pathological processes, surrogate biomarkers, including structural and functional neuroimages and findings of cerebrospinal fluid, blood and urine, should be pursued for future progress in FTD research.

  13. Neuropsychiatric Symptoms in a Cohort of Patients with Frontotemporal Dementia: Our Experience

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    Chandra, Sadanandavalli Retnaswami; Issac, Thomas Gregor; Korada, Suresh Kumar; Teja, Karru Venkata Ravi; Philip, Mariamma

    2016-01-01

    Introduction: About 20–50% of relatively young onset dementia belongs to frontotemporal type. Most of these patients are diagnosed as psychiatric illness as their memory and instrumental activities of daily living remain unaltered till late and most of these patients do not qualify for dementia by the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. In this study, we analyzed the behavioral symptoms in our patients with radiologically and neuropsychologically proven as probable behavioral variant of frontotemporal dementia (FTD). Patients and Methods: Twenty patients qualifying the International Consensus Criteria were included and evaluated using National Institute of Mental Health and Neurosciences neuropsychological battery in addition to all mandatory dementia workup. Results: The mean age was 53.9 ± 9.9 years and the mean duration of illness was 2 ± 1.3 years. Sixty percent of them were Memory impairment was found in only 11.1% as against 25% in western studies. Disinhibition, eating problems, stereotyped behavior, delusions, and paranoia were comparable between the study population and literature. Discussion and Conclusion: There are minor variations in the neuropsychological manifestations in our patients compared to western population. Agitation and aggression are more and memory impairment is very less making the diagnosis of FTD possible only if there is a high degree of suspicion. These symptoms are less amenable for pharmacotherapy and therefore, there is a need to explore the benefits of nonpharmacological treatment options such as yoga and meditation. PMID:27570344

  14. Behavioral variant frontotemporal dementia with dominant gait disturbances - case report.

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    Wojciech Guenter

    2016-04-01

    Presented case emphasises the significance of accurately gathered anamnesis with patient and his family. Behavioural variant frontotemporal dementia should be considered in cases of unexplained gait abnormalities.

  15. Postmorbid learning of saxophone playing in a patient with frontotemporal dementia.

    Science.gov (United States)

    Cho, Hanna; Chin, Juhee; Suh, Mee Kyung; Kim, Hee Jin; Kim, Yeo Jin; Ye, Byoung Seok; Lee, Na Kyung; Kim, Eun Joo; Seo, Sang Won; Na, Duk L

    2015-01-01

    Some patients with frontotemporal dementia (FTD) show an artistic enhancement of musical abilities. However, no patients with FTD, to date, have been reported to be able to learn how to play a musical instrument after disease onset. Herein we describe a patient (J. K.) who had never played any musical instruments premorbidly, but who learned to play the saxophone after being diagnosed with a behavioral variant of FTD. He mastered a repertoire that consisted of 10 pieces of Korean folk songs over a period of three years. Furthermore, his saxophone skills were high enough to outperform other students in his class.

  16. Frontotemporal Dementia: clinical, genetic, and pathological heterogeneity

    OpenAIRE

    Seelaar, Harro

    2011-01-01

    textabstractThe current clinical syndrome frontotemporal dementia (FTD) was first described in 1892 by the Czech psychiatrist Arnold Pick. He described a patient with aphasia and behavioural changes with on macroscopic examination marked left frontotemporal atrophy. In 1911, Alois Alzheimer described the detailed microscopic changes, including argyrophilic neuronal inclusions, which are still known as Pick bodies. The term Pick’s disease was introduced in 1926 and was used till the early 90’s...

  17. Neuropsychiatric symptoms in a cohort of patients with frontotemporal dementia: Our experience

    Directory of Open Access Journals (Sweden)

    Sadanandavalli Retnaswami Chandra

    2016-01-01

    Full Text Available Introduction: About 20–50% of relatively young onset dementia belongs to frontotemporal type. Most of these patients are diagnosed as psychiatric illness as their memory and instrumental activities of daily living remain unaltered till late and most of these patients do not qualify for dementia by the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. In this study, we analyzed the behavioral symptoms in our patients with radiologically and neuropsychologically proven as probable behavioral variant of frontotemporal dementia (FTD. Patients and Methods: Twenty patients qualifying the International Consensus Criteria were included and evaluated using National Institute of Mental Health and Neurosciences neuropsychological battery in addition to all mandatory dementia workup. Results: The mean age was 53.9 ± 9.9 years and the mean duration of illness was 2 ± 1.3 years. Sixty percent of them were <60 years. There were 9 males and 11 females. Most common heralding symptom noticed in 85% of the patients was irritability and aggression as against apathy in 100% in western studies. Memory impairment was found in only 11.1% as against 25% in western studies. Disinhibition, eating problems, stereotyped behavior, delusions, and paranoia were comparable between the study population and literature. Discussion and Conclusion: There are minor variations in the neuropsychological manifestations in our patients compared to western population. Agitation and aggression are more and memory impairment is very less making the diagnosis of FTD possible only if there is a high degree of suspicion. These symptoms are less amenable for pharmacotherapy and therefore, there is a need to explore the benefits of nonpharmacological treatment options such as yoga and meditation.

  18. Detection of residual cognitive function through nonspontaneous eye movement in a patient with advanced frontotemporal dementia

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    Akira eMidorikawa

    2014-10-01

    Full Text Available As dementia progresses, the cognitive functioning of patients declines, and caregivers and other support staff gradually lose the means to communicate with them. However, some caregivers believe that patients can still recognize their surroundings even when they become akinetic with mutism. In this study, we observed eye-movements (preferential looking paradigm to detect the presence of residual cognitive functions in a patient with severe frontotemporal dementia. The subject was a 76-year-old female. At the time of observation, she had lost all spontaneous activities. Magnetic resonance imaging (MRI imaging showed dense atrophy in the bilateral frontotemporal lobe, but the parieto–occipital lobe was preserved. A preferential looking paradigm was used in the experiment whereby two different faces (learned and non-learned were simultaneously presented to the patient on a TV monitor. As a result, we found no significant differences in looking time between the two faces. However, when the saccade timing to the presented faces was examined, a much longer latency was observed for the right rather than the left side of the target faces. Even though the patient had lost all capacity for spontaneous activity, we were able to observe partial residual cognitive ability using the eye-movement paradigm.

  19. Quantitative balance and gait measurement in patients with frontotemporal dementia and Alzheimer diseases: A pilot study

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    Selva Ganapathy Velayutham

    2017-01-01

    Full Text Available Introduction: Alzhiemers disease and Frontotemporal dementia are common neurodegenerative dementias with a wide prevalence. Falls are a common cause of morbidity in these patients. Identifying subclinical involvement of these parameters might serve as a tool in differential analysis of these distinct parameters involved in these conditions and also help in planning preventive strategies to prevent falls. Patients and Methods: Eight patients in age and gender matched patients in each group were compared with normal controls. Standardizes methods of gait and balance aseesment were done in all persons. Results: Results revealed subclinical involvement of gait and balancesin all groups specially during divided attention. The parameters were significantly more affected in patients. Patients with AD and FTD had involement of over all ambulation index balance more affected in AD patients FTD patients showed step cycle, stride length abnormalities. Discussion: There is balance and gait involvement in normal ageing as well as patients with AD and FTD. The pattern of involvement in AD correlates with WHERE pathway involvement and FTD with frontal subcortical circuits involvement. Conclusion: Identification the differential patterns of involvement in subclinical stage might help to differentiate normal ageing and the different types of cortical dementias. This could serve as an additional biomarker and also assist in initiating appropriate training methods to prevent future falls.

  20. Frontotemporal dementia and its subtypes

    DEFF Research Database (Denmark)

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A

    2014-01-01

    BACKGROUND: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel gene...

  1. Kissing or "osculation" in frontotemporal dementia.

    Science.gov (United States)

    Mendez, Mario F; Shapira, Jill S

    2014-01-01

    The authors investigated the neuropsychiatry of kissing in frontotemporal dementia. Among 15 patients, two had compulsive social kissing, bitemporal involvement, and Klüver-Bucy symptoms, and four pursued kissing with sexually disinhibited behavior. Future research should clarify the neuropsychiatric significance of kissing behavior.

  2. Responding to safety issues in frontotemporal dementias.

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    Talerico, K A; Evans, L K

    2001-06-01

    As frontotemporal dementia progresses in individuals, safety issues related to behaviors and injury become a paramount concern. In addition to self-care deficits, frontotemporal dementias are often characterized by behavioral manifestations that include aggression and disinhibition. These behaviors may place the patient and caregivers at risk of injury, stress, and social embarrassment, and frequently lead to institutionalization. Additionally, motor disturbances associated with frontotemporal dementias may contribute to risk of injury from falls. The authors present an integrated biopsychosocial model to guide assessment of needs that may be expressed through behavior. Environmental, behavioral, and psychosocial strategies to assist caregivers in preventing and responding to behaviors and risks are discussed, with the goal of promoting maximum function and quality of life and minimizing caregiver strain. The authors discuss the dangers of physical restraints, which are commonly suggested as a response to fall risk and behavioral symptoms without an awareness of research-based data regarding their lack of efficacy. Benefits and risks of a variety of need-based interventions are presented in a practical, clinically relevant manner. The discussion of diverse safety-enhancing interventions is intended to enable clinicians and caregivers to identify individualized care strategies for patients with frontotemporal dementia.

  3. C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients.

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    Carol Dobson-Stone

    Full Text Available A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD. However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190, to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in 'non-expansion' patients (those with <30 repeats. The C9ORF72 repeat expansion was detected in 5-17% of patients (21-41% of familial FTD patients. For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine 'expansion-positive' patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an 'intermediate' allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of 'non-expansion' FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.

  4. Burdening Care: A Study on Informal Caregivers of Frontotemporal Dementia Patients

    NARCIS (Netherlands)

    S.R. Riedijk (Samantha)

    2009-01-01

    textabstractFrontotemporal dementia (FTD) is a degenerative disease of the brain. The frontal areas of the brain that are affected by degeneration of neurones and accumulation of tau and other inclusion material control personality, social conduct, speech and language, organization and reasoning.

  5. Burdening Care: A Study on Informal Caregivers of Frontotemporal Dementia Patients

    NARCIS (Netherlands)

    S.R. Riedijk (Samantha)

    2009-01-01

    textabstractFrontotemporal dementia (FTD) is a degenerative disease of the brain. The frontal areas of the brain that are affected by degeneration of neurones and accumulation of tau and other inclusion material control personality, social conduct, speech and language, organization and reasoning. In

  6. Evaluation of patients with behavioral and cognitive complaints: Misdiagnosis in frontotemporal dementia and Alzheimer's disease

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    Bárbara Costa Beber

    Full Text Available ABSTRACT Background: Frontotemporal dementia (FTD is a heterogeneous clinicopathological syndrome whose early diagnosis is critical for developing management strategies. Objective: To analyze the variables associated with misdiagnosis in a group of patients with FTD, Alzheimer's disease (AD, and without neurodegenerative disorders (WND, all of whom were evaluated for behavioral and cognitive complaints. Methods: A case-control study with FTD (n=10, probable AD (n=10 and WND (n=10 patients was carried out. The studied variables were disease duration, reason for referral, former diagnosis, behavioral and cognitive symptoms at evaluation, MMSE at the specialist evaluation, and follow-up outcome. The data were analyzed by ANOVA with Bonferroni post-hoc and by Pearson's Chi-Square tests. Results: FTD patients and WND patients showed longer disease duration than AD patients; the main reasons for referral in the FTD group were behavioral, memory and memory plus language problems while all AD and 90% of the WND group were referred for memory. The FTD group had the highest rate of misdiagnosis and worst outcomes after the 12-month follow-up. The majority of AD and WND patients had memory symptoms, while FTD patients presented language (30%, memory and/or language (40% problems on the evaluation. Conclusion: Difficulty in recognizing the main features of FTD and psychiatric disorders with memory impairment was observed. Clinicians tended to generalize memory complaints toward a single diagnosis, identifying almost all these patients as AD or leaving them undiagnosed.

  7. Mentalising music in frontotemporal dementia.

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    Downey, Laura E; Blezat, Alice; Nicholas, Jennifer; Omar, Rohani; Golden, Hannah L; Mahoney, Colin J; Crutch, Sebastian J; Warren, Jason D

    2013-01-01

    Despite considerable recent interest, the biological basis and clinical diagnosis of behavioural variant frontotemporal dementia (bvFTD) pose unresolved problems. Mentalising (the cognitive capacity to interpret the behaviour of oneself and others in terms of mental states) is impaired as a prominent feature of bvFTD, consistent with involvement of brain regions including ventro-medial prefrontal cortex (PFC), orbitofrontal cortex and anterior temporal lobes. Here, we investigated mentalising ability in a cohort of patients with bvFTD using a novel modality: music. We constructed a novel neuropsychological battery requiring attribution of affective mental or non-mental associations to musical stimuli. Mentalising performance of patients with bvFTD (n = 20) was assessed in relation to matched healthy control subjects (n = 20); patients also had a comprehensive assessment of behaviour and general neuropsychological functions. Neuroanatomical correlates of performance on the experimental tasks were investigated using voxel-based morphometry of patients' brain magnetic resonance imaging (MRI) scans. Compared to healthy control subjects, patients showed impaired ability to attribute mental states but not non-mental characteristics to music, and this deficit correlated with performance on a standard test of social inference and with carer ratings of patients' empathic capacity, but not with other potentially relevant measures of general neuropsychological function. Mentalising performance in the bvFTD group was associated with grey matter changes in anterior temporal lobe and ventro-medial PFC. These findings suggest that music can represent surrogate mental states and the ability to construct such mental representations is impaired in bvFTD, with potential implications for our understanding of the biology of bvFTD and human social cognition more broadly. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Frontotemporal dementia and neurocysticercosis: a case report

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    Corina Satler

    Full Text Available ABSTRACT We report a case of a 67-year-old woman with frontotemporal dementia (FTD and a history of neurocysticercosis. After her retirement she showed progressive behavioral changes and neuropsychiatric symptoms with relative preservation of cognitive functioning. During the next three years, the patient manifested progressive deterioration of verbal communication gradually evolving to mutism, a hallmark of cases of progressive nonfluent aphasia.

  9. Autonomic dysfunction: A comparative study of patients with Alzheimer's and frontotemporal dementia – A pilot study

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    Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Gupta, Neelesh; Rukmani, Malligurki Raghurama; Deepika, S.; Sathyaprabha, T. N.

    2017-01-01

    Introduction: In frontotemporal dementia (FTD) and Alzheimer's disease (AD), central autonomic structures get affected early. An insight into autonomic functions in these patients is likely to be of diagnostic importance and thus help in prognosticating and also probably explain unexplained sudden death in some of these patients. Objectives: The objective of this study is to identify autonomic dysfunction prevailing in patients. Then, if there is dysfunction, is the pattern same or different in these two conditions. And if different it will serve as an additional biomarker for specific diagnosis. Patients and Methods: There were 25 patients and 25 controls and six patients and three controls in AD and FTD groups, respectively. The participants who were recruited were assessed for heart rate variability and conventional cardiac autonomic function testing. The parameters were analyzed using LabChart version 7 software and compared with control population using appropriate statistical methods using SPSS version 22 software. Results: The mean overall total power was low in the FTD group (P yoga. The presence of parasympathetic suppression in AD in addition helps differentiate these two conditions. PMID:28149088

  10. Behavioral variant frontotemporal dementia patients do not succumb to the Allais paradox

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    Maxime eBertoux

    2014-09-01

    Full Text Available The Allais Paradox represents on of the earliest empirical challenges to normative models of decision-making, and suggests that choices in one part of a gamble may depend on the possible outcome in another, independent, part of the gamble—a violation of the so-called independence axiom. To account for Allaisian behavior, one well-known class of models propose that individuals’ choices are influenced not only by possible outcomes resulting from one’s choices, but also the anticipation of regret for foregone options. Here we test the regret hypothesis using a population of patients with behavioral variant frontotemporal dementia (bvFTD, a clinical population known to present ventromedial prefrontal cortex dysfunctions and associated with impaired regret processing in previous studies of decision-making. Compared to behavior of matched controls and Alzheimer (AD patients that has no ventromedial prefrontal atrophy, we found a striking diminution of Allaisian behavior among bvFTD patients. These results are consistent with the regret hypothesis and furthermore suggest a crucial role for prefrontal regions in choices that typically stands in contradiction with a basic axiom of rational decision-making.

  11. Effectiveness of Electroconvulsive Therapy for Depression and Cotard’s Syndrome in a Patient with Frontotemporal Lobe Dementia

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    Toshiyuki Kobayashi

    2012-01-01

    Full Text Available In the field of psychogeriatrics, the differential diagnosis of depression and dementia, as well as the treatment of depression and comorbid dementia, is an important issue. In this paper, the authors present the case of a 72-year-old woman with Cotard’s syndrome and frontotemporal dementia (FTD who was admitted to a psychiatric hospital with delusions of negation accompanied by depressive symptoms. Pharmacotherapy over a 2-year hospitalization was unsuccessful, and she was subsequently transferred to our university hospital. A total of 18 sessions of electroconvulsive therapy released her from psychomotor inhibition, appetite loss, and Cotard’s delusions. The indication for electroconvulsive therapy in patients with dementia is discussed.

  12. Autonomic dysfunction: A comparative study of patients with Alzheimer's and frontotemporal dementia – A pilot study

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    Thomas Gregor Issac

    2017-01-01

    Full Text Available Introduction: In frontotemporal dementia (FTD and Alzheimer's disease (AD, central autonomic structures get affected early. An insight into autonomic functions in these patients is likely to be of diagnostic importance and thus help in prognosticating and also probably explain unexplained sudden death in some of these patients. Objectives: The objective of this study is to identify autonomic dysfunction prevailing in patients. Then, if there is dysfunction, is the pattern same or different in these two conditions. And if different it will serve as an additional biomarker for specific diagnosis. Patients and Methods: There were 25 patients and 25 controls and six patients and three controls in AD and FTD groups, respectively. The participants who were recruited were assessed for heart rate variability and conventional cardiac autonomic function testing. The parameters were analyzed using LabChart version 7 software and compared with control population using appropriate statistical methods using SPSS version 22 software. Results: The mean overall total power was low in the FTD group (P < 0.001, and there was significant reduction in the standard deviation of normal-to-normal intervals and root mean square of successive differences (P < 0.001 with elevated sympathovagal balance in the FTD group (P = 0.04. Patients with AD also showed sympathetic dominance, but there was in addition parasympathetic suppression unlike in the FTD group. Conclusion: This study reveals autonomic dysfunction in patients with FTD and AD. Both conditions show sympathetic dominance, probably consecutive to the involvement of central autonomic regulatory structures as a shared domain. It remains to be confirmed if these findings are the cause or effect of neurodegeneration and might open up newer territories of research based on the causal role of neurotransmitters in these regions and thus lead to novel therapeutic options such as yoga. The presence of parasympathetic

  13. Pure word deafness and pure anarthria in a patient with frontotemporal dementia.

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    Iizuka, O; Suzuki, K; Endo, K; Fujii, T; Mori, E

    2007-04-01

    A 66-year-old right-handed man developed pure anarthria following pure word deafness. In addition to language disorders, his behavior gradually changed and finally included violence against his wife. Brain magnetic resonance imagings revealed atrophy of the left perisylvian area, which included the inferior half of the precentral gyrus and the upper portion of the superior temporal gyrus, consistent with frontotemporal dementia (FTD). It has been documented as either a disorder of expressive language or as an impaired understanding of word meaning. Unlike with pure anarthria, pure word deafness is not included in the clinical diagnostic current criteria for FTD. However, a large variety of language symptoms can appear in FTD according to the distribution of pathological changes in the frontotemporal cortices. This case suggests that pure word deafness could be a prodomal symptom of FTD.

  14. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia

    OpenAIRE

    Rascovsky, Katya; Hodges, John R.; Knopman, David; Mario F. Mendez; Kramer, Joel H.; Neuhaus, John; John C. van Swieten; Seelaar, Harro; Elise G P Dopper; Onyike, Chiadi U.; Hillis, Argye E.; Josephs, Keith A.; Boeve, Bradley F.; Kertesz, Andrew; Seeley, William W.

    2011-01-01

    Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia ...

  15. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia

    OpenAIRE

    Rascovsky, Katya; Hodges, John R.; Knopman, David; Mario F. Mendez; Kramer, Joel H.; Neuhaus, John; van Swieten, John C.; Seelaar, Harro; Dopper, Elise G.P.; Onyike, Chiadi U.; Argye E. Hillis; Josephs, Keith A.; Boeve, Bradley F.; Kertesz, Andrew; Seeley, William W.

    2011-01-01

    Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia ...

  16. The role of the orbitofrontal cortex in regulation of interpersonal space: evidence from frontal lesion and frontotemporal dementia patients.

    Science.gov (United States)

    Perry, Anat; Lwi, Sandy J; Verstaen, Alice; Dewar, Callum; Levenson, Robert W; Knight, Robert T

    2016-12-01

    Interpersonal distance is central to communication and complex social behaviors but the neural correlates of interpersonal distance preferences are not defined. Previous studies suggest that damage to the orbitofrontal cortex (OFC) is associated with impaired interpersonal behavior. To examine whether the OFC is critical for maintaining appropriate interpersonal distance, we tested two groups of patients with OFC damage: Patients with OFC lesions and patients with behavioral variant frontotemporal dementia. These two groups were compared to healthy controls and to patients with lesions restricted to the dorsolateral prefrontal cortex. Only patients with OFC damage showed abnormal interpersonal distance preferences, which were significantly different from both controls and patients with dorsolateral prefrontal damage. The comfortable distances these patients chose with strangers were significantly closer than the other groups and resembled distances normally used with close others. These results shed light on the role of the OFC in regulating social behavior and may serve as a simple diagnostic tool for dementia or lesion patients.

  17. Studying social cognition in patients with schizophrenia and patients with frontotemporal dementia: theory of mind and the perception of sarcasm.

    Science.gov (United States)

    Kosmidis, Mary H; Aretouli, Eleni; Bozikas, Vassilis P; Giannakou, Maria; Ioannidis, Panayiotis

    2008-01-01

    We investigated social cognition and theory of mind in patients with schizophrenia and in patients with frontotemporal dementia in order to elucidate the cognitive mechanisms involved in the breakdown of these skills in psychiatric and neurological patients. Our tasks included videotaped scenarios of social interactions depicting sincere, sarcastic and paradoxical remarks, as well as lies. We found impaired performance of the schizophrenia group on all theory of mind conditions despite their intact understanding of sincere statements. In contrast, the FTD group performed poorly only when they had to rely on paralinguistic cues indicating sarcasm or lies, and not on paradoxical remarks or sarcasm when given additional verbal cues. Our findings suggest that, while current deficits in social and interpersonal functioning in patients with FTD may reflect a decrement in previously acquired skills, similar deficits in patients with schizophrenia may reflect an altogether inadequately learned process.

  18. Studying Social Cognition in Patients with Schizophrenia and Patients with Frontotemporal Dementia: Theory of Mind and the Perception of Sarcasm

    Directory of Open Access Journals (Sweden)

    Mary H. Kosmidis

    2008-01-01

    Full Text Available We investigated social cognition and theory of mind in patients with schizophrenia and in patients with frontotemporal dementia in order to elucidate the cognitive mechanisms involved in the breakdown of these skills in psychiatric and neurological patients. Our tasks included videotaped scenarios of social interactions depicting sincere, sarcastic and paradoxical remarks, as well as lies. We found impaired performance of the schizophrenia group on all theory of mind conditions despite their intact understanding of sincere statements. In contrast, the FTD group performed poorly only when they had to rely on paralinguistic cues indicating sarcasm or lies, and not on paradoxical remarks or sarcasm when given additional verbal cues. Our findings suggest that, while current deficits in social and interpersonal functioning in patients with FTD may reflect a decrement in previously acquired skills, similar deficits in patients with schizophrenia may reflect an altogether inadequately learned process.

  19. Genetics Home Reference: frontotemporal dementia with parkinsonism-17

    Science.gov (United States)

    ... dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain. 2003 Sep;126(Pt 9):2016-22. Epub 2003 Jul 22. Citation on PubMed Spillantini MG, Van Swieten JC, Goedert M. Tau gene mutations in frontotemporal dementia and parkinsonism linked ...

  20. Cortical function in Alzheimer’s disease and frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Wang Pan

    2016-01-01

    Full Text Available Alzheimer’s disease (AD and the behavioral variant of frontotemporal dementia (bvFTD are the most common causes of dementia; however, their overlapping clinical syndromes and involved brain regions make a differential diagnosis difficult. We aimed to identify the differences in the cognition and motor cortex excitability between AD and bvFTD patients.

  1. Research progress of behavioral variant frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Xiao-hua GU

    2015-07-01

    Full Text Available There is no epidemiological data of frontotemporal dementia (FTD in China. The application of updated diagnostic criteria, publishing of frontotemporal lobar degeneration (FTLD consensus in China, development of multimodal imaging and biomarkers promote the clinical understanding on behavioral variant frontotemporal dementia (bvFTD. There is still no drugs treating FTD approved by U.S. Food and Drug Administration (FDA. Multidisciplinary intervention may delay the progression of bvFTD. DOI: 10.3969/j.issn.1672-6731.2015.07.006

  2. Phenotypic heterogeneity of monogenic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Alberto eBenussi

    2015-09-01

    Full Text Available Frontotemporal dementia (FTD is a genetically and pathologically heterogeneous disorder characterized by personality changes, language impairment and deficits of executive functions associated with frontal and temporal lobe degeneration. Different phenotypes have been defined on the basis of presenting clinical symptoms, i.e. the behavioral variant of FTD (bvFTD, the agrammatic variant of Primary Progressive Aphasia (avPPA and the semantic variant of PPA (svPPA. Some patients have an associated movement disorder, either parkinsonism, as in Progressive Supranuclear Palsy (PSP and Corticobasal Syndrome (CBS, or motor neuron disease (FTD-MND. A family history of dementia is found in 40% of cases of FTD and about 10% have a clear autosomal dominant inheritance. Genetic studies have identified several genes associated to monogenic FTD: microtubule-associated protein tau (MAPT, progranulin (GRN, TAR DNA-binding protein 43 (TARBDP, valosin-containing protein (VCP, charged multivesicular body protein 2B (CHMP2B, fused in sarcoma (FUS and the hexanucleotide repeat expansion in intron 1 of the chromosome 9 open reading frame 72 (C9orf72. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation. The objective of the present work is to review and evaluate available literature data in order to highlight recent advances in clinical, biological and neuroimaging features of monogenic frontotemporal lobar degeneration and try to identify different mechanisms underlying the extreme phenotypic heterogeneity that characterizes this disease.

  3. Presymptomatic studies in genetic frontotemporal dementia.

    Science.gov (United States)

    Rohrer, J D; Warren, J D; Fox, N C; Rossor, M N

    2013-10-01

    Approximately 20% of patients with the neurodegenerative disorder frontotemporal dementia (FTD) have an autosomal dominant pattern of inheritance. Genetic FTD is caused by mutations in three genes in most cases (progranulin, microtubule-associated protein tau and chromosome 9 open reading frame 72) although a number of other genes are rare causes. Studies of other neurodegenerative diseases have shown imaging and biomarker evidence of disease onset many years prior to the development of symptoms. Similar studies in genetic FTD are now revealing evidence of a series of presymptomatic changes, initially in plasma biomarkers followed by MR imaging abnormalities of functional and structural connectivity and then grey matter atrophy. Lastly, neuropsychometric tests become abnormal in proximity to the onset of symptoms. Such studies have been relatively small until now but research centres with an expertise in genetic FTD are now forming consortia such as the Genetic Frontotemporal Dementia Initiative (GenFI) to create larger cohorts that can form the basis of future clinical trials. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Genetics Home Reference: CHMP2B-related frontotemporal dementia

    Science.gov (United States)

    ... Conditions CHMP2B-related frontotemporal dementia CHMP2B-related frontotemporal dementia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description CHMP2B -related frontotemporal dementia is a progressive brain disorder that affects personality, ...

  5. Memory Test Performance on Analogous Verbal and Nonverbal Memory Tests in Patients with Frontotemporal Dementia and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Deanna Baldock

    2016-01-01

    Full Text Available Background: Patients with frontotemporal dementia (FTD typically have initial deficits in language or changes in personality, while the defining characteristic of Alzheimer's disease (AD is memory impairment. Neuropsychological findings in the two diseases tend to differ, but can be confounded by verbal impairment in FTD impacting performance on memory tests in these patients. Methods: Twenty-seven patients with FTD and 102 patients with AD underwent a neuropsychological assessment before diagnosis. By utilizing analogous versions of a verbal and nonverbal memory test, we demonstrated differences in these two modalities between AD and FTD. Discussion: Better differentiation between AD and FTD is found in a nonverbal memory test, possibly because it eliminates the confounding variable of language deficits found in patients with FTD. These results highlight the importance of nonverbal learning tests with multiple learning trials in diagnostic testing.

  6. Frontotemporal dementia caused by CHMP2B mutations

    DEFF Research Database (Denmark)

    Isaacs, A M; Johannsen, P; Holm, I;

    2011-01-01

    CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient. ...... features of FTD caused by CHMP2B truncation mutations as well as new brain imaging and neuropathological findings. Finally, we collate the current data on CHMP2B missense mutations, which have been reported in FTD and motor neuron disease....

  7. No association of common VCP variants with sporadic frontotemporal dementia.

    Science.gov (United States)

    Schumacher, Axel; Friedrich, Patricia; Diehl, Janine; Ibach, Bernd; Schoepfer-Wendels, Andreas; Mueller, Jakob C; Konta, Lidija; Laws, Simon M; Kurz, Alexander; Foerstl, Hans; Riemenschneider, Matthias

    2009-02-01

    Mutations in the gene for valosin containing protein (VCP) cause autosomal dominant inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD). To investigate the role of this novel gene in sporadic forms of frontotemporal dementia (FTD), we genotyped 27 single nucleotide polymorphisms covering the entire VCP genomic region in 198 patients with sporadic FTD and 184 matched controls from Germany. No significant association could be demonstrated. There is no evidence, that common variants in VCP confer a strong risk to the development of sporadic FTD.

  8. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: A cross-sectional study

    NARCIS (Netherlands)

    E. Majounie (Elisa); A. Renton (Alan); K. Mok (Kin); E.G.P. Dopper (Elise); A. Waite (Adrian); S. Rollinson (Sara); A. Chiò (Adriano); G. Restagno (Gabriella); N. Nicolaou (Nayia); J. Simón-Sánchez (Javier); J.C. van Swieten (John); Y. Abramzon (Yevgeniya); J. Johnson (Janel); M. Sendtner (Michael); R. Pamphlett (Roger); R. Orrell (Richard); S. Mead (Simon); K.C. Sidle (Katie); H. Houlden (Henry); J.D. Rohrer (Jonathan Daniel); K.E. Morrison (Karen); H. Pall (Hardev); D. Talbot; O. Ansorge (Olaf); D.G. Hernandez (Dena); S. Arepalli (Sampath); M. Sabatelli (Mario); G. Mora (Gabriele); J.C. Corbo (Joseph); F. Giannini (Fabio); A. Calvo (Andrea); E. Englund (Elisabet); G. Borghero (Giuseppe); O.A.M. Floris; A. Remes (Anne); H. Laaksovirta (Hannu); L. McCluskey (Leo); J.Q. Trojanowski (John); V.M. Deerlin (Vivianna); G.D. Schellenberg (Gerard); M.A. Nalls (Michael); V.E. Drory (Vivian E); C.S. Lu (Chin-Song); T.-H. Yeh (Tu-Hsueh); H. Ishiura (Hiroyuki); Y. Takahashi (Yukari); S. Tsuji (Shoji); I. Le Ber (Isabelle); A. Brice; C. Drepper (Carsten); N. Williams (Nigel); J. Kirby (Janine); P.J. Shaw (Pamela); J. Hardy (John); P.J. Tienari (Pentti); P. Heutink (Peter); H. Morris (Huw); S. Pickering-Brown (Stuart); B.J. Traynor (Bryan)

    2012-01-01

    textabstractBackground: We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods: We screened 4448 patients diagnosed with

  9. The Genetics of Monogenic Frontotemporal Dementia

    Directory of Open Access Journals (Sweden)

    Leonel T. Takada

    Full Text Available ABSTRACTAround 10-15% of patients diagnosed with frontotemporal dementia (FTD have a positive family history for FTD with an autosomal dominant pattern of inheritance. Since the identification of mutations in MAPT(microtubuleassociated protein tau gene in 1998, over 10 other genes have been associated with FTD spectrum disorders, discussed in this review. Along with MAPT, mutations in GRN(progranulin and C9orf72(chromosome 9 open reading frame 72 are the most commonly identified in FTD cohorts. The association of FTD and motor neuron disease (MND can be caused by mutations in C9orf72and other genes, such as TARDBP(TAR DNA-binding protein, FUS(fused in sarcoma, UBQLN2(ubiquilin 2. Multisystem proteinopathy is a complex phenotype that includes FTD, Paget disease of the bone, inclusion body myopathy and MND, and can be due to mutations in VCP(valosing containing protein and other recently identified genes.

  10. Frontotemporal dementias: Recent advances and current controversies

    OpenAIRE

    Leyton Cristian; Hodges John

    2010-01-01

    Frontotemporal dementia (FTD) syndromes comprise a heterogeneous group of neurodegenerative conditions characterized by atrophy in the frontal and temporal lobes. Three main clinical variants are recognized: Behavioral variant (bv-FTD), Semantic dementia (SD), and Progressive nonfluent aphasia (PNFA). However, logopenic/phonological (LPA) variant has been recently described, showing a distinctive pattern of brain atrophy and often associated to Alzheimer′s disease pathology. The diagno...

  11. Individual Music Therapy with Persons with Frontotemporal Dementia

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner; Aldridge, David

    2005-01-01

    It is possible to slow down the progression of Alzheimer’s disease with pharmacological treatment. When this treatment is given to people with types of dementia that affect the frontal and temporal lobes (Frontotemporal Dementia) the results are discouraging. It is observed that the patients show...... is an integration of a relational music therapy approach and a more physiologically based arousal model, and is here illustrated in a case study research that integrated both qualitative and quantitative data in a flexible research design.......It is possible to slow down the progression of Alzheimer’s disease with pharmacological treatment. When this treatment is given to people with types of dementia that affect the frontal and temporal lobes (Frontotemporal Dementia) the results are discouraging. It is observed that the patients show...

  12. Individual Music Therapy with Persons with Frontotemporal Dementia

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    2007-01-01

    It is possible to slow down the progression of Alzheimer's disease with pharmacological treatment. When this treatment is given to people with types of dementia that affect the frontal and temporal lobes (Frontotemporal Dementia) the results are discouraging. It is observed that the patients show...... is an integration of a relational music therapy approach and a more physiologically based arousal model, and is here illustrated in a case study that integrated both qualitative and quantitative data in a flexible research design1 .......It is possible to slow down the progression of Alzheimer's disease with pharmacological treatment. When this treatment is given to people with types of dementia that affect the frontal and temporal lobes (Frontotemporal Dementia) the results are discouraging. It is observed that the patients show...

  13. Characterizing Sexual Behavior in Frontotemporal Dementia.

    Science.gov (United States)

    Ahmed, Rebekah M; Kaizik, Cassandra; Irish, Muireann; Mioshi, Eneida; Dermody, Nadene; Kiernan, Matthew C; Piguet, Olivier; Hodges, John R

    2015-01-01

    Frontotemporal dementia (FTD) is characterized by a number of prominent behavioral changes. While FTD has been associated with the presence of aberrant or unusual sexual behaviors in a proportion of patients, few studies have formally investigated changes in sexual function in this disease. We aimed to systematically quantify changes in sexual behavior, including current symptoms and changes from prior diagnoses, in behavioral-variant (bvFTD) and semantic dementia (SD), compared to Alzheimer's disease (AD). Carers of 49 dementia patients (21 bvFTD, 11 SD, 17 AD) were interviewed using the Sexual Behavior and Intimacy Questionnaire (SIQ), a survey designed to assess changes in sexual function across multiple domains including initiating, level of affection, and aberrant or unusual sexual behavior. BvFTD patients show prominent hyposexual behavior including decreased affection, initiation, and response to advances by partners, and decreased frequency of sexual relations, compared to AD and to SD patients. The greatest changes in sexual behavior compared to pre-diagnoses were found in the bvFTD group with a 90-100% decrease in initiation, response, and frequency of sexual relations. Notably, aberrant or unusual sexual behavior was reported in a minority of bvFTD and SD patients and occurred in patients who also showed hyposexual behavior toward their partner. Overall loss of affection, reduced initiation of sexual activity, and responsiveness is an overwhelming feature of bvFTD. In contrast, aberrant or unusual sexual behavior is observed in the minority of bvFTD patients. The underlying pathophysiology of these changes likely reflects structural and functional changes in frontoinsular and limbic regions including the hypothalamus.

  14. Frontotemporal dementia: Change of familial caregiver burden and partner relation in a Dutch cohort of 63 patients

    NARCIS (Netherlands)

    S.R. Riedijk (Samantha); H.J. Duivenvoorden (Hugo); S.M. Rosso (Sonia); J.C. van Swieten; M.F. Niermeijer (Martinus); A. Tibben (Arend)

    2008-01-01

    textabstractBackground/Aims: The current study examined the change of caregiver burden and the development of the quality of the partner relation in frontotemporal dementia (FTD). Methods: During a 2-year period, deterioration, behavioural problems, caregiver burden, general psychopathology, quality

  15. Personality Traits in the Siblings and Children of Patients with Frontotemporal Dementia: A Questionnaire-based Study

    Science.gov (United States)

    Korada, Suresh Kumar; Chandra, Sadanandavalli Retnaswami; Benegal, Vivek; Purushothaman, Meera; Philip, Mariamma

    2017-01-01

    Introduction: Frontotemporal dementias (FLD) form a group of relatively young onset, male dominant dementias with significant behavioral abnormalities early in the course of the disease. Routine assessment suggested preexisting traits such as lack of empathy, self-directedness, and persistence in most of these persons even before the onset of disease. Hence, we decided the study, the siblings and children of patients for any specific traits and correlation with hexanucleotide expansion repeats if any traits were identified. Patients and Methods: A total of 35 age- and gender-matched cases and controls were included for the study as per criteria. They were screened for mental illness and cognitive dysfunction using Hindi Mental State Examination and Mini-mental State Examination. Eligible persons were given temperament and character inventory (TCI) scores for the recommended parameters. Hexanucleotide expansion was also studied in the patients, cases and controls. Results: No specific personality trait was found to have an increased correlation with siblings and children of patients with FLD in this small group using TCI scores. Conclusions: 7% of cases showed Hexanucleotide expansion suggesting a possible risk. The role of self reporting bias resulting in normal personality trait needs to be addressed in future studies. PMID:28250555

  16. Mutation Frequency of the Major Frontotemporal Dementia Genes, MAPT, GRN and C9ORF72 in a Turkish Cohort of Dementia Patients

    Science.gov (United States)

    Guven, Gamze; Lohmann, Ebba; Bras, Jose; Gibbs, J. Raphael; Gurvit, Hakan; Bilgic, Basar; Hanagasi, Hasmet; Rizzu, Patrizia; Heutink, Peter; Emre, Murat; Erginel-Unaltuna, Nihan; Just, Walter; Hardy, John; Singleton, Andrew; Guerreiro, Rita

    2016-01-01

    ‘Microtubule-associated protein tau’ (MAPT), ‘granulin’ (GRN) and ‘chromosome 9 open reading frame72’ (C9ORF72) gene mutations are the major known genetic causes of frontotemporal dementia (FTD). Recent studies suggest that mutations in these genes may also be associated with other forms of dementia. Therefore we investigated whether MAPT, GRN and C9ORF72 gene mutations are major contributors to dementia in a random, unselected Turkish cohort of dementia patients. A combination of whole-exome sequencing, Sanger sequencing and fragment analysis/Southern blot was performed in order to identify pathogenic mutations and novel variants in these genes as well as other FTD-related genes such as the ‘charged multivesicular body protein 2B’ (CHMP2B), the ‘FUS RNA binding protein’ (FUS), the ‘TAR DNA binding protein’ (TARDBP), the ‘sequestosome1’ (SQSTM1), and the ‘valosin containing protein’ (VCP). We determined one pathogenic MAPT mutation (c.1906C>T, p.P636L) and one novel missense variant (c.38A>G, p.D13G). In GRN we identified a probably pathogenic TGAG deletion in the splice donor site of exon 6. Three patients were found to carry the GGGGCC expansions in the non-coding region of the C9ORF72 gene. In summary, a complete screening for mutations in MAPT, GRN and C9ORF72 genes revealed a frequency of 5.4% of pathogenic mutations in a random cohort of 93 Turkish index patients with dementia. PMID:27632209

  17. Frontotemporal dementias: Recent advances and current controversies

    Directory of Open Access Journals (Sweden)

    Leyton Cristian

    2010-10-01

    Full Text Available Frontotemporal dementia (FTD syndromes comprise a heterogeneous group of neurodegenerative conditions characterized by atrophy in the frontal and temporal lobes. Three main clinical variants are recognized: Behavioral variant (bv-FTD, Semantic dementia (SD, and Progressive nonfluent aphasia (PNFA. However, logopenic/phonological (LPA variant has been recently described, showing a distinctive pattern of brain atrophy and often associated to Alzheimer′s disease pathology. The diagnosis of FTD is challenging, since there is clinical, pathological, and genetic overlap between the variants and other neurodegenerative diseases, such as motoneuron disease (MND and corticobasal degeneration (CBD. In addition, patients with gene mutations (tau and progranulin display an inconsistent clinical phenotype and the correspondence between the clinical variant and its pathology is unpredictable. New cognitive tests based on social cognition and emotional recognition together with advances in molecular pathology and genetics have contributed to an improved understanding. There is now a real possibility of accurate biomarkers for early diagnosis. The present review concentrates on new insights and debates in FTD.

  18. TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    van der Zee, Julie; Gijselinck, Ilse; Van Mossevelde, Sara; Perrone, Federica; Dillen, Lubina; Heeman, Bavo; Bäumer, Veerle; Engelborghs, Sebastiaan; De Bleecker, Jan; Baets, Jonathan; Gelpi, Ellen; Rojas-García, Ricardo; Clarimón, Jordi; Lleó, Alberto; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Perneczky, Robert; Synofzik, Matthis; Just, Jennifer; Schöls, Ludger; Graff, Caroline; Thonberg, Håkan; Borroni, Barbara; Padovani, Alessandro; Jordanova, Albena; Sarafov, Stayko; Tournev, Ivailo; de Mendonça, Alexandre; Miltenberger-Miltényi, Gabriel; Simões do Couto, Frederico; Ramirez, Alfredo; Jessen, Frank; Heneka, Michael T; Gómez-Tortosa, Estrella; Danek, Adrian; Cras, Patrick; Vandenberghe, Rik; De Jonghe, Peter; De Deyn, Peter P; Sleegers, Kristel; Cruts, Marc; Van Broeckhoven, Christine; Goeman, Johan; Nuytten, Dirk; Smets, Katrien; Robberecht, Wim; Damme, Philip Van; Bleecker, Jan De; Santens, Patrick; Dermaut, Bart; Versijpt, Jan; Michotte, Alex; Ivanoiu, Adrian; Deryck, Olivier; Bergmans, Bruno; Delbeck, Jean; Bruyland, Marc; Willems, Christiana; Salmon, Eric; Pastor, Pau; Ortega-Cubero, Sara; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Hernández, Isabel; Boada, Mercè; Ruiz, Agustín; Sorbi, Sandro; Nacmias, Benedetta; Bagnoli, Silvia; Sorbi, Sandro; Sanchez-Valle, Raquel; Llado, Albert; Santana, Isabel; Rosário Almeida, Maria; Frisoni, Giovanni B; Maetzler, Walter; Matej, Radoslav; Fraidakis, Matthew J; Kovacs, Gabor G; Fabrizi, Gian Maria; Testi, Silvia

    2017-03-01

    We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS.

  19. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.

    Science.gov (United States)

    Rascovsky, Katya; Hodges, John R; Knopman, David; Mendez, Mario F; Kramer, Joel H; Neuhaus, John; van Swieten, John C; Seelaar, Harro; Dopper, Elise G P; Onyike, Chiadi U; Hillis, Argye E; Josephs, Keith A; Boeve, Bradley F; Kertesz, Andrew; Seeley, William W; Rankin, Katherine P; Johnson, Julene K; Gorno-Tempini, Maria-Luisa; Rosen, Howard; Prioleau-Latham, Caroline E; Lee, Albert; Kipps, Christopher M; Lillo, Patricia; Piguet, Olivier; Rohrer, Jonathan D; Rossor, Martin N; Warren, Jason D; Fox, Nick C; Galasko, Douglas; Salmon, David P; Black, Sandra E; Mesulam, Marsel; Weintraub, Sandra; Dickerson, Brad C; Diehl-Schmid, Janine; Pasquier, Florence; Deramecourt, Vincent; Lebert, Florence; Pijnenburg, Yolande; Chow, Tiffany W; Manes, Facundo; Grafman, Jordan; Cappa, Stefano F; Freedman, Morris; Grossman, Murray; Miller, Bruce L

    2011-09-01

    Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older

  20. Emotional evaluation and memory in behavioral variant frontotemporal dementia

    OpenAIRE

    St. Jacques, Peggy L.; Grady, Cheryl; Davidson, Patrick S. R.; Chow, Tiffany W

    2015-01-01

    Behavioral variant frontotemporal dementia (bvFTD) affects emotional evaluation, but less is known regarding the patients' ability to remember emotional stimuli. Here, bvFTD patients and age-matched controls studied positive, negative, and neutral pictures followed by a recognition memory test. Compared to controls, bvFTD patients showed a reduction in emotional evaluation of negative scenes, but not of positive or neutral scenes. Additionally, the patients showed an overall reduction in reco...

  1. Right Limbic FDG-PET Hypometabolism Correlates with Emotion Recognition and Attribution in Probable Behavioral Variant of Frontotemporal Dementia Patients.

    Science.gov (United States)

    Cerami, Chiara; Dodich, Alessandra; Iannaccone, Sandro; Marcone, Alessandra; Lettieri, Giada; Crespi, Chiara; Gianolli, Luigi; Cappa, Stefano F; Perani, Daniela

    2015-01-01

    The behavioural variant of frontotemporal dementia (bvFTD) is a rare disease mainly affecting the social brain. FDG-PET fronto-temporal hypometabolism is a supportive feature for the diagnosis. It may also provide specific functional metabolic signatures for altered socio-emotional processing. In this study, we evaluated the emotion recognition and attribution deficits and FDG-PET cerebral metabolic patterns at the group and individual levels in a sample of sporadic bvFTD patients, exploring the cognitive-functional correlations. Seventeen probable mild bvFTD patients (10 male and 7 female; age 67.8±9.9) were administered standardized and validated version of social cognition tasks assessing the recognition of basic emotions and the attribution of emotions and intentions (i.e., Ekman 60-Faces test-Ek60F and Story-based Empathy task-SET). FDG-PET was analysed using an optimized voxel-based SPM method at the single-subject and group levels. Severe deficits of emotion recognition and processing characterized the bvFTD condition. At the group level, metabolic dysfunction in the right amygdala, temporal pole, and middle cingulate cortex was highly correlated to the emotional recognition and attribution performances. At the single-subject level, however, heterogeneous impairments of social cognition tasks emerged, and different metabolic patterns, involving limbic structures and prefrontal cortices, were also observed. The derangement of a right limbic network is associated with altered socio-emotional processing in bvFTD patients, but different hypometabolic FDG-PET patterns and heterogeneous performances on social tasks at an individual level exist.

  2. Right Limbic FDG-PET Hypometabolism Correlates with Emotion Recognition and Attribution in Probable Behavioral Variant of Frontotemporal Dementia Patients.

    Directory of Open Access Journals (Sweden)

    Chiara Cerami

    Full Text Available The behavioural variant of frontotemporal dementia (bvFTD is a rare disease mainly affecting the social brain. FDG-PET fronto-temporal hypometabolism is a supportive feature for the diagnosis. It may also provide specific functional metabolic signatures for altered socio-emotional processing. In this study, we evaluated the emotion recognition and attribution deficits and FDG-PET cerebral metabolic patterns at the group and individual levels in a sample of sporadic bvFTD patients, exploring the cognitive-functional correlations. Seventeen probable mild bvFTD patients (10 male and 7 female; age 67.8±9.9 were administered standardized and validated version of social cognition tasks assessing the recognition of basic emotions and the attribution of emotions and intentions (i.e., Ekman 60-Faces test-Ek60F and Story-based Empathy task-SET. FDG-PET was analysed using an optimized voxel-based SPM method at the single-subject and group levels. Severe deficits of emotion recognition and processing characterized the bvFTD condition. At the group level, metabolic dysfunction in the right amygdala, temporal pole, and middle cingulate cortex was highly correlated to the emotional recognition and attribution performances. At the single-subject level, however, heterogeneous impairments of social cognition tasks emerged, and different metabolic patterns, involving limbic structures and prefrontal cortices, were also observed. The derangement of a right limbic network is associated with altered socio-emotional processing in bvFTD patients, but different hypometabolic FDG-PET patterns and heterogeneous performances on social tasks at an individual level exist.

  3. [A nursing experience using the props-integrated communicative approach to ameliorate aggression in a frontotemporal dementia patient].

    Science.gov (United States)

    Shih, Ying-Jyun; Wang, Ya-Hui; Yang, Yung-Jen

    2014-12-01

    This report introduces the nursing caring experience with a male patient with frontotemporal dementia (FTD) who was hospitalized in an acute psychiatric ward from March 5th to April 30th, 2012 due to the clinical manifestations of verbally expressive impairment, aggression, and subsequent caregiver burden. The patient was assessed according to the guidelines of clinical competencies for mental health nursing assessments developed by the Psychiatric Mental Health Nurses Association. Three clinical diagnoses were identified after this assessment, including (1) impaired verbal communication, (2) chronic confusion, and (3) caregiver role strain. The current report focuses only on the clinical issue of impaired verbal communication. We adopted a props-integrated communicative approach by integrating props and physical motions with communicative strategies. This approach enabled us to formulate a patient-centered communicating model and prompt for active expression and adequate communication, which ultimately resolved the patient's aggression problem. In addition, we provided psychoeducation to the family members in order to teach them the relevant knowledge, skills, and approaches that caregivers may use to enhance their caring capabilities and reduce the burden of caregiving. This successful experience may be used as a reference in caring for FTD patients with communicative impairments. Our proposed approach integrates props with simple language and develops an appropriate communicating model to provide high quality care for patients.

  4. Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2017-03-01

    Full Text Available The truncated mutant form of the charged multivesicular body protein 2B (CHMP2B is causative for frontotemporal dementia linked to chromosome 3 (FTD3. CHMP2B is a constituent of the endosomal sorting complex required for transport (ESCRT and, when mutated, disrupts endosome-to-lysosome trafficking and substrate degradation. To understand the underlying molecular pathology, FTD3 patient induced pluripotent stem cells (iPSCs were differentiated into forebrain-type cortical neurons. FTD3 neurons exhibited abnormal endosomes, as previously shown in patients. Moreover, mitochondria of FTD3 neurons displayed defective cristae formation, accompanied by deficiencies in mitochondrial respiration and increased levels of reactive oxygen. In addition, we provide evidence for perturbed iron homeostasis, presenting an in vitro patient-specific model to study the effects of iron accumulation in neurodegenerative diseases. All phenotypes observed in FTD3 neurons were rescued in CRISPR/Cas9-edited isogenic controls. These findings illustrate the relevance of our patient-specific in vitro models and open up possibilities for drug target development.

  5. In vivo cholinergic circuit evaluation in frontotemporal and Alzheimer dementias.

    Science.gov (United States)

    Di Lazzaro, V; Pilato, F; Dileone, M; Saturno, E; Oliviero, A; Marra, C; Daniele, A; Ranieri, F; Gainotti, G; Tonali, P A

    2006-04-11

    The test of short latency afferent inhibition (SAI) of the motor cortex is helpful in demonstrating dysfunction of central cholinergic circuits in Alzheimer disease (AD). The authors evaluated SAI in 20 patients with frontotemporal dementia (FTD) and compared data with those from 20 patients with AD and 20 controls. SAI was normal in FTD, whereas it was reduced in AD. SAI may represent an additional tool to discriminate FTD from AD.

  6. Functional MRI of music emotion processing in frontotemporal dementia.

    Science.gov (United States)

    Agustus, Jennifer L; Mahoney, Colin J; Downey, Laura E; Omar, Rohani; Cohen, Miriam; White, Mark J; Scott, Sophie K; Mancini, Laura; Warren, Jason D

    2015-03-01

    Frontotemporal dementia is an important neurodegenerative disorder of younger life led by profound emotional and social dysfunction. Here we used fMRI to assess brain mechanisms of music emotion processing in a cohort of patients with frontotemporal dementia (n = 15) in relation to healthy age-matched individuals (n = 11). In a passive-listening paradigm, we manipulated levels of emotion processing in simple arpeggio chords (mode versus dissonance) and emotion modality (music versus human emotional vocalizations). A complex profile of disease-associated functional alterations was identified with separable signatures of musical mode, emotion level, and emotion modality within a common, distributed brain network, including posterior and anterior superior temporal and inferior frontal cortices and dorsal brainstem effector nuclei. Separable functional signatures were identified post-hoc in patients with and without abnormal craving for music (musicophilia): a model for specific abnormal emotional behaviors in frontotemporal dementia. Our findings indicate the potential of music to delineate neural mechanisms of altered emotion processing in dementias, with implications for future disease tracking and therapeutic strategies.

  7. Neurofilament light chain: a biomarker for genetic frontotemporal dementia

    OpenAIRE

    Meeter, Lieke H.; Dopper, Elise G.; Jiskoot, Lize C.; Sanchez-Valle, Raquel; Graff, Caroline; Benussi, Luisa; Ghidoni, Roberta; Pijnenburg, Yolande A; Borroni, Barbara; Galimberti, Daniela; Laforce, Robert Jr; Masellis, Mario; Vandenberghe, Rik; Le Ber, Isabelle; Otto, Markus

    2016-01-01

    Abstract Objective To evaluate cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL) levels in genetic frontotemporal dementia (FTD) as a potential biomarker in the presymptomatic stage and during the conversion into the symptomatic stage. Additionally, to correlate NfL levels to clinical and neuroimaging parameters. Methods In this multicenter case?control study, we investigated CSF NfL in 174 subjects (48 controls, 40 presymptomatic carriers and 86 patients with microtubule?as...

  8. Ugly aesthetic perception associated with emotional changes in experience of art by behavioural variant of frontotemporal dementia patients.

    Science.gov (United States)

    Boutoleau-Bretonnière, Claire; Bretonnière, Cédric; Evrard, Christelle; Rocher, Laetitia; Mazzietti, Audric; Koenig, Olivier; Vercelletto, Martine; Derkinderen, Pascal; Thomas-Antérion, Catherine

    2016-08-01

    The aesthetic experience through art is a window into the study of emotions. Patients with behavioural variant of frontotemporal dementia (bvFTD) have early alteration of emotional processing. A new appreciation of art has been reported in some of these patients. We designed a computerized task using 32 abstract paintings that allowed us to investigate the integrity of patients' emotions when viewing the artwork. We evaluated both conscious and explicit appraisal of emotions [aesthetic judgment (beautiful/ugly), emotional relevance (affected or not by the painting), emotional valence (pleasant/unpleasant), emotional reaction (adjective choice) and arousal] and unconscious processing. Fifteen bvFTD patients and 15 healthy controls were included. BvFTD patients reported that they were "little touched" by the paintings. Aesthetic judgment was very different between the two groups: the paintings were considered ugly (negative aesthetic bias) and unpleasant (negative emotional bias) more often by the patients than by controls. Valence and aesthetic judgments correlated in both groups. In addition, there was a positive bias in the implicit task and for explicit emotional responses. Patients frequently chose the word "sad" and rarely expressed themselves with such adjectives as "happy". Our results suggest that bvFTD patients can give an aesthetic judgment, but present abstraction difficulties, as spectators, resulting from impairments in the cognitive processes involved. They also have difficulties in terms of emotional processes with the loss of the ability to feel the emotion per se (i.e., to feel an emotion faced with art) linked to behaviour assessment. This cognitive approach allows us to better understand which spectators are bvFTD patients and to show interactions between emotions and behavioural disorders.

  9. Frontotemporal dementia caused by CHMP2B mutations

    DEFF Research Database (Denmark)

    Isaacs, A M; Johannsen, P; Holm, I

    2011-01-01

    CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient....... These mutations lead to C-terminal truncations of the CHMP2B protein and we will review recent advances in our understanding of the molecular effects of these mutant truncated proteins on vesicular fusion events within the endosome-lysosome and autophagy degradation pathways. We will also review the clinical...... features of FTD caused by CHMP2B truncation mutations as well as new brain imaging and neuropathological findings. Finally, we collate the current data on CHMP2B missense mutations, which have been reported in FTD and motor neuron disease....

  10. Primary empathy deficits in frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Sandra eBaez

    2014-10-01

    Full Text Available Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD. Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM, social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications.

  11. Primary empathy deficits in frontotemporal dementia

    Science.gov (United States)

    Baez, Sandra; Manes, Facundo; Huepe, David; Torralva, Teresa; Fiorentino, Natalia; Richter, Fabian; Huepe-Artigas, Daniela; Ferrari, Jesica; Montañes, Patricia; Reyes, Pablo; Matallana, Diana; Vigliecca, Nora S.; Decety, Jean; Ibanez, Agustin

    2014-01-01

    Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD). Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral) in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF) or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM), social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications. PMID:25346685

  12. Parkinsonian syndrome in familial frontotemporal dementia.

    Science.gov (United States)

    Siuda, Joanna; Fujioka, Shinsuke; Wszolek, Zbigniew K

    2014-09-01

    Parkinsonism in frontotemporal dementia (FTD) was first described in families with mutations in the microtubule-associated protein tau (MAPT) and progranulin (PRGN) genes. Since then, mutations in several other genes have been identified for FTD with parkinsonism, including chromosome 9 open reading frame 72 (C9ORF72), chromatin modifying protein 2B (CHMP2B), valosin-containing protein (VCP), fused in sarcoma (FUS) and transactive DNA-binding protein (TARDBP). The clinical presentation of patients with familial forms of FTD with parkinsonism is highly variable. The parkinsonism seen in FTD patients is usually characterized by akinetic-rigid syndrome and is mostly associated with the behavioral variant of FTD (bvFTD); however, some cases may present with classical Parkinson's disease. In other cases, atypical parkinsonism resembling progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS) has also been described. Although rare, parkinsonism in FTD may coexist with motor neuron disease. Structural neuroimaging, which is crucial for the diagnosis of FTD, shows characteristic patterns of brain atrophy associated with specific mutations. Structural neuroimaging is not helpful in distinguishing among patients with parkinsonian features. Furthermore, dopaminergic imaging that shows nigrostriatal neurodegeneration in FTD with parkinsonism cannot discriminate parkinsonian syndromes that arise from different mutations. Generally, parkinsonism in FTD is levodopa unresponsive, but there have been cases where a temporary benefit has been reported, so dopaminergic treatment is worth trying, especially, when motor and non-motor manifestations can cause significant problems with daily functioning. In this review, we present an update on the clinical and genetic correlations of FTD with parkinsonism.

  13. Discrete Neural Correlates for the Recognition of Negative Emotions: Insights from Frontotemporal Dementia.

    Directory of Open Access Journals (Sweden)

    Fiona Kumfor

    Full Text Available Patients with frontotemporal dementia have pervasive changes in emotion recognition and social cognition, yet the neural changes underlying these emotion processing deficits remain unclear. The multimodal system model of emotion proposes that basic emotions are dependent on distinct brain regions, which undergo significant pathological changes in frontotemporal dementia. As such, this syndrome may provide important insight into the impact of neural network degeneration upon the innate ability to recognise emotions. This study used voxel-based morphometry to identify discrete neural correlates involved in the recognition of basic emotions (anger, disgust, fear, sadness, surprise and happiness in frontotemporal dementia. Forty frontotemporal dementia patients (18 behavioural-variant, 11 semantic dementia, 11 progressive nonfluent aphasia and 27 healthy controls were tested on two facial emotion recognition tasks: The Ekman 60 and Ekman Caricatures. Although each frontotemporal dementia group showed impaired recognition of negative emotions, distinct associations between emotion-specific task performance and changes in grey matter intensity emerged. Fear recognition was associated with the right amygdala; disgust recognition with the left insula; anger recognition with the left middle and superior temporal gyrus; and sadness recognition with the left subcallosal cingulate, indicating that discrete neural substrates are necessary for emotion recognition in frontotemporal dementia. The erosion of emotion-specific neural networks in neurodegenerative disorders may produce distinct profiles of performance that are relevant to understanding the neurobiological basis of emotion processing.

  14. Discrete Neural Correlates for the Recognition of Negative Emotions: Insights from Frontotemporal Dementia.

    Science.gov (United States)

    Kumfor, Fiona; Irish, Muireann; Hodges, John R; Piguet, Olivier

    2013-01-01

    Patients with frontotemporal dementia have pervasive changes in emotion recognition and social cognition, yet the neural changes underlying these emotion processing deficits remain unclear. The multimodal system model of emotion proposes that basic emotions are dependent on distinct brain regions, which undergo significant pathological changes in frontotemporal dementia. As such, this syndrome may provide important insight into the impact of neural network degeneration upon the innate ability to recognise emotions. This study used voxel-based morphometry to identify discrete neural correlates involved in the recognition of basic emotions (anger, disgust, fear, sadness, surprise and happiness) in frontotemporal dementia. Forty frontotemporal dementia patients (18 behavioural-variant, 11 semantic dementia, 11 progressive nonfluent aphasia) and 27 healthy controls were tested on two facial emotion recognition tasks: The Ekman 60 and Ekman Caricatures. Although each frontotemporal dementia group showed impaired recognition of negative emotions, distinct associations between emotion-specific task performance and changes in grey matter intensity emerged. Fear recognition was associated with the right amygdala; disgust recognition with the left insula; anger recognition with the left middle and superior temporal gyrus; and sadness recognition with the left subcallosal cingulate, indicating that discrete neural substrates are necessary for emotion recognition in frontotemporal dementia. The erosion of emotion-specific neural networks in neurodegenerative disorders may produce distinct profiles of performance that are relevant to understanding the neurobiological basis of emotion processing.

  15. Emotional evaluation and memory in behavioral variant frontotemporal dementia.

    Science.gov (United States)

    St Jacques, Peggy L; Grady, Cheryl; Davidson, Patrick S R; Chow, Tiffany W

    2015-01-01

    Behavioral variant frontotemporal dementia (bvFTD) affects emotional evaluation, but less is known regarding the patients' ability to remember emotional stimuli. Here, bvFTD patients and age-matched controls studied positive, negative, and neutral pictures followed by a recognition memory test. Compared to controls, bvFTD patients showed a reduction in emotional evaluation of negative scenes, but not of positive or neutral scenes. Additionally, the patients showed an overall reduction in recognition memory accuracy, due to impaired recollection in the face of relatively preserved familiarity. These results show that bvFTD reduces the emotional evaluation of negative scenes and impairs overall recognition memory accuracy and recollection.

  16. Italian Frontotemporal Dementia Network (FTD Group-SINDEM): sharing clinical and diagnostic procedures in Frontotemporal Dementia in Italy.

    Science.gov (United States)

    Borroni, B; Turrone, R; Galimberti, D; Nacmias, B; Alberici, A; Benussi, A; Caffarra, P; Caltagirone, C; Cappa, S F; Frisoni, G B; Ghidoni, R; Marra, C; Padovani, A; Rainero, I; Scarpini, E; Silani, V; Sorbi, S; Tagliavini, F; Tremolizzo, L; Bruni, A C

    2015-05-01

    In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers.

  17. Frontotemporal dementia and primary progressive aphasia, a review

    Directory of Open Access Journals (Sweden)

    Kirshner HS

    2014-06-01

    Full Text Available Howard S KirshnerDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USAAbstract: Frontotemporal dementias are neurodegenerative diseases in which symptoms of frontal and/or temporal lobe disease are the first signs of the illness, and as the diseases progress, they resemble a focal left hemisphere process such as stroke or traumatic brain injury, even more than a neurodegenerative disease. Over time, some patients develop a more generalized dementia. Four clinical subtypes characterize the predominant presentations of this illness: behavioral or frontal variant FTD, progressive nonfluent aphasia, semantic dementia, and logopenic primary progressive aphasia. These clinical variants correlate with regional patterns of atrophy on brain imaging studies such as MRI and PET scanning, as well as with biochemical and molecular genetic variants of the disorder. The treatment is as yet only symptomatic, but advances in molecular genetics promise new therapies.Keywords: FTD, behavior variant or frontal variant FTD, pick's disease, PPA, progressive nonfluent aphasia

  18. Behavioral variant of frontotemporal dementia mimicking Huntington's disease

    DEFF Research Database (Denmark)

    Nielsen, T Rune; Bruhn, Peter; Nielsen, Jørgen E

    2010-01-01

    Behavioral changes and cognitive decline are the core clinical manifestations in the behavioral variant of frontotemporal dementia (bv-FTD). The behavioral changes may include characteristic stereotypic movements. These movements, although without clear purpose, are not involuntary. Involuntary m...

  19. Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer's disease.

    Science.gov (United States)

    Zhou, Juan; Greicius, Michael D; Gennatas, Efstathios D; Growdon, Matthew E; Jang, Jung Y; Rabinovici, Gil D; Kramer, Joel H; Weiner, Michael; Miller, Bruce L; Seeley, William W

    2010-05-01

    enhancement within the reciprocal network. In behavioural variant frontotemporal dementia, clinical severity correlated with loss of right frontoinsular Salience Network connectivity and with biparietal Default Mode Network connectivity enhancement. Based on these results, we explored whether a combined index of Salience Network and Default Mode Network connectivity might discriminate between the three groups. Linear discriminant analysis achieved 92% clinical classification accuracy, including 100% separation of behavioural variant frontotemporal dementia and Alzheimer's disease. Patients whose clinical diagnoses were supported by molecular imaging, genetics, or pathology showed 100% separation using this method, including four diagnostically equivocal 'test' patients not used to train the algorithm. Overall, the findings suggest that behavioural variant frontotemporal dementia and Alzheimer's disease lead to divergent network connectivity patterns, consistent with known reciprocal network interactions and the strength and deficit profiles of the two disorders. Further developed, intrinsic connectivity network signatures may provide simple, inexpensive, and non-invasive biomarkers for dementia differential diagnosis and disease monitoring.

  20. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia

    Science.gov (United States)

    Hodges, John R.; Knopman, David; Mendez, Mario F.; Kramer, Joel H.; Neuhaus, John; van Swieten, John C.; Seelaar, Harro; Dopper, Elise G. P.; Onyike, Chiadi U.; Hillis, Argye E.; Josephs, Keith A.; Boeve, Bradley F.; Kertesz, Andrew; Seeley, William W.; Rankin, Katherine P.; Johnson, Julene K.; Gorno-Tempini, Maria-Luisa; Rosen, Howard; Prioleau-Latham, Caroline E.; Lee, Albert; Kipps, Christopher M.; Lillo, Patricia; Piguet, Olivier; Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D.; Fox, Nick C.; Galasko, Douglas; Salmon, David P.; Black, Sandra E.; Mesulam, Marsel; Weintraub, Sandra; Dickerson, Brad C.; Diehl-Schmid, Janine; Pasquier, Florence; Deramecourt, Vincent; Lebert, Florence; Pijnenburg, Yolande; Chow, Tiffany W.; Manes, Facundo; Grafman, Jordan; Cappa, Stefano F.; Freedman, Morris; Grossman, Murray; Miller, Bruce L.

    2011-01-01

    Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised

  1. Paranoid personality masking an atypical case of frontotemporal dementia.

    Science.gov (United States)

    Iroka, Nneka; Jehangir, Waqas; Ii, Jay Littlefield; Pattan, Vishwanath; Yousif, Abdalla; Mishra, Arunesh K

    2015-05-01

    Frontotemporal dementia (FTD) is a debilitating disease that is well described in the "Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5)", and typically presents with memory impairment, progressive decline in cortical functioning, and behavioral changes. Age of onset is generally in the late fifties, and usually the first presentation involves a change in behavior and emotional blunting. Treatment of FTD involves management of any neurobehavioral symptoms while trials of atypical antipsychotics are ongoing but suggest some efficacy. We present a case of a patient who first presented with severe paranoid personality traits and frank persecutory delusions. This atypical presentation of our patient first led to her incorrect diagnosis of a psychotic disorder and paranoid personality disorder. As a result of this diagnosis, she was treated unsuccessfully. A subsequent magnetic resonance imaging (MRI) then showed atrophy of frontal and temporal lobes bilaterally (left more prominent than right) which confirmed the diagnosis of FTD. The importance of this case involves the atypical presentation of paranoia and delusions, and our patient's incorrect diagnosis based on her clinical presentation led to a trial of unsuccessful treatment. Only after performing an MRI, which showed atrophy, was the patient appropriately treated and deemed medically stable. This case report illustrates the importance of considering a rare presentation of frontotemporal lobe dementia with patients who are in the typical age range and present with paranoia and delusions.

  2. Role of Brain Infarcts in Behavioral Variant Frontotemporal Dementia

    Science.gov (United States)

    Torralva, Teresa; Sposato, Luciano A.; Riccio, Patricia M.; Gleichgerrcht, Ezequiel; Roca, María; Toledo, Jon B.; Trojanowski, John Q.; Kukull, Walter A.; Manes, Facundo; Hachinski, Vladimir

    2015-01-01

    Diagnosing behavioral variant frontotemporal dementia (bvFTD) in patients with prior history of stroke or with silent brain infarcts on neuroimaging studies can be challenging. Vascular changes in patients with bvFTD are not unusual, but bvFTD tends to be ruled out in the presence of cerebrovascular disease. We aimed to identify the clinical, cognitive, and risk factor profile of bvFTD with coexistent cerebrovascular disease (V-bvFTD). We compared demographic data, clinical diagnoses, vascular risk factors, functional status, and normalized neuropsychological z-scores between patients with V-bvFTD vs. bvFTD without concomitant cerebrovascular disease (NV-bvFTD) from the National Alzheimer’s Coordinating Centre database. We included 391 neuropathologically diagnosed cases of frontotemporal lobe degeneration (FTLD). We excluded patients that were diagnosed with aphasic variants of frontotemporal dementia before death. Patients with V-bvFTD (n=62) were older at the time of onset of cognitive decline (71.6 vs. 62.5years, p<0.001) and death (78.7 vs. 69.6, p<0.001), more likely to be hypertensive (75.8 vs. 45.7%, p=0.002), and to have a history of stroke (21.2 vs. 6.1%, p=0.007) than those with NV-bvFTD (n=329). V-bvFTD was often underdiagnosed, affected elderly patients, and had a similar cognitive profile as NV-bvFTD despite the presence of brain infarcts. In the whole cohort, we observed enhanced cognitive performance with increasing age quintiles despite larger proportions of cerebrovascular disease pathology, likely meaning that FTLD-related primary neurodegeneration exerts a stronger impact on cognition than cerebrovascular disease. Coexisting cerebrovascular disease should not preclude the diagnosis of bvFTD. PMID:26220367

  3. Quantitative electroencephalography in frontotemporal dementia with methylphenidate response: a case study.

    Science.gov (United States)

    Goforth, Harold W; Konopka, Lukasz; Primeau, Margaret; Ruth, Amity; O'Donnell, Kathleen; Patel, Roopal; Poprawski, Teresa; Shirazi, Parvez; Rao, Murali

    2004-04-01

    Frontotemporal dementia is an underdiagnosed illness with predominant behavioral and executive manifestations. Historically, diagnosis has been based on a combination of clinical history, neuropsychological testing, and brain imaging. No effective treatment currently exists for this disorder. A case is presented using quantitative EEG with methylphenidate challenge correlated with SPECT. The patient underwent neuropsychological testing, a SPECT brain study, and a quantitative EEG, which was repeated after methylphenidate administration. SPECT was significant for hypoperfusion to the bilateral frontotemporal regions, with left-sided hypoperfusion greater than homologous right as demonstrated by LORETA analysis. QEEG correlated with SPECT, and demonstrated profound left greater than right bi-frontotemporal slowing, which normalized partially after methylphenidate administration. The patient has remained on methylphenidate as an outpatient, and has had significant behavioral improvement. Quantitative EEG may provide both diagnostic and therapeutic data with regard to frontotemporal dementia. Further studies of methylphenidate in this population are needed to confirm these data.

  4. Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

    Science.gov (United States)

    ... myopathy with early-onset Paget disease and frontotemporal dementia Enable Javascript to view the expand/collapse boxes. ... myopathy with early-onset Paget disease and frontotemporal dementia ( IBMPFD ) is a condition that can affect the ...

  5. Oxytocin for frontotemporal dementia: a systematic review.

    Science.gov (United States)

    Tampi, Rajesh R; Maksimowski, Michael; Ahmed, Mohsina; Tampi, Deena J

    2017-01-01

    The aim of this systematic review is to identify published randomized controlled trials (RCTs) that evaluated the use of oxytocin in individuals with frontotemporal dementia (FTD). A literature search was conducted of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases for RCTs in any language that evaluated the use of oxytocin in individuals with FTD. Bibliographic databases of published articles were also searched for additional studies. A total of two RCTs that evaluated the use of oxytocin in individuals with FTD were identified. In one study, the use of oxytocin in individuals with FTD produced a reduction in identification of negative facial expressions (anger and fear) which can be hypothesized to improve trust and increase cooperation in these individuals. Both studies noted oxytocin was well tolerated and showed short term benefits on behavioral symptoms in individuals with FTD. Oxytocin appears to improve social aspects of cognition and behavioral symptoms in individuals with FTD and is well tolerated. However, positive data from larger and longer duration RCTs are needed before the routine use of oxytocin in individuals with FTD can be recommended.

  6. Therapeutic and diagnostic challenges for frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Simon eD'Alton

    2014-08-01

    Full Text Available In the search for therapeutic modifiers, frontotemporal dementia (FTD has traditionally been overshadowed by other conditions such as Alzheimer’s disease. A clinically and pathologically diverse condition, FTD has been galvanized by a number of recent discoveries such as novel genetic variants in familial and sporadic forms of disease and the identification of TAR DNA binding protein of 43kDa (TDP-43 as the defining constituent of inclusions in more than half of cases. In combination with an ever-expanding knowledge of the function and dysfunction of tau - a protein which is pathologically aggregated in the majority of the remaining cases - there exists a greater understanding of FTD than ever before. These advances may indicate potential approaches for the development of hypothetical therapeutics, but FTD remains highly complex and the roles of tau and TDP-43 in neurodegeneration are still wholly unclear. Here the challenges facing potential therapeutic strategies are discussed, which include sufficiently accurate disease diagnosis and sophisticated technology to deliver effective therapies.

  7. The impact of dementia severity on caregiver burden in frontotemporal dementia and Alzheimer disease.

    Science.gov (United States)

    Mioshi, Eneida; Foxe, David; Leslie, Felicity; Savage, Sharon; Hsieh, Sharpley; Miller, Laurie; Hodges, John R; Piguet, Olivier

    2013-01-01

    Caregiver burden is greater in frontotemporal dementia (FTD) than in Alzheimer disease (AD). However, little is known of the impact of the 3 main clinical variants of FTD- behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SemDem), and progressive nonfluent aphasia (PNFA)-or the role of disease severity in caregiver burden. The Zarit Burden Inventory was used to measure caregiver burden of bvFTD (n=17), SemDem (n=20), PNFA (n=20), and AD (n=19) patients. Symptom duration, caregiver age, and relationship type were matched across groups. Moreover, a number of caregiver (mood, social network) and patient variables (functional disability, behavioral changes, relationship with caregiver, and dementia stage) were addressed to investigate their impact on caregiver burden. Caregivers of bvFTD patients reported the highest burden, whereas SemDem and PNFA caregivers reported burden similar to AD. A regression analysis revealed that caregiver burden in FTD, regardless of subtype, was explained by a model combining disease staging, relationship changes, and caregiver depression. Burden increased with disease severity in FTD. This study is the first to show that caregivers of SemDem, PNFA, and AD patients show similar burden, while confirming that bvFTD caregivers show higher burden than AD caregivers. More importantly, this study demonstrates that burden worsens with disease progression in FTD.

  8. Frontotemporal dementia selectively impairs transitive reasoning about familiar spatial environments.

    Science.gov (United States)

    Vartanian, Oshin; Goel, Vinod; Tierney, Michael; Huey, Edward D; Grafman, Jordan

    2009-09-01

    Although patients with frontotemporal dementia (FTD) are known to exhibit a wide range of cognitive and personality difficulties, some evidence suggests that there may be a degree of selectivity in their reasoning impairments. Based on a recent review of the neuroimaging literature on reasoning, the authors hypothesized that the presence or absence of familiar content may have a selective impact on the reasoning abilities of patients with FTD. Specifically, the authors predicted that patients with frontal-variant FTD would be more impaired when reasoning about transitive arguments involving familiar spatial environments than when reasoning about identical logical arguments involving unfamiliar spatial environments. As predicted, patients with FTD were less accurate than normal controls only when the content of arguments involved familiar spatial environments. These results indicate a degree of selectivity in the cognitive deficits of this patient population and suggest that the frontal-temporal lobe system may play a necessary role in reasoning about familiar material.

  9. A study of cortical excitability, central motor conduction, and cortical inhibition using single pulse transcranial magnetic stimulation in patients with early frontotemporal and Alzheimer′s dementia

    Directory of Open Access Journals (Sweden)

    Sadanandavalli Retnaswami Chandra

    2016-01-01

    Full Text Available Introduction: Degenerative cortical dementias affect several million people worldwide. Early diagnosis and categorization are essential for initiating appropriate pharmacological and nonpharmacological treatment so that deterioration can be postponed, and disability adjusted life years can be saved both for the patient and for the caregiver. Therefore, an early, simple, noninvasive biomarker will serve as a boon. Patients and Methods: Patients who satisfied probable Alzheimer′s disease (AD or frontotemporal dementia (FTD using international consensus criteria for FTD and National Institute of Neurological Disorders and Stroke-AD and Related Disorders Association criteria for AD were evaluated using single pulse transcranial magnetic stimulation with figure of eight coil and motor evoked potential from right first dorsal interossei. Resting threshold (MT, central motor conduction time (CMCT, and silent period (SP were evaluated. Results: Resting MT and SP are reduced in patients with Alzheimer′s disease whereas CMCT is prolonged in patients with FTD and SP is in the lower limit of normal in both conditions. Conclusion: The patterns of central motor conduction and MT are distinctly different in patients with early Alzheimer′s disease (AD and FTD.

  10. Clinical and Neuropsychological Characteristics of a Nationwide Hospital-Based Registry of Frontotemporal Dementia Patients in Korea: A CREDOS-FTD Study

    Directory of Open Access Journals (Sweden)

    Eun-Joo Kim

    2014-07-01

    Full Text Available Background: We investigated the demographic, clinical, and neuropsychological characteristics of frontotemporal dementia (FTD from the Clinical Research Center for Dementia of South Korea (CREDOS-FTD registry. Methods: A total of 200 consecutive patients with FTD recruited from 16 neurological clinics in Korea were evaluated by cognitive and functional assessments, a screening test for aphasia, behavioral questionnaires, motor assessments, and brain MRI or PET. Results: In our registry, 78 patients were classified as having been diagnosed with behavioral-variant FTD (bvFTD, 70 with semantic dementia (SD, 33 with progressive nonfluent aphasia (PNFA, and 8 with motor neuron disease plus syndrome (MND-plus. The patients with language variants of dementia were older than those with bvFTD. There were no differences in sex ratio, duration of illness, or level of education among the four subgroups. Overall, the patients with bvFTD showed a significantly better performance in cognitive tests. A higher frequency of motor symptoms and a lower frequency of behavioral symptoms were found in PNFA than in bvFTD and SD. The Global Language Index was significantly lower in SD than in bvFTD and PNFA. The MND-plus group had a poorer performance than all the others in all cognitive domains. Conclusion: The neuropsychological, behavioral, motor, and language characteristics of the four subtypes are comparable with those from other series. However, the proportion of SD (37.0%, which was similar to that of bvFTD (41.3%, was higher in our registry than in other series.

  11. The unique predisposition to criminal violations in frontotemporal dementia.

    Science.gov (United States)

    Mendez, Mario F

    2010-01-01

    Brain disorders can lead to criminal violations. Patients with frontotemporal dementia (FTD) are particularly prone to sociopathic behavior while retaining knowledge of their acts and of moral and conventional rules. This report describes four FTD patients who committed criminal violations in the presence of clear consciousness and sufficiently intact cognition. They understood the nature of their acts and the potential consequences, but did not feel sufficiently concerned to be deterred. FTD involves a unique pathologic combination affecting the ventromedial prefrontal cortex, with altered moral feelings, right anterior temporal loss of emotional empathy, and orbitofrontal changes with disinhibited, compulsive behavior. These case histories and the literature indicate that those with right temporal FTD retain the capacity to tell right from wrong but have the slow and insidious loss of the capacity for moral rationality. Patients with early FTD present a challenge to the criminal justice system to consider alterations in moral cognition before ascribing criminal responsibility.

  12. MRI patterns of atrophy and hypoperfusion associations across brain regions in frontotemporal dementia.

    Science.gov (United States)

    Tosun, Duygu; Rosen, Howard; Miller, Bruce L; Weiner, Michael W; Schuff, Norbert

    2012-02-01

    Magnetic Resonance Imaging (MRI) provides various imaging modes to study the brain. We tested the benefits of a joint analysis of multimodality MRI data in combination with a large-scale analysis that involved simultaneously all image voxels using joint independent components analysis (jICA) and compared the outcome to results using conventional voxel-by-voxel unimodality tests. Specifically, we designed a jICA to decompose multimodality MRI data into independent components that explain joint variations between the image modalities as well as variations across brain regions. We tested the jICA design on structural and perfusion-weighted MRI data from 12 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and 12 cognitively normal elderly individuals. While unimodality analyses showed widespread brain atrophy and hypoperfusion in the patients, jICA further revealed two significant joint components of variations between atrophy and hypoperfusion across brain regions. The 1st joint component revealed associated brain atrophy and hypoperfusion predominantly in the right brain hemisphere in behavioral variant frontotemporal dementia, and the 2nd joint component revealed greater atrophy relative to hypoperfusion affecting predominantly the left hemisphere in behavioral variant frontotemporal dementia. The patterns are consistent with the clinical symptoms of behavioral variant frontotemporal dementia that relate to asymmetric compromises of the left and right brain hemispheres. The joint components also revealed that that structural alterations can be associated with physiological alterations in spatially separated but potentially connected brain regions. Finally, jICA outperformed voxel-by-voxel unimodal tests significantly in terms of an effect size, separating the behavioral variant frontotemporal dementia patients from the controls. Taken together, the results demonstrate the benefit of multimodality MRI in conjunction with jICA for mapping

  13. A Study of Cortical Excitability, Central Motor Conduction, and Cortical Inhibition Using Single Pulse Transcranial Magnetic Stimulation in Patients with Early Frontotemporal and Alzheimer's Dementia.

    Science.gov (United States)

    Chandra, Sadanandavalli Retnaswami; Issac, Thomas Gregor; Nagaraju, B C; Philip, Mariamma

    2016-01-01

    Degenerative cortical dementias affect several million people worldwide. Early diagnosis and categorization are essential for initiating appropriate pharmacological and nonpharmacological treatment so that deterioration can be postponed, and disability adjusted life years can be saved both for the patient and for the caregiver. Therefore, an early, simple, noninvasive biomarker will serve as a boon. Patients who satisfied probable Alzheimer's disease (AD) or frontotemporal dementia (FTD) using international consensus criteria for FTD and National Institute of Neurological Disorders and Stroke-AD and Related Disorders Association criteria for AD were evaluated using single pulse transcranial magnetic stimulation with figure of eight coil and motor evoked potential from right first dorsal interossei. Resting threshold (MT), central motor conduction time (CMCT), and silent period (SP) were evaluated. Resting MT and SP are reduced in patients with Alzheimer's disease whereas CMCT is prolonged in patients with FTD and SP is in the lower limit of normal in both conditions. The patterns of central motor conduction and MT are distinctly different in patients with early Alzheimer's disease (AD) and FTD.

  14. Induced pluripotent stem cells (iPSCs) derived from a patient with frontotemporal dementia caused by a R406W mutation in microtubule-associated protein tau (MAPT)

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena E.; Hasholt, Lis F.

    2016-01-01

    Skin fibroblasts were obtained from a 59-year-old woman diagnosed with frontotemporal dementia. The disease is caused by a R406W mutation in microtubule-associated protein tau (MAPT). Induced pluripotent stem cells (iPSCs) were established by electroporation with episomal plasmids containing hOCT4...

  15. Induced pluripotent stem cells (iPSCs) derived from a patient with frontotemporal dementia caused by a P301L mutation in microtubule-associated protein tau (MAPT)

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena Elisabeth; Hasholt, Lis Frydenreich

    2016-01-01

    Skin fibroblasts were obtained froma 57-year-old woman diagnosed with frontotemporal dementia. The diseaseis caused by a P301L mutation in microtubule-associated protein tau (MAPT). Induced pluripotent stem cells (iPSCs) were established by electroporation with episomal plasmids containing hOCT4, h...

  16. Loss of TBK1 is a frequent cause of frontotemporal dementia in a Belgian cohort

    NARCIS (Netherlands)

    Gijselinck, Ilse; Van Mossevelde, Sara; van der Zee, Julie; Sieben, Anne; Philtjens, Stephanie; Heeman, Bavo; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; De Baets, Greet; Baumer, Veerle; Cuijt, Ivy; Van den Broeck, Marleen; Peeters, Karin; Mattheijssens, Maria; Rousseau, Frederic; Vandenberghe, Rik; De Jonghe, Peter; Cras, Patrick; De Deyn, Peter P.; Martin, Jean-Jacques; Cruts, Marc; Van Broeckhoven, Christine

    2015-01-01

    Objective:To assess the genetic contribution of TBK1, a gene implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and FTD-ALS, in Belgian FTD and ALS patient cohorts containing a significant part of genetically unresolved patients.Methods:We sequenced TBK1 in a

  17. A Scale of Socioemotional Dysfunction in Frontotemporal Dementia

    Science.gov (United States)

    Barsuglia, Joseph P.; Kaiser, Natalie C.; Wilkins, Stacy Schantz; Joshi, Aditi; Barrows, Robin J.; Paholpak, Pongsatorn; Panchal, Hemali Vijay; Jimenez, Elvira E.; Mather, Michelle J.; Mendez, Mario F.

    2014-01-01

    Early social dysfunction is a hallmark symptom of behavioral variant frontotemporal dementia (bvFTD); however, validated measures for assessing social deficits in dementia are needed. The purpose of the current study was to examine the utility of a novel informant-based measure of social impairment, the Socioemotional Dysfunction Scale (SDS) in early-onset dementia. Sixteen bvFTD and 18 early-onset Alzheimer’s disease (EOAD) participants received standard clinical neuropsychological measures and neuroimaging. Caregiver informants were administered the SDS. Individuals with bvFTD exhibited greater social dysfunction on the SDS compared with the EOAD group; t(32) = 6.32, p < .001. The scale demonstrated preliminary evidence for discriminating these frequently misdiagnosed groups (area under the curve = 0.920, p = <.001) and internal consistency α = 0.977. The SDS demonstrated initial evidence as an effective measure for detecting abnormal social behavior and discriminating bvFTD from EOAD. Future validation is recommended in larger and more diverse patient groups. PMID:25331776

  18. My belief or yours? Differential theory of mind deficits in frontotemporal dementia and Alzheimer's disease.

    Science.gov (United States)

    Le Bouc, Raphaël; Lenfant, Pierre; Delbeuck, Xavier; Ravasi, Laura; Lebert, Florence; Semah, Franck; Pasquier, Florence

    2012-10-01

    Theory of mind reasoning-the ability to understand someone else's mental states, such as beliefs, intentions and desires-is crucial in social interaction. It has been suggested that a theory of mind deficit may account for some of the abnormalities in interpersonal behaviour that characterize patients affected by behavioural variant frontotemporal dementia. However, there are conflicting reports as to whether understanding someone else's mind is a key difference between behavioural variant frontotemporal dementia and other neurodegenerative conditions such as Alzheimer's disease. Literature data on the relationship between theory of mind abilities and executive functions are also contradictory. These disparities may be due to underestimation of the fractionation within theory of mind components. A recent theoretical framework suggests that taking someone else's mental perspective requires two distinct processes: inferring someone else's belief and inhibiting one's own belief, with involvement of the temporoparietal and right frontal cortices, respectively. Therefore, we performed a neuropsychological and neuroimaging study to investigate the hypothesis whereby distinct cognitive deficits could impair theory of mind reasoning in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia. We used a three-option false belief task to assess theory of mind components in 11 patients with behavioural variant frontotemporal dementia, 12 patients with Alzheimer's disease and 20 healthy elderly control subjects. The patients with behavioural variant frontotemporal dementia and those with Alzheimer's disease were matched for age, gender, education and global cognitive impairment. [(18)F]-fluorodeoxyglucose-positron emission tomography imaging was used to investigate neural correlates of theory of mind reasoning deficits. Performance in the three-option false belief task revealed differential impairments in the components of theory of mind

  19. Randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes

    OpenAIRE

    Justin B. Miller; Banks, Sarah J.; Léger, Gabriel C; Cummings, Jeffrey L.

    2014-01-01

    Progress has been made in understanding the genetics and molecular biology of frontotemporal dementia (FTD). Targets for intervention have been identified, therapies are being developed, and clinical trials are advancing. A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous phenotypes. The neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction, language impairments and behavioral disturb...

  20. Distinct perfusion patterns in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies

    Energy Technology Data Exchange (ETDEWEB)

    Binnewijzend, Maja A.A.; Wattjes, Mike P.; Berckel, Bart N.M. van; Barkhof, Frederik [VU University Medical Center and Neuroscience Campus Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Kuijer, Joost P.A. [VU University Medical Center and Neuroscience Campus Amsterdam, Department of Physics and Medical Technology, Amsterdam (Netherlands); Flier, Wiesje M. van der [VU University Medical Center and Neuroscience Campus Amsterdam, Alzheimercenter and Department of Neurology, Amsterdam (Netherlands); VU University Medical Center and Neuroscience Campus Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Benedictus, Marije R.; Moeller, Christiane M.; Pijnenburg, Yolande A.L.; Lemstra, Afina W.; Prins, Niels D.; Scheltens, Philip [VU University Medical Center and Neuroscience Campus Amsterdam, Alzheimercenter and Department of Neurology, Amsterdam (Netherlands)

    2014-09-15

    To compare pseudo-continuous arterial spin-labelled (PCASL) magnetic resonance imaging (MRI) measured quantitative cerebral blood flow (CBF) of patients with frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), Alzheimer's disease (AD) and controls, in a region of interest (ROI) and voxel-wise fashion. We analysed whole-brain 3D fast-spin-echo PCASL images of 20 FTD patients, 14 DLB patients, 48 AD patients and 50 controls from the Amsterdam Dementia Cohort. Regional CBF patterns were compared using analyses of variance for repeated measures. Permutation tests were used for voxel-wise comparisons. Analyses were performed using uncorrected and partial volume corrected (PVC) maps. All analyses were corrected for age and sex. There was an interaction between diagnosis and region (p < 0.001), implying differences in regional CBF changes between diagnostic groups. In AD patients, CBF was decreased in all supratentorial regions, most prominently so in the posterior regions. DLB patients showed lowest CBF values throughout the brain, but temporal CBF was preserved. Supratentorial PVC cortical CBF values were lowest in the frontal lobes in FTD patients, and in the temporal lobes in AD patients. Patients with AD, FTD and DLB display distinct patterns of quantitative regional CBF changes. 3D-PCASL may provide additional value in the workup of dementia patients. (orig.)

  1. Apathy in Frontotemporal Dementia: Behavioral and Neuroimaging Correlates

    Directory of Open Access Journals (Sweden)

    Paul J. Eslinger

    2012-01-01

    Full Text Available We investigated the occurrence of goal-directed motivational change in the form of apathy in patients with frontotemporal dementia (FTD, particularly those with behavioral variant social and executive deficits (bvFTD. Standardized behavioral inventory was employed to survey and compare apathy ratings from patients and caregivers. In cases of bvFTD, apathy ratings were further related to measures of social cognition, executive function, and atrophy on brain MRI. Results indicated that caregivers rated bvFTD patients as having significantly elevated apathy scores though patient self-ratings were normal. Caregiver and self-ratings of FTD samples with progressive nonfluent aphasia and semantic dementia did not differ from healthy controls and their informants. In the bvFTD sample, caregiver apathy scores were not correlated with general cognitive screening or depression scores, but were significantly correlated with social cognition and executive function measures. Voxel-based morphometry revealed that apathy ratings in bvFTD were related to prominent atrophy in the right caudate (including the ventral striatum, the right temporo-parietal junction, right posterior inferior and middle temporal gyri, and left frontal operculum- anterior insula region. Findings suggest that bvFTD is associated with a significant breakdown in goal-directed motivated behavior involving disruption of cortical-basal ganglia circuits that is also related to social and executive function deficits.

  2. Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations

    DEFF Research Database (Denmark)

    Urwin, Hazel; Authier, Astrid; Nielsen, Jørgen Erik

    2010-01-01

    Mutations in CHMP2B cause frontotemporal dementia (FTD) in a large Danish pedigree, which is termed FTD linked to chromosome 3 (FTD-3), and also in an unrelated familial FTD patient. CHMP2B is a component of the ESCRT-III complex, which is required for function of the multivesicular body (MVB), a...

  3. Efficacy of Electroconvulsive Therapy for Comorbid Frontotemporal Dementia with Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Sean Paul

    2013-01-01

    Full Text Available Challenges encountered in the diagnosis and treatment of frontotemporal dementia (FTD are further confounded when presented with comorbid psychiatric disorder. Here we report a case of progressive FTD in a patient with a long history of bipolar affective disorder (BAD 1, depressed type. We also report beneficial effects of electroconvulsive therapy and its potential application in similar comorbid disorders.

  4. Animal Models for Alzheimer's Disease and Frontotemporal Dementia: A Perspective

    Directory of Open Access Journals (Sweden)

    Jürgen Götz

    2009-10-01

    Full Text Available In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as diverse as mice, fish, flies and worms. Advances in imaging and therapy are explored. We also discuss some anticipated new models and developments. These will reveal how key players in the pathogenesis of Alzheimer's disease and frontotemporal dementia, such as the peptide Aβ (amyloid β and the protein tau, cause neuronal dysfunction and eventually, neuronal demise. Understanding these processes fully will lead to early diagnosis and therapy.

  5. Animal models for Alzheimer's disease and frontotemporal dementia: a perspective

    Directory of Open Access Journals (Sweden)

    Jürgen Götz

    2009-11-01

    Full Text Available In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as diverse as mice, fish, flies and worms. Advances in imaging and therapy are explored. We also discuss some anticipated new models and developments. These will reveal how key players in the pathogenesis of Alzheimer's disease and frontotemporal dementia, such as the peptide Aβ (amyloid β and the protein tau, cause neuronal dysfunction and eventually, neuronal demise. Understanding these processes fully will lead to early diagnosis and therapy.

  6. Induced pluripotent stem cells (iPSCs) derived from a patient with frontotemporal dementia caused by a P301L mutation in microtubule-associated protein tau (MAPT)

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena Elisabeth; Hasholt, Lis Frydenreich;

    2016-01-01

    Skin fibroblasts were obtained froma 57-year-old woman diagnosed with frontotemporal dementia. The diseaseis caused by a P301L mutation in microtubule-associated protein tau (MAPT). Induced pluripotent stem cells (iPSCs) were established by electroporation with episomal plasmids containing hOCT4, h......SOX2, hKLF2, hL-MYC,hLIN-28 and shP53. iPSCs were free of genomically integrated reprogramming genes, contained the expected c.902C>T substitution in exon 10 of the MAPT gene, expressed the expected pluripotency markers, displayed in vitro differentiation potential to the three germ layers and had...... normal karyotype. The iPSC line may be useful for studying hereditary frontotemporal dementia and TAU pathology in vitro....

  7. Profiling of Ubiquitination Pathway Genes in Peripheral Cells from Patients with Frontotemporal Dementia due to C9ORF72 and GRN Mutations

    Directory of Open Access Journals (Sweden)

    Maria Serpente

    2015-01-01

    Full Text Available We analysed the expression levels of 84 key genes involved in the regulated degradation of cellular protein by the ubiquitin-proteasome system in peripheral cells from patients with frontotemporal dementia (FTD due to C9ORF72 and GRN mutations, as compared with sporadic FTD and age-matched controls. A SABiosciences PCR array was used to investigate the transcription profile in a discovery population consisting of six patients each in C9ORF72, GRN, sporadic FTD and age-matched control groups. A generalized down-regulation of gene expression compared with controls was observed in C9ORF72 expansion carriers and sporadic FTD patients. In particular, in both groups, four genes, UBE2I, UBE2Q1, UBE2E1 and UBE2N, were down-regulated at a statistically significant (p < 0.05 level. All of them encode for members of the E2 ubiquitin-conjugating enzyme family. In GRN mutation carriers, no statistically significant deregulation of ubiquitination pathway genes was observed, except for the UBE2Z gene, which displays E2 ubiquitin conjugating enzyme activity, and was found to be statistically significant up-regulated (p = 0.006. These preliminary results suggest that the proteasomal degradation pathway plays a role in the pathogenesis of FTD associated with TDP-43 pathology, although different proteins are altered in carriers of GRN mutations as compared with carriers of the C9ORF72 expansion.

  8. Demencia frontotemporal no familiar y epilepsia generalizada Frontotemporal dementia non familial and generalized epilepsy

    Directory of Open Access Journals (Sweden)

    Patricio Fuentes

    2005-12-01

    Full Text Available Se presenta un paciente de 62 años, sin antecedentes familiares de demencia, que a los 45 años debuta con crisis súbitas de disnea, visión borrosa, caída al suelo y movimientos repetitivos de brazos. Tratado por epilepsia con fenitoína y ácido valproico, repite esporádicamente crisis semejantes. Hace 4 años sus familiares notan cambios de personalidad, irritabilidad y conductas obsesivas. Hace 2 años aparecen episodios de desorientación de días de duración, algunos con alucinaciones auditivas y también fenómenos convulsivos. Ultimamente presenta crisis polimorfas, algunas con prolongada alteración de conciencia, estados catatoniformes y relajación esfinteriana. Examen físico y neurológico sin anormalidades. Evaluación neuropsicológica evidenció consistentes defectos en funciones frontales. EEG mostraron lentitud generalizada y actividad irritativa esporádica en regiones frontotemporales. Atrofia cortical de predominio anterior en CT scan e hipoperfusión fronto-temporal bilateral en SPECT. Exámenes de laboratorio y LCR normales. CONCLUSIÓN: La asociación de DFT con epilepsia, en forma no familiar, sugiere un síndrome neurodegenerativo cortical diferente.A 62 year-old patient is presented, without family antecedents of dementia who begins with 45 years of age with sudden crisis of dyspnea, blurred vision, fall to the floor and repetitive jerks of arms. Tried by epilepsy with phenytoin and valproate repeats similar crisis sporadically. Four years ago their relatives began to notice changes of personality, irritability and obsessive behaviors. Later on, are added episodes of disorientation of days of duration, some with auditory hallucinations and also convulsive manifestations. Finally appear polymorphic crisis, some with continue alteration of consciousness, catatonic states and sphincteric incontinence. Physical and neurological examination without abnormalities. Neuropsychological evaluation evidenced consistent

  9. Genetic analysis of frontotemporal dementia and progressive supra nuclear palsy

    OpenAIRE

    Ferrari, R.

    2014-01-01

    Genome-wide association study (GWAS) is an effective method for mapping genetic variants underlying common and complex diseases. This thesis describes the investigation of the disorders, frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). FTD affects the frontal/temporal lobes and presents behavioural changes (bvFTD), cognitive decline or language dysfunction (primary progressive aphasia [PPA]), whilst PSP affects predominantly the brain stem resulting in loss of balance, ...

  10. Neurofilament light chain: a biomarker for genetic frontotemporal dementia.

    Science.gov (United States)

    Meeter, Lieke H; Dopper, Elise G; Jiskoot, Lize C; Sanchez-Valle, Raquel; Graff, Caroline; Benussi, Luisa; Ghidoni, Roberta; Pijnenburg, Yolande A; Borroni, Barbara; Galimberti, Daniela; Laforce, Robert Jr; Masellis, Mario; Vandenberghe, Rik; Ber, Isabelle Le; Otto, Markus; van Minkelen, Rick; Papma, Janne M; Rombouts, Serge A; Balasa, Mircea; Öijerstedt, Linn; Jelic, Vesna; Dick, Katrina M; Cash, David M; Harding, Sophie R; Jorge Cardoso, M; Ourselin, Sebastien; Rossor, Martin N; Padovani, Alessandro; Scarpini, Elio; Fenoglio, Chiara; Tartaglia, Maria C; Lamari, Foudil; Barro, Christian; Kuhle, Jens; Rohrer, Jonathan D; Teunissen, Charlotte E; van Swieten, John C

    2016-08-01

    To evaluate cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL) levels in genetic frontotemporal dementia (FTD) as a potential biomarker in the presymptomatic stage and during the conversion into the symptomatic stage. Additionally, to correlate NfL levels to clinical and neuroimaging parameters. In this multicenter case-control study, we investigated CSF NfL in 174 subjects (48 controls, 40 presymptomatic carriers and 86 patients with microtubule-associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72) mutations), and serum NfL in 118 subjects (39 controls, 44 presymptomatic carriers, 35 patients). In 55 subjects both CSF and serum was determined. In two subjects CSF was available before and after symptom onset (converters). Additionally, NfL levels were correlated with clinical parameters, survival, and regional brain atrophy. CSF NfL levels in patients (median 6762 pg/mL, interquartile range 3186-9309 pg/mL) were strongly elevated compared with presymptomatic carriers (804 pg/mL, 627-1173 pg/mL, P NfL correlated highly with CSF NfL (r s = 0.87, P NfL after disease onset. Additionally, NfL levels in patients correlated with disease severity, brain atrophy, annualized brain atrophy rate and survival. NfL in both serum and CSF has the potential to serve as a biomarker for clinical disease onset and has a prognostic value in genetic FTD.

  11. Precision medicine of frontotemporal dementia: from genotype to phenotype.

    Science.gov (United States)

    Che, Xiang-Qian; Song, Ning; Gao, Ying; Ren, Ru-Jing; Wang, Gang

    2018-01-01

    Frontotemporal dementia (FTD) is the second most common neurodegenerative  cause of early-onset dementia. FTD has an important genetic component contributing to its pathogenic mechanisms. Currently, extensive research on neuroimaging biomarkers and neurochemical biomarkers in FTD is being conducted to address the clinical need for a sensitive and specific diagnostic marker. Here, we review the advances in genetics, biomarkers and treatment of FTD and how this may represent a shift towards precision medicine. To advance the clinical use of precision medicine, big data cohort for genotype/phenotype research and multidisciplinary team approaches are necessary.

  12. Validation of a prefractionation method followed by two-dimensional electrophoresis – Applied to cerebrospinal fluid proteins from frontotemporal dementia patients

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    Sjögren Magnus

    2004-11-01

    Full Text Available Abstract Background The aim of this study was firstly, to improve and validate a cerebrospinal fluid (CSF prefractionation method followed by two-dimensional electrophoresis (2-DE and secondly, using this strategy to investigate differences between the CSF proteome of frontotemporal dementia (FTD patients and controls. From each subject three ml of CSF was prefractionated using liquid phase isoelectric focusing prior to 2-DE. Results With respect to protein recovery and purification potential, ethanol precipitation of the prefractionated CSF sample was found superior, after testing several sample preparation methods. The reproducibility of prefractionated CSF analyzed on 2-D gels was comparable to direct 2-DE analysis of CSF. The protein spots on the prefractionated 2-D gels had an increased intensity, indicating a higher protein concentration, compared to direct 2-D gels. Prefractionated 2-DE analysis of FTD and control CSF showed that 26 protein spots were changed at least two fold. Using mass spectrometry, 13 of these protein spots were identified, including retinol-binding protein, Zn-α-2-glycoprotein, proapolipoproteinA1, β-2-microglobulin, transthyretin, albumin and alloalbumin. Conclusion The results suggest that the prefractionated 2-DE method can be useful for enrichment of CSF proteins and may provide a new tool to investigate the pathology of neurodegenerative diseases. This study confirmed reduced levels of retinol-binding protein and revealed some new biomarker candidates for FTD.

  13. Parkinsonism, movement disorders and genetics in frontotemporal dementia.

    Science.gov (United States)

    Baizabal-Carvallo, José Fidel; Jankovic, Joseph

    2016-03-01

    Frontotemporal dementia (FTD) refers to a group of clinically and genetically heterogeneous neurodegenerative disorders that are a common cause of adult-onset behavioural and cognitive impairment. FTD often presents in combination with various hyperkinetic or hypokinetic movement disorders, and evidence suggests that various genetic mutations underlie these different presentations. Here, we review the known syndromatic-genetic correlations in FTD. Although no direct genotype-phenotype correlations have been identified, mutations in multiple genes have been associated with various presentations. Mutations in the genes that encode microtubule-associated protein tau (MAPT) and progranulin (PGRN) can manifest as symmetrical parkinsonism, including the phenotypes of Richardson syndrome and corticobasal syndrome (CBS). Expansions in the C9orf72 gene are most frequently associated with familial FTD, typically combined with motor neuron disease, but other manifestations, such as symmetrical parkinsonism, CBS and multiple system atrophy-like presentations, have been described in patients with these mutations. Less common gene mutations, such as those in TARDBP, CHMP2B, VCP, FUS and TREM2, can also present as atypical parkinsonism. The most common hyperkinetic movement disorders in FTD are motor and vocal stereotypies, which have been observed in up to 78% of patients with autopsy-proven FTD. Other hyperkinetic movements, such as chorea, orofacial dyskinesias, myoclonus and dystonia, are also observed in some patients with FTD.

  14. Frontotemporal dementia: clinical, neuropscyhological, and neuroimaging description

    Directory of Open Access Journals (Sweden)

    Juan Carlos Rivas Nieto

    2014-11-01

    Full Text Available Objetivo: Describir la relación entre los hallazgos clínicos, neuropsicológicos e imagenológicos en un grupo de pacientes con el diagnóstico de DFT. Métodos: Se revisaron las historias clínicas, pruebas cognitivas e imágenes cerebrales estructurales y de perfusión de 21 pacientes del Hospital Psiquiátrico Universitario del Valle, Cali, Colombia. Resultados: El promedio de edad fue de 59.8 años, el tiempo de evolución de la enfermedad fue de 2.7 años, la variante más frecuente fue la comportamental, la alteración más frecuente en la RMN fue la atrofia frontotemporal y en el SPECT fue la hipoperfusión frontotemporal. El hallazgo más importante fue el rendimiento normal del 61.9% de los pacientes en pruebas de praxis, la cual se relacionó con alteración en la perfusión temporo parietal en el SPECT (p <0.02. El minimental ni el clox sirvieron como pruebas de tamizaje

  15. Episodic Memory in Alzheimer Disease, Frontotemporal Dementia, and Dementia With Lewy Bodies/Parkinson Disease Dementia: Disentangling Retrieval From Consolidation.

    Science.gov (United States)

    Economou, Alexandra; Routsis, Christopher; Papageorgiou, Sokratis G

    2016-01-01

    Differences in episodic memory performance in patients with Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB)/Parkinson disease with dementia (PDD) are inconsistent and task dependent. The inconsistencies may be attributed to the different tasks drawing on different memory processes. Few studies have examined episodic memory impairment in the above groups using memory tests that facilitate encoding, to distinguish memory deficits due to impairment of specific processes. We examined the memory performance of 106 AD patients, 51 FTD patients, 26 DLB/PDD patients, and 37 controls using the Five-Words Test, a 5-item memory test that facilitates encoding. The patient groups did not differ in modified Mini Mental State Examination scores. AD patients scored lowest on the Five-Words Test overall, and showed the greatest reduction from immediate total recall to delayed free recall relative to the other 2 groups, consistent with a predominantly consolidation deficit. DLB/PDD patients showed the largest improvement from delayed free to delayed total recall relative to the other 2 groups, consistent with a predominantly retrieval deficit. Deficits in both consolidation and retrieval underlie the memory impairment of the patients, to different extents, and contribute to the theoretical understanding of the nature of the memory impairment of the patient groups.

  16. Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17

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    Pickering-Brown Stuart

    2006-08-01

    Full Text Available Abstract Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17 is an autosomal dominant neurodegenerative disorder, which has three cardinal features: behavioral and personality changes, cognitive impairment, and motor symptoms. FTDP-17 was defined during the International Consensus Conference in Ann Arbor, Michigan, in 1996. The prevalence and incidence remain unknown but FTDP-17 is an extremely rare condition. It is caused by mutations in the tau gene, which encodes a microtubule-binding protein. Over 100 families with 38 different mutations in the tau gene have been identified worldwide. The phenotype of FTDP-17 varies not only between families carrying different mutations but also between and within families carrying the same mutations. The pathogenetic mechanisms underlying the disorder are thought to be related to the altered proportion of tau isoforms or to the ability of tau to bind microtubules and to promote microtubule assembly. Definitive diagnosis of FTDP-17 requires a combination of characteristic clinical and pathological features and molecular genetic analysis. Genetic counseling should be offered to affected and at-risk individuals; for most subtypes, penetrance is incomplete. Currently, treatment for FTDP-17 is only symptomatic and supportive. The prognosis and rate of the disease's progression vary considerably among individual patients and genetic kindreds, ranging from life expectancies of several months to several years, and, in exceptional cases, as long as two decades.

  17. In vivo amyloid imaging with PET in frontotemporal dementia

    Energy Technology Data Exchange (ETDEWEB)

    Engler, Henry [Uruguay University Hospital of Clinics and Faculty of Science, Department of Nuclear Medicine, Montevideo (Uruguay); Uppsala University Hospital, Department of Nuclear Medicine, Uppsala (Sweden); Uppsala University, Department of Medical Sciences, Uppsala (Sweden); GE Healthcare, Uppsala Imanet, Uppsala (Sweden); Santillo, Alexander F.; Lindau, Maria; Lannfelt, Lars; Kilander, Lena [Uppsala University, Department of Public Health and Caring Sciences/Geriatrics, Uppsala (Sweden); Wang, Shu Xia [Guangdong Provincial People' s Hospital, Weilun PET Centre, Guangzhou (China); Savitcheva, Irina [Uppsala University Hospital, Department of Nuclear Medicine, Uppsala (Sweden); Nordberg, Agneta [Karolinska Institute, Division of Molecular Neuropharmacology, Stockholm (Sweden); Karolinska University Hospital Huddinge, Department of Geriatric Medicine, Stockholm (Sweden); Laangstroem, Bengt [GE Healthcare, Uppsala Imanet, Uppsala (Sweden); Uppsala University, Departments of Biochemistry and Organic Chemistry, Uppsala (Sweden)

    2008-01-15

    N-methyl[11C]2-(4'methylaminophenyl)-6-hydroxy-benzothiazole (PIB) is a positron emission tomography (PET) tracer with amyloid binding properties which allows in vivo measurement of cerebral amyloid load in Alzheimer's disease (AD). Frontotemporal dementia (FTD) is a syndrome that can be clinically difficult to distinguish from AD, but in FTD amyloid deposition is not a characteristic pathological finding. The aim of this study is to investigate PIB retention in FTD. Ten patients with the diagnosis of FTD participated. The diagnosis was based on clinical and neuropsychological examination, computed tomography or magnetic resonance imaging scan, and PET with 18Fluoro-2-deoxy-d-glucose (FDG). The PIB retention, measured in regions of interest, was normalised to a reference region (cerebellum). The results were compared with PIB retention data previously obtained from 17 AD patients with positive PIB retention and eight healthy controls (HC) with negative PIB retention. Statistical analysis was performed with a students t-test with significance level set to 0.00625 after Bonferroni correction. Eight FTD patients showed significantly lower PIB retention compared to AD in frontal (p < 0.0001), parietal (p < 0.0001), temporal (p = 0.0001), and occipital (p = 0.0003) cortices as well as in putamina (p < 0.0001). The PIB uptake in these FTD patients did not differ significantly from the HC in any region. However, two of the 10 FTD patients showed PIB retention similar to AD patients. The majority of FTD patients displayed no PIB retention. Thus, PIB could potentially aid in differentiating between FTD and AD. (orig.)

  18. Neuropathological aspects of Alzheimer disease, Parkinson disease and frontotemporal dementia.

    Science.gov (United States)

    Jellinger, Kurt A

    2008-01-01

    Proteinopathies are a heterogenous group of neurodegenerative disorders, characterized by intra- and extracellular accumulation of abnormal filament proteins. To describe the neuropathology of specific forms of tauopathies and synucleinopathies, the overlap of morphologic features and molecular interactions. The study uses currently available morphologic criteria of different proteinopathies. Alzheimer disease (AD) is featured by deposition of beta-amyloid peptides, phosphorylated tau protein (3- and 4-repeat tau) and frequent alpha-synuclein (aSyn) deposits. Lewy body diseases (LBD), such as sporadic Parkinson disease (PD) and dementia with Lewy bodies (DLB), show aSyn-positive deposits in neurons, neurites, glia, and presynaptic terminals, while frontotemporal dementias present tau-positive and tau-negative, ubiquitin- and TDP-43-positive neuronal and glial inclusions. The latter have also been observed in AD, PD, PD dementia and motor neuron disorders. Molecular interactions between major proteins, which may occur within the same brain in various distribution patterns, cause variable phenotypes and mixed pathologies, e.g. AD with aSyn pathology in the brainstem and amygdala, PD and DLB with AD lesions, and frontotemporal dementia with a mixture of various deposits, while others are featured by one principal pathology without other lesions (e.g. tangle-predominant type of dementia, pure PD, brainstem-predominant LBD). Animal models and in vitro studies showing co-occurrence and mutual promotion of fibrillation of these proteins indicate their synergistic interactions in the pathogenesis of these disorders which, at least in part, are genetically influenced. 2008 S. Karger AG, Basel

  19. Criminal behavior in frontotemporal dementia and Alzheimer disease.

    Science.gov (United States)

    Liljegren, Madeleine; Naasan, Georges; Temlett, Julia; Perry, David C; Rankin, Katherine P; Merrilees, Jennifer; Grinberg, Lea T; Seeley, William W; Englund, Elisabet; Miller, Bruce L

    2015-03-01

    Neurodegenerative diseases can cause dysfunction of neural structures involved in judgment, executive function, emotional processing, sexual behavior, violence, and self-awareness. Such dysfunctions can lead to antisocial and criminal behavior that appears for the first time in the adult or middle-aged individual or even later in life. To investigate the frequency and type of criminal behavior among patients with a diagnosed dementing disorder. We conducted a retrospective medical record review of 2397 patients who were seen at the University of California, San Francisco, Memory and Aging Center between 1999 and 2012, including 545 patients with Alzheimer disease (AD), 171 patients with behavioral variant of frontotemporal dementia (bvFTD), 89 patients with semantic variant of primary progressive aphasia, and 30 patients with Huntington disease. Patient notes containing specific keywords denoting criminal behavior were reviewed. Data were stratified by criminal behavior type and diagnostic groups. Frequencies of criminal behavior and χ² statistics were calculated. Of the 2397 patients studied, 204 (8.5%) had a history of criminal behavior that emerged during their illness. Of the major diagnostic groups, 42 of 545 patients (7.7%) with AD, 64 of 171 patients (37.4%) with bvFTD, 24 of 89 patients (27.0%) with semantic variant of primary progressive aphasia, and 6 of 30 patients (20%) with Huntington disease exhibited criminal behavior. A total of 14% of patients with bvFTD were statistically significantly more likely to present with criminal behavior compared with 2% of patients with AD (P advances, trespassing, and public urination in contrast with those in the AD group, who commonly committed traffic violations, often related to cognitive impairment. Criminal behavior is more common in patients with bvFTD and semantic variant of primary progressive aphasia than in those with AD and is more likely to be an early manifestation of the disorder. Judicial

  20. Dementia Apraxia Test (DATE): A Brief Tool to Differentiate Behavioral Variant Frontotemporal Dementia from Alzheimer's Dementia Based on Apraxia Profiles.

    Science.gov (United States)

    Johnen, Andreas; Frommeyer, Jana; Modes, Fenja; Wiendl, Heinz; Duning, Thomas; Lohmann, Hubertus

    2016-01-01

    Standardized praxis assessments with modern, empirically validated screening tests have substantially improved clinical evaluation of apraxia in patients with stroke. Although apraxia may contribute to early differential diagnosis of Alzheimer's dementia (AD) and behavioral variant frontotemporal dementia (bvFTD), no comparable test is readily available to clinicians for this purpose to date. To design a clinically useful apraxia test for the differentiation of AD and bvFTD. 84 test items pertaining to twelve praxis subdomains were evaluated for their efficacy to discriminate between patients with bvFTD (n = 24), AD (n = 28), and elderly healthy controls (HC; n = 35). Items were then selected based on discriminative value and psychometric properties. Items indicative of mild AD comprised spatially complex imitation of hand and finger postures and to a lesser degree, pantomime of common object-use. Buccofacial apraxia including imitation of face postures, emblematic face postures, and repetition of multisyllabic pseudowords differentiated bvFTD from HC and AD. The final test version consisting of 20 items proved highly efficient for the discrimination of biologically confirmed dementia patients from HC (sensitivity 91% , specificity 71%) but also for differential diagnosis of bvFTD and AD (sensitivity 74% , specificity 93%). Assessment of praxis profiles effectively contributes to diagnosis and differential diagnosis of AD and bvFTD. The Dementia Apraxia Test (DATE) is a brief and easy to administer cognitive tool for dementia assessment, has a high inter-rater reliability (Cohen's κ= 0.885) and demonstrates content validity.

  1. Loss of exosomes in progranulin-associated frontotemporal dementia.

    Science.gov (United States)

    Benussi, Luisa; Ciani, Miriam; Tonoli, Elisa; Morbin, Michela; Palamara, Luisa; Albani, Diego; Fusco, Federica; Forloni, Gianluigi; Glionna, Michela; Baco, Monika; Paterlini, Anna; Fostinelli, Silvia; Santini, Benedetta; Galbiati, Elisabetta; Gagni, Paola; Cretich, Marina; Binetti, Giuliano; Tagliavini, Fabrizio; Prosperi, Davide; Chiari, Marcella; Ghidoni, Roberta

    2016-04-01

    Many cells of the nervous system have been shown to release exosomes, a subclass of secreted vesicles of endosomal origin capable of transferring biomolecules among cells: this transfer modality represents a novel physiological form of intercellular communication between neural cells. Herein, we demonstrated that progranulin (PGRN), a protein targeted to the classical secretory pathway, is also secreted in association with exosomes by human primary fibroblasts. Moreover, we demonstrated that null mutations in the progranulin gene (GRN), a major cause of frontotemporal dementia, strongly reduce the number of released exosomes and alter their composition. In vitro GRN silencing in SHSY-5Y cells confirmed a role of PGRN in the control of exosome release. It is believed that depletion of PGRN in the brain might cause neurodegeneration in GRN-associated frontotemporal dementia. We demonstrated that, along with shortage of the circulating PGRN, GRN null mutations alter intercellular communication. Thus, a better understanding of the role played by exosomes in GRN-associated neurodegeneration is crucial for the development of novel therapies for these diseases.

  2. Hippocampal sclerosis dementia: An amnesic variant of frontotemporal degeneration

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    Chiadi U. Onyike

    Full Text Available ABSTRACT Objective: To describe characteristics of hippocampal sclerosis dementia. Methods: Convenience sample of Hippocampal sclerosis dementia (HSD recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization. Results: The cases showed atrophy and neuronal loss localized to the hippocampus, amygdala and entorrhinal cortex. The majority (79.2% had amnesia at illness onset, and many (54.2% showed abnormal conduct and psychiatric disorder. Nearly 42% presented with an amnesic state, and 37.5% presented with amnesia plus abnormal conduct and psychiatric disorder. All eventually developed a behavioral or psychiatric disorder. Disorientation, executive dysfunction, aphasia, agnosia and apraxia were uncommon at onset. Alzheimer disease (AD was the initial clinical diagnosis in 89% and the final clinical diagnosis in 75%. Diagnosis of frontotemporal dementia (FTD was uncommon (seen in 8%. Conclusion: HSD shows pathological characteristics of FTD and clinical features that mimic AD and overlap with FTD. The findings, placed in the context of earlier work, support the proposition that HSD belongs to the FTD family, where it may be identified as an amnesic variant.

  3. Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer's disease

    NARCIS (Netherlands)

    A. Hafkemeijer (Anne); C. Möller (Christiane); E.G.P. Dopper (Elise); L.C. Jiskoot (Lize); T.M. Schouten (Tijn M.); J.C. van Swieten (John); W.M. van der Flier (Wiesje); H. Vrenken (Hugo); Y. Pijnenburg (Yolande); F. Barkhof (Frederik); P. Scheltens (Philip); J. van der Grond (Jeroen); S.A.R.B. Rombouts (Serge)

    2015-01-01

    textabstractIntroduction: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. Early differentiation between both types of dementia may be challenging due to heterogeneity and overlap of symptoms. Here, we apply resting st

  4. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease.

    Science.gov (United States)

    Goetzl, Edward J; Kapogiannis, Dimitrios; Schwartz, Janice B; Lobach, Iryna V; Goetzl, Laura; Abner, Erin L; Jicha, Gregory A; Karydas, Anna M; Boxer, Adam; Miller, Bruce L

    2016-12-01

    Synaptic dysfunction occurs early in senile dementias, presumably as a result of decreased levels of functional synaptic proteins as found in autopsied brains of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD). Plasma neuronal-derived exosomes (NDEs) were recovered by precipitation and immunoabsorption from 12 patients with AD, 16 with FTD, and 28 controls in a cross-sectional study, and from 9 patients with AD, 10 with FTD, and 19 controls in a longitudinal study. Six synaptic proteins in NDE extracts were quantified by ELISAs and normalized for exosome amounts. NDE levels of synaptophysin, synaptopodin, synaptotagmin-2, and neurogranin were significantly lower in patients with FTD and AD than in controls, but those of growth-associated protein 43 and synapsin 1 were reduced only in patients with AD. Functionally relevant phosphorylation of synapsin 1 serine 9 was reduced in patients with FTD and AD, although total synapsin 1 protein was higher in FTD than in controls. NDE levels of synaptotagmin, synaptophysin, and neurogranin were decreased years before dementia in patients with FTD and AD. NDE levels of synaptopodin, synaptotagmin, and synaptophysin, but not of amyloid β-peptide 42 or P-T181-tau, were correlated significantly with cognition assessed by mini-mental state examination or AD assessment scale-cognitive subscale. NDE synaptic proteins may be useful preclinical indices and progression measures in senile dementias.-Goetzl, E. J., Kapogiannis, D., Schwartz, J. B., Lobach, I. V., Goetzl, L., Abner, E. L., Jicha, G. A., Karydas, A. M., Boxer, A., Miller, B. L. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease.

  5. Friedrich Nietzsche's mental illness--general paralysis of the insane vs. frontotemporal dementia.

    Science.gov (United States)

    Orth, M; Trimble, M R

    2006-12-01

    For a long time it was thought that Nietzsche suffered from general paralysis of the insane (GPI). However, this diagnosis has been questioned recently, and alternative diagnoses have been proposed. We have charted Friedrich Nietzsche's final fatal illness, and viewed the differential diagnosis in the light of recent neurological understandings of dementia syndromes. It is unclear that Nietzsche ever had syphilis. He lacked progressive motor and other neurological features of a progressive syphilitic central nervous system (CNS) infection and lived at least 12 years following the onset of his CNS signs, which would be extremely rare for patients with untreated GPI. Finally, his flourish of productivity in 1888 would be quite uncharacteristic of GPI, but in keeping with reports of burgeoning creativity at some point in the progression of frontotemporal dementia (FTD). We suggest that Nietzsche did not have GPI, but died from a chronic dementia, namely FTD.

  6. Common Molecular Pathways in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

    Science.gov (United States)

    Weishaupt, Jochen H; Hyman, Tony; Dikic, Ivan

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative diseases in which predominantly motor neurons and cerebral cortex neurons, respectively, are affected. Several novel ALS and FTD disease genes have been recently discovered, pointing toward a few overarching pathways in ALS/FTD pathogenesis. Nevertheless, a precise picture of how various cellular processes cause neuronal death, or how different routes leading to ALS and FTD are functionally connected is just emerging. Moreover, how the most recent milestone findings in the ALS/FTD field might lead to improved diagnosis and treatment is actively being explored. We highlight some of the most exciting recent topics in the field, which could potentially facilitate the identification of further links between the pathogenic ALS/FTD pathways related to autophagy, vesicle trafficking, and RNA metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Relearning knowledge for people in a case of right variant frontotemporal dementia.

    Science.gov (United States)

    Suárez-González, Aida; Crutch, Sebastian J

    2016-01-01

    Right variant frontotemporal dementia (Rvt-FTD) is a rare variant of FTD that usually presents with a progressive difficulty in recognizing familiar people. We aimed to determine whether rehabilitation of semantic knowledge for people improves recognition by both verbal and visual channels in a patient with Rvt-FTD. Knowledge for 21 famous people was assessed in a patient with Rvt-FTD before and after completing a semantic rehabilitation program. After rehabilitation recognition increased by 95% when presented with the famous people's names and related semantic facts, but only by 28% when presented with their faces. Recognition of people by verbal and visual channels improves differently after semantic knowledge rehabilitation.

  8. Clinic, neuropathology and molecular genetics of frontotemporal dementia: a mini-review

    OpenAIRE

    Pan, Xiao-Dong; Chen, Xiao-Chun

    2013-01-01

    Frontotemporal lobar degeneration (FTLD) represents a group of clinically, neuropathologically and genetically heterogeneous disorders with plenty of overlaps between the neurodegenerative mechanism and the clinical phenotype. FTLD is pathologically characterized by the frontal and temporal lobar atrophy. Frontotemporal dementia (FTD) clinically presents with abnormalities of behavior and personality and language impairments variants. The clinical spectrum of FTD encompasses distinct canonica...

  9. Late life bipolar disorder evolving into frontotemporal dementia mimic

    Directory of Open Access Journals (Sweden)

    Dols A

    2016-09-01

    Full Text Available Annemiek Dols,1 Welmoed Krudop,2 Christiane Möller,2 Kenneth Shulman,3 Martha Sajatovic,4 Yolande AL Pijnenburg2 1Department of Old Age Psychiatry, GGZInGeest, 2Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, the Netherlands; 3Department of Geriatric Psychiatry, Sunnybrook Health Science Centre, Faculty of Medicine, University of Toronto, Toronto, Canada; 4Department of Psychiatry and Neurology, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA Objectives: Although bipolar disorder has been understood classically as a cyclic disease with full recovery between mood episodes, in the last decade, evidence has accumulated supporting progressive features. The clinical picture of advanced or end-stage bipolar disorder is heterogeneous with possible deficits in cognition and behavior, as illustrated by our case series.Cases: From our neuropsychiatric outpatient clinic, we describe four cases with bipolar disorder gradually developing a clinical syndrome, including apathy, disinhibition, loss of empathy, stereotypical behavior, and compulsiveness, fulfilling the criteria for possible behavioral variant frontotemporal dementia. All cases were diagnosed with bipolar 1 disorder at least 10 years before the onset of the current symptoms, which were not due to recent mood episodes or switches of medication. In all cases, 3–7 years of follow-up yielded no progression. Repeated neuroimaging was within normal limits. Cerebrospinal fluid biomarker studies were not supportive of underlying neurodegenerative pathology. C9orf72 mutation status was negative in all cases.Conclusion: Symptoms fitting the criteria for possible behavioral variant frontotemporal dementia may be present in end-stage of bipolar disorder. An alternative neurodegenerative nature seems unlikely based on repeated normal neuroimaging and the absence of clinical

  10. Demência fronto-temporal: aspectos clínicos e terapêuticos Demencia frontotemporal: aspectos clínicos y terapéuticos Frontotemporal dementia: clinical and therapeutic features

    Directory of Open Access Journals (Sweden)

    Antônio Lúcio Teixeira-Jr

    2006-04-01

    Full Text Available A demência fronto-temporal é uma importante causa de demência no período pré-senil. Caracteriza-se por significativas modificações do comportamento e da personalidade, enquanto o funcionamento cognitivo avaliado por testes psicométricos tradicionais encontra-se relativamente preservado. Muitos pacientes buscam o psiquiatra em virtude dos sintomas comportamentais proeminentes, como apatia, desinibição e comportamentos perseverativos ou estereotipados. O tratamento racional da demência fronto-temporal é atualmente limitado. Os sintomas comportamentais são controlados principalmente por inibidores seletivos da recaptação de serotonina.La demencia frontotemporal es una importante causa de demencia en el período presenil de la vida. Se caracteriza por alteraciones significativas en el comportamiento y en la personalidad, mientras la función cognitiva evaluada por pruebas psicométricas convencionales resulta relativamente preservada. Muchos pacientes recurren al psiquiatra en función de síntomas comportamentales sobresalientes como apatía, desinhibición y comportamientos perseverantes o estereotipados. El tratamiento racional de la demencia frontotemporal aún se encuentra bastante limitado. Los síntomas comportamentales se controlan principalmente con inhibidores selectivos de la recaptación de serotonina.Frontotemporal dementia is a major cause of dementia in the presenium. It is characterized by significant changes in behavior and personality, while cognitive functioning as assessed by traditional psychometric tests is relatively preserved. Thus, many patients present to the psychiatrist because of the prominence of behavioral symptoms, such as apathy, disinhibition, perseverative or stereotyped behaviors. Rational treatment for frontotemporal dementia is currently limited. The behavioral symptoms are controlled mainly with selective serotonin reuptake inhibitors.

  11. Predicting behavioral variant frontotemporal dementia with pattern classification in multi-center structural MRI data.

    Science.gov (United States)

    Meyer, Sebastian; Mueller, Karsten; Stuke, Katharina; Bisenius, Sandrine; Diehl-Schmid, Janine; Jessen, Frank; Kassubek, Jan; Kornhuber, Johannes; Ludolph, Albert C; Prudlo, Johannes; Schneider, Anja; Schuemberg, Katharina; Yakushev, Igor; Otto, Markus; Schroeter, Matthias L

    2017-01-01

    Frontotemporal lobar degeneration (FTLD) is a common cause of early onset dementia. Behavioral variant frontotemporal dementia (bvFTD), its most common subtype, is characterized by deep alterations in behavior and personality. In 2011, new diagnostic criteria were suggested that incorporate imaging criteria into diagnostic algorithms. The study aimed at validating the potential of imaging criteria to individually predict diagnosis with machine learning algorithms. Brain atrophy was measured with structural magnetic resonance imaging (MRI) at 3 Tesla in a multi-centric cohort of 52 bvFTD patients and 52 healthy control subjects from the German FTLD Consortium's Study. Beside group comparisons, diagnosis bvFTD vs. controls was individually predicted in each subject with support vector machine classification in MRI data across the whole brain or in frontotemporal, insular regions, and basal ganglia known to be mainly affected based on recent meta-analyses. Multi-center effects were controlled for with a new method, "leave one center out" conjunction analyses, i.e. repeatedly excluding subjects from each center from the analysis. Group comparisons revealed atrophy in, most consistently, the frontal lobe in bvFTD beside alterations in the insula, basal ganglia and temporal lobe. Most remarkably, support vector machine classification enabled predicting diagnosis in single patients with a high accuracy of up to 84.6%, where accuracy was highest in a region-of-interest approach focusing on frontotemporal, insular regions, and basal ganglia in comparison with the whole brain approach. Our study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.

  12. Translation, cross-cultural adaptation and applicability of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS

    Directory of Open Access Journals (Sweden)

    Thais Bento Lima-Silva

    Full Text Available ABSTRACT Background: Staging scales for dementia have been devised for grading Alzheimer's disease (AD but do not include the specific symptoms of frontotemporal lobar degeneration (FTLD. Objective: To translate and adapt the Frontotemporal Dementia Rating Scale (FTD-FRS to Brazilian Portuguese. Methods: The cross-cultural adaptation process consisted of the following steps: translation, back-translation (prepared by independent translators, discussion with specialists, and development of a final version after minor adjustments. A pilot application was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for disease severity (CDR=1.0. The evaluation protocol included: Addenbrooke's Cognitive Examination-Revised (ACE-R, Mini-Mental State Examination (MMSE, Executive Interview (EXIT-25, Neuropsychiatric Inventory (NPI, Frontotemporal Dementia Rating Scale (FTD-FRS and Clinical Dementia Rating scale (CDR. Results: The Brazilian version of the FTD-FRS seemed appropriate for use in this country. Preliminary results revealed greater levels of disability in bvFTD than in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild, 63.64% moderate. It appears that the CDR underrates disease severity in bvFTD since a relevant proportion of patients rated as having mild dementia (CDR=1.0 in fact had moderate or severe levels of disability according to the FTD-FRS. Conclusion: The Brazilian version of the FTD-FRS seems suitable to aid staging and determining disease progression.

  13. Bilingualism delays the onset of behavioral but not aphasic forms of frontotemporal dementia.

    Science.gov (United States)

    Alladi, Suvarna; Bak, Thomas H; Shailaja, Mekala; Gollahalli, Divyaraj; Rajan, Amuya; Surampudi, Bapiraju; Hornberger, Michael; Duggirala, Vasanta; Chaudhuri, Jaydip Ray; Kaul, Subhash

    2017-03-18

    Bilingualism has been found to delay onset of dementia and this has been attributed to an advantage in executive control in bilinguals. However, the relationship between bilingualism and cognition is complex, with costs as well as benefits to language functions. To further explore the cognitive consequences of bilingualism, the study used Frontotemporal dementia (FTD) syndromes, to examine whether bilingualism modifies the age at onset of behavioral and language variants of Frontotemporal dementia (FTD) differently. Case records of 193 patients presenting with FTD (121 of them bilingual) were examined and the age at onset of the first symptoms were compared between monolinguals and bilinguals. A significant effect of bilingualism delaying the age at onset of dementia was found in behavioral variant FTD (5.7 years) but not in progressive nonfluent aphasia (0.7 years), semantic dementia (0.5 years), corticobasal syndrome (0.4 years), progressive supranuclear palsy (4.3 years) and FTD-motor neuron disease (3 years). On dividing all patients predominantly behavioral and predominantly aphasic groups, age at onset in the bilingual behavioral group (62.6) was over 6 years higher than in the monolingual patients (56.5, p=0.006), while there was no difference in the aphasic FTD group (60.9 vs. 60.6 years, p=0.851). The bilingual effect on age of bvFTD onset was shown independently of other potential confounding factors such as education, gender, occupation, and urban vs rural dwelling of subjects. To conclude, bilingualism delays the age at onset in the behavioral but not in the aphasic variants of FTD. The results are in line with similar findings based on research in stroke and with the current views of the interaction between bilingualism and cognition, pointing to advantages in executive functions and disadvantages in lexical tasks.

  14. The genetics of dementias. Part 1: Molecular basis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17

    Directory of Open Access Journals (Sweden)

    Anna Kowalska

    2009-06-01

    Full Text Available Frontotemporal dementia (FTD, characterized by neurodegeneration mainly in the frontal and temporal lobes, accounts for ca. 10–15�0of all dementias. In 1892 the Czech-German neuropsychiatrist Arnold Pick reported the first case of FTD in a 71-year-old patient suffering from progressive dementia, memory disturbances, and aphasia associated with frontal and temporal lobe atrophy and the presence of neuronal inclusions. Later the inclusions were named Pick bodies. The neuropathological hallmark of FTD is very differentiated. In contrast to Alzheimer’s disease (AD, there are neither senile plaques nor neurofibrillary tangles in the brains of FTD patients. Frontotemporal dementias are tauopathies, a group of disorders caused by aberrant metabolism of tau protein, a family of proteins associated with microtubules (MAPT: macrotubule-associated tau protein. In the nervous system the protein stabilizes microtubules in neuronal axons and is thus responsible for crucial processes in neuron metabolism, such as signal transduction, plasticity, and intracellular transport. In the human brain, six isoforms are produced from the MAPT gene (chromosome 17 q21.2 by alternative mRNA splicing. The isoforms differ in the number of amino acids in the protein chain, the presence of three (3R tau type or four (4R tau type domains responsible for binding to microtubules, and one or two inserts containing from 29 to 58 amino acids. The isoforms are modified posttranslationally by hyperphosphorylation, glycation, or oxidation, which can change the protein’s properties and disturb its normal function. Altered metabolism of tau protein changes its interactions with tubulin, leading to destabilization of the microtubule structure and initiating the generation of toxic tau aggregates. The first mutations in the MAPT gene responsible for frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17 were found in 1998. So far over 40 mutations in the MAPT

  15. Frontotemporal dementia with severe thalamic involvement : a clinical and neuropathological study

    Directory of Open Access Journals (Sweden)

    Radanovic Márcia

    2003-01-01

    Full Text Available Frontotemporal dementia (FTD is the third-leading cause of cortical dementia after Alzheimer's disease and Lewy body dementia, and is characterized by a dementia where behavioral disturbances are prominent and appear early in the course of the disease. We report the case of a 58 year-old man affected by dementia with behavioral disturbances, in addition to rigid-hypokinetic and a lower motor neuron syndrome that were present at later stages of the illness. Neuroimaging studies showed frontotemporal atrophy. Neuropathological studies revealed intense thalamic neuronal loss and astrocytic gliosis, as well as moderate frontotemporal neuronal loss, astrocytosis and spongiform degeneration. Thalamic degeneration has previously been described among the wide group of neuropathological features of FTD. The aim of the present study is to show the clinical and neuropathological aspects of thalamic degeneration in FTD, along with its role in behavioral disturbances, a common finding in this condition.

  16. Mouse models of frontotemporal dementia: A comparison of phenotypes with clinical symptomatology.

    Science.gov (United States)

    Ahmed, Rebekah M; Irish, Muireann; van Eersel, Janet; Ittner, Arne; Ke, Yazi D; Volkerling, Alexander; van der Hoven, Julia; Tanaka, Kimi; Karl, Tim; Kassiou, Michael; Kril, Jillian J; Piguet, Olivier; Götz, Jürgen; Kiernan, Matthew C; Halliday, Glenda M; Hodges, John R; Ittner, Lars M

    2017-03-01

    Frontotemporal dementia (FTD) is the second most common cause of young onset dementia. It is increasingly recognized that there is a clinical continuum between FTD and amyotrophic lateral sclerosis (ALS). At a clinical, pathological and genetic level there is much heterogeneity in FTD, meaning that our understanding of this condition, pathophysiology and development of treatments has been limited. A number of mouse models focusing predominantly on recapitulating neuropathological and molecular changes of disease have been developed, with most transgenic lines expressing a single specific protein or genetic mutation. Together with the species-typical presentation of functional deficits, this makes the direct translation of results from these models to humans difficult. However, understanding the phenotypical presentations in mice and how they relate to clinical symptomology in humans is essential for advancing translation. Here we review current mouse models in FTD and compare their phenotype to the clinical presentation in patients.

  17. Three patients with mood disorders showing catatonia and frontotemporal lobes atrophy.

    Science.gov (United States)

    Utumi, Yushi; Iseki, Eizo; Arai, Heii

    2013-12-01

    Here we report the cases of three patients with mood disorders showing catatonia and frontotemporal lobe atrophy. Catatonia is a syndrome linked to frontal dysfunction that most frequently occurs in patients with mood disorders. The diagnostic criteria of catatonia and frontotemporal dementia partly overlap. In the present patients, catatonia might be closely related to frontal dysfunction caused by frontotemporal lobe atrophy. With regard to therapeutics for catatonia, we found that administering a low dose of lorazepam alone or after electroconvulsive therapy may be useful for treating and preventing catatonia. We also found that administering glutaminate antagonists such as memantine may be useful for treating lorazepam-resistant catatonia.

  18. In search of autobiographical memories: A PET study in the frontal variant of frontotemporal dementia.

    Science.gov (United States)

    Piolino, Pascale; Chételat, Gaël; Matuszewski, Vanessa; Landeau, Brigitte; Mézenge, Florence; Viader, Fausto; de la Sayette, Vincent; Eustache, Francis; Desgranges, Béatrice

    2007-09-20

    Patients suffering from frontal variant of frontotemporal dementia (fv-FTD) undergo autobiographical amnesia encompassing all time periods. We previously demonstrated in a group of 20 fv-FTD patients that this impairment involved deficits in executive function and semantic memory for all periods as well as new episodic learning and behavioural changes for the most recent period covering the last 12 months [Matuszewski, V., Piolino, P., de la Sayette, V., Lalevée, C., Pélerin, A., Dupuy, B., et al. (2006). Retrieval mechanisms for autobiographical memories: Insights from the frontal variant of frontotemporal dementia, Neuropsychologia, 44, 2386-2397]. The aim of the present study was to unravel the neural bases of this impairment by mapping in a subgroup of patients correlations between resting-state brain glucose utilization measured by FDG-PET and measures of autobiographical memory (AM) using the TEMPau task which is designed to gauge personal event recollection across five life time periods. Like in our previous report, the group of patients was impaired regardless of time periods compared to healthy subjects providing generic memories instead of event specific sensory-perceptual-affective details, i.e., episodic memories. New data showed that the patients were also impaired in sense of reliving and self-perspective during retrieval. The cognitivo-metabolic correlations between the AM score and resting normalized FDG-Uptake were computed using statistical parametric mapping (SPM2) and controlling for age and dementia severity. They revealed that AM deficits were mainly subserved by the dysfunction of left-sided orbitofrontal and also temporal neocortical areas whatever the period. Additional analysis showed that specific memories were associated with left orbitofrontal areas whereas generic memories were mainly associated with the left temporal pole. This study supports the view that fv-FTD patients undergo a breakdown of generative processes which relies

  19. Contextual social cognition and the behavioral variant of frontotemporal dementia.

    Science.gov (United States)

    Ibañez, Agustin; Manes, Facundo

    2012-04-24

    The significance of social situations is commonly context-embedded. Although the role of context has been extensively studied in basic sensory processing or simple stimulus-response settings, its relevance for social cognition is unknown. We propose the social context network model (SCNM), a fronto-insular-temporal network responsible for processing social contextual effects. The SCNM may 1) update the context and use it to make predictions, 2) coordinate internal and external milieus, and 3) consolidate context-target associative learning. We suggest the behavioral variant of frontotemporal dementia (bvFTD) as a specific disorder in which the reported deficits in social cognition (e.g., facial recognition, empathy, decision-making, figurative language, theory of mind) can be described as context impairments due to deficits in the SCNM. Disruption of orbitofrontal-amygdala circuit, as well as the frontal, temporal, and insular atrophy in bVFTD, suggests a relationship between context-sensitive social cognition and SCNM. In considering context as an intrinsic part of social cognition, we highlight the need for a situated cognition approach in social cognition research as opposed to an abstract, universal, and decontextualized approach. The assessment of context-dependent social cognition paradigms, the SCNM, and their possible application to neuropsychiatric disorders may provide new insight into bvFTD and other related frontal disorders.

  20. Shared neural correlates of limb apraxia in early stages of Alzheimer's dementia and behavioural variant frontotemporal dementia.

    Science.gov (United States)

    Johnen, Andreas; Brandstetter, Lisa; Kärgel, Christian; Wiendl, Heinz; Lohmann, Hubertus; Duning, Thomas

    2016-11-01

    Limb apraxia denotes a cognitive impairment of gesture production. Lesion studies in patients with stroke point towards distinct neural processing streams for limb imitation and object-pantomime within left parietal and temporal cortex, respectively. Despite its frequent occurrence as an early symptom in both, Alzheimer's dementia (AD) and behavioural variant frontotemporal dementia (bvFTD), neural correlates of limb apraxia within these patient groups remain unexplored. Using voxel-based morphometry and multiple regression models, associations between limb apraxia and gray matter (GM) volume were investigated in 36 dementia patients (18 AD, 18 bvFTD) in early disease stages. Both dementia subtypes showed a comparable degree of limb apraxia. Although the patient groups showed distinct atrophy patterns with significantly more severe frontal GM loss in bvFTD, we found similar neural correlates of limb apraxia within posterior brain regions for both dementia subtypes: limb-imitation was associated with bilateral atrophy of superior, inferior and medial parietal cortex. Object-pantomime showed associations with GM volume in right middle temporal and angular gyrus. Our results argue for shared neural correlates of limb apraxia in AD and bvFTD and validate the syndrome as an important neuropsychological feature across different etiologies. Moreover, our results are compatible with neural models derived from patients with stroke, suggesting partly distinct neural representations of imitation and pantomime. Compared to patients with stroke however, AD and bvFTD showed more bilateral or even right lateralized neural representations of limb apraxia, proposing a greater influence of visuospatial impairments and spatial body representation deficits on praxis performance.

  1. Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation

    DEFF Research Database (Denmark)

    Rohrer, Jonathan D; Ahsan, R Laila; Isaacs, Adrian M;

    2009-01-01

    BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease. There are no ......BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease....... There are no detailed studies of brain imaging in CHMP2B mutation-associated FTD. This study aimed to investigate whether there were early or presymptomatic changes in this group of patients. METHODS: Subjects comprised 16 members of a Danish family with CHMP2B mutation-associated FTD. Nine subjects were presymptomatic...... mutation carriers with a control group of 7 mutation-negative family members. Volumetric MRI brain scans were performed on all subjects at two time points, and rates of volume change were compared between the two groups. RESULTS: We demonstrate that generalized atrophy occurs presymptomatically in CHMP2B...

  2. Convergent grey and white matter evidence of orbitofrontal cortex changes related to disinhibition in behavioural variant frontotemporal dementia.

    Science.gov (United States)

    Hornberger, Michael; Geng, John; Hodges, John R

    2011-09-01

    Disinhibition is a common behavioural symptom in frontotemporal dementia but its neural correlates are still debated. In the current study, we investigated the grey and white matter neural correlates of disinhibition in a sample of behavioural variant frontotemporal dementia (n = 14) and patients with Alzheimer's disease (n = 15). We employed an objective (Hayling Test of inhibitory functioning) and subjective/carer-based (Neuropsychiatric Inventory) measure of disinhibition to reveal convergent evidence of disinhibitory behaviour. Mean and overlap-based statistical analyses were conducted to investigate profiles of performance in patients with behavioural variant frontotemporal dementia, Alzheimer's disease and controls. Hayling Test and Neuropsychiatric Inventory scores were entered as covariates in a grey matter voxel-based morphometry, as well as in a white matter diffusion tensor imaging analysis to determine the underlying grey and white matter correlates. Patients with behavioural variant frontotemporal dementia showed more disinhibition on both behavioural measures in comparison to patients with Alzheimer's disease and controls. Voxel-based morphometry results revealed that atrophy in orbitofrontal/subgenual, medial prefrontal cortex and anterior temporal lobe areas covaried with total errors score of the Hayling Test. Similarly, the Neuropsychiatric Inventory disinhibition frequency score correlated with atrophy in orbitofrontal cortex and temporal pole brain regions. The orbitofrontal atrophy related to the objective (Hayling Test) and subjective (Neuropsychiatric Inventory) measures of disinhibition was partially overlapping. Diffusion tensor imaging analysis revealed that white matter integrity fractional anisotropy values of the white matter tracts connecting the identified grey matter regions, namely uncinate fasciculus, forceps minor and genu of the corpus callosum, correlated well with the total error score of the Hayling Test. Our results

  3. Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages.

    Directory of Open Access Journals (Sweden)

    Enrico Premi

    Full Text Available OBJECTIVE: Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD, with or without pathogenetic granulin mutations (GRN+ and GRN-, and in presymptomatic GRN mutation carriers (aGRN+. METHODS: Education and occupation attainments were assessed and combined to define Reserve Index (RI in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN, executive network (EN and bilateral frontoparietal networks (FPNs. Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale. RESULTS: In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN. CONCLUSIONS: This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages.

  4. Enhancement of carer skills and patient function in the non-pharmacological management of frontotemporal dementia (FTD): A call for randomised controlled studies

    OpenAIRE

    Claire M.O.'Connor; Lindy Clemson; Thaís Bento Lima da Silva; Olivier Piguet; Hodges, John R.; Eneida Mioshi

    2013-01-01

    ABSTRACT FTD is a unique condition which manifests with a range of behavioural symptoms, marked dysfunction in activities of daily living (ADL) and increased levels of carer burden as compared to carers of other dementias. No efficacious pharmacological interventions to treat FTD currently exist, and research on pharmacological symptom management is variable. The few studies on non-pharmacological interventions in FTD focus on either the carer or the patients' symptoms, and lack methodologica...

  5. The Ekman 60 Faces Test as a diagnostic instrument in frontotemporal dementia.

    Science.gov (United States)

    Diehl-Schmid, Janine; Pohl, Corina; Ruprecht, Carolin; Wagenpfeil, Stefan; Foerstl, Hans; Kurz, Alexander

    2007-05-01

    Frontotemporal dementia (FTD) is characterized by dramatic changes of personality and behaviour. Impaired ability of emotional processing could contribute to these symptoms, as it may lead to misinterpretation of emotional cues that would normally guide behaviour. The aim of the present study was to investigate if the Ekman 60 Faces Test, an instrument to test the recognition of basic facial emotions, enables the differentiation between patients with mild FTD and cognitively healthy subjects (HC). We found that compared to 33 cognitively healthy subjects, 25 patients with mild FTD were impaired in the recognition of basic emotions. At a cut-off score from 46 out of 60 points, the Ekman 60 Faces Test discriminated between patients with mild FTD and HC with 97% diagnostic accuracy (sensitivity: 94%; specificity: 100%). The results of the present study were consistent with the findings of prior studies on smaller patient samples.

  6. Do NIA-AA criteria distinguish Alzheimer's disease from frontotemporal dementia?

    Science.gov (United States)

    Harris, Jennifer M; Thompson, Jennifer C; Gall, Claire; Richardson, Anna M T; Neary, David; du Plessis, Daniel; Pal, Piyali; Mann, David M A; Snowden, Julie S; Jones, Matthew

    2015-02-01

    Clinical criteria are important for improving diagnostic accuracy and ensuring comparability of patient cohorts in research studies. The aim was to assess the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer's disease (AD) dementia in AD and frontotemporal lobar degeneration (FTLD). Two hundred twelve consecutive patients with pathologically confirmed AD or FTLD who were clinically assessed in a specialist cognitive unit were identified. Fifty-five patients were excluded predominantly because of insufficient clinical information. Anonymized clinical data were rated against the NIA-AA criteria by raters who were blinded to clinical and pathologic diagnosis. The NIA-AA AD dementia criteria had a sensitivity of 65.6% for probable and 79.5% for possible AD and a specificity of 95.2% and 94.0% for probable and possible, respectively. In patients with FTLD and predominantly early-onset AD, the NIA-AA AD dementia criteria have high specificity but lower sensitivity. The high specificity is due to the broad exclusion criteria. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  7. Motor neuron disease and frontotemporal dementia: One, two, or three diseases?

    Directory of Open Access Journals (Sweden)

    Bak Thomas

    2010-10-01

    Full Text Available The relationship between motor neurone disease (MND and frontotemporal dementia (FTD has been a topic of scientific exploration for over hundred years. A connection between both diseases was first postulated in 1932 and has been strengthened by a steady stream of case reports since then. By the late 20th century, the link between both diseases was firmly established, with the resulting condition often referred to as MND/FTD. Several strands of evidence support the notion of an MND/FTD overlap. First, a small but well-documented group of patients present with a full-blown FTD, associated with MND. Second, subtle but characteristic changes in frontal-executive functions and social cognition have been described in non-demented MND patients, often in association with frontal atrophy/hypoactivity on neuroimaging. Third, amyotrophic features have been documented in patients primarily diagnosed with FTD. Moreover, the same genetic defect can lead to FTD and MND phenotypes in different members of the same family. However, as the current research is moving toward a more fine-grained evaluation, an increasingly complex picture begins to emerge. Some features, such as psychotic symptoms or severe language deficits (particularly in comprehension and verb processing, seem to occur more often in MND/dementia than in the classical FTD. On the basis of the review of 100 years of literature as well as 10 years of clinical experience of longitudinal follow-up of MND/dementia patients, this review argues in favor of MND/dementia (or, more precisely, MND/dementia/aphasia as a separate clinical entity, not sufficiently explained by a combination of MND and FTD.

  8. Clomipramine in the treatment of compulsive behavior in frontotemporal dementia: a case series.

    Science.gov (United States)

    Furlan, Julio C; Henri-Bhargava, Alexandre; Freedman, Morris

    2014-01-01

    Compulsive behaviors in patients with behavioral variant frontotemporal dementia (bvFTD) occur frequently and are challenging to manage. We report three cases of probable bvFTD associated with compulsive behaviors that responded well to treatment with clomipramine at daily dosages varying from 20 to 175 mg. The titration approach involved an initial 10-mg dose that was subsequently increased in 10 mg increments on a weekly basis until symptom relief without intolerable side effects. Our case series supports the consideration for a therapeutic trial with clomipramine in bvFTD when compulsive behavior occurs in these patients. It also highlights the need for further research on pharmacological treatments in bvFTD.

  9. The Free and Cued Selective Reminding Test Distinguishes Frontotemporal Dementia From Alzheimer's Disease

    Science.gov (United States)

    Lemos, Raquel; Duro, Diana; Simões, Mário R.; Santana, Isabel

    2014-01-01

    Memory impairment is often present in frontotemporal dementia (FTD) as a result of an inefficient use of learning strategies, sometimes leading to a misdiagnosis of Alzheimer's disease (AD). The Free and Cued Selective Reminding Test (FCSRT) is a memory test that controls attention and acquisition, by providing category cues in the learning process. The main goal of this study was to show the usefulness of the FCSRT in the distinction between behavioral (bv-) FTD and AD. Three matched subgroups of participants were considered: bv-FTD (n = 32), AD (n = 32), and a control group of healthy adults (n = 32). Results proved that while AD patients exhibited an overall impairment in FCSRT, bv-FTD subjects showed to benefit more from the controlled learning through category cues. AD patients were 25 times more likely to have an impaired FCSRT. The FCSRT has shown its utility in the distinction between bv-FTD and AD, therefore increasing the diagnostic accuracy. PMID:25062746

  10. Emotional quotient in frontotemporal dementia vs. Alzheimer's disease: the role of socioemotional agnosia.

    Science.gov (United States)

    Carr, Andrew R; Samimi, Mersal S; Paholpak, Pongsatorn; Jimenez, Elvira E; Mendez, Mario F

    2017-01-01

    Socioemotional dysfunction distinguishes behavioural variant frontotemporal dementia (bvFTD) from other dementias. Patients with bvFTD not only have early social impairment and emotional blunting, but they also have agnosia of their socioemotional dysfunction. To investigate the relationship between agnosia and dysfunction, we assessed self-knowledge of socioemotional dysfunction with an emotional quotient (EQ) scale administered to 12 patients with bvFTD and a comparison group of 12 age-matched patients with Alzheimer's disease (AD), and compared these self-ratings to caregiver ratings of social dysfunction and emotional blunting. The bvFTD patients self-rated as having higher EQs than the AD patients, particularly higher self-ratings of their Social Skills, an EQ subscale which correlated with increased emotional blunting. On within-groups analysis, the bvFTD patients' high self-ratings of their EQ Appraisal of Emotions correlated with increased socioemotional dysfunction, whereas all of the AD patients' self-ratings correlated appropriately with their degree of dysfunction. Large socioemotional agnosia scores (EQ minus function) distinguishes bvFTD from AD. Additionally, in bvFTD, agnosia specifically for their ability to appreciate others' emotions correlates with the degree of socioemotional dysfunction, suggesting a role for socioemotional agnosia in increasing socioemotional dysfunction.

  11. Análisis de componentes cognoscitivos y psiquiátricos en pacientes con demencia frontotemporal y alzheimer / Analysis of cognitive and psychiatric components in patients with frontotemporal dementia and Alzheimer

    OpenAIRE

    2010-01-01

    Las enfermedades neurodegenerativas primarias como la Demencia tipo Alzheimer y la Demencia Frontotemporal (DFT) representan un porcentaje importante en la fuente de discapacidad y deterioro en el adulto mayor. Una revisión de la literatura expone tanto similitudes como disparidades entre estas enfermedades tanto en lo genético e histopatológico, como en lo comportamental y cognoscitivo. El objetivo del presente trabajo es caracterizar los componentes cognoscitivos y neuropsiquiátricos altera...

  12. Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease.

    Science.gov (United States)

    Santos, Rodrigo Ribeiro; Torres, Karen C; Lima, Giselle S; Fiamoncini, Carolina M; Mapa, Filipe C; Pereira, Patricia A; Rezende, Vitor B; Martins, Luiza C; Bicalho, Maria A; Moraes, Edgar N; Reis, Helton J; Teixeira, Antonio L; Romano-Silva, Marco A

    2014-01-03

    Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia.

  13. Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Lars Frings

    Full Text Available Behavioural variant frontotemporal dementia (bvFTD and Alzheimer's disease (AD dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct. Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD.

  14. Detailed volumetric analysis of the hypothalamus in behavioral variant frontotemporal dementia.

    Science.gov (United States)

    Bocchetta, Martina; Gordon, Elizabeth; Manning, Emily; Barnes, Josephine; Cash, David M; Espak, Miklos; Thomas, David L; Modat, Marc; Rossor, Martin N; Warren, Jason D; Ourselin, Sebastien; Frisoni, Giovanni B; Rohrer, Jonathan D

    2015-12-01

    Abnormal eating behaviors are frequently reported in behavioral variant frontotemporal dementia (bvFTD). The hypothalamus is the regulatory center for feeding and satiety but its involvement in bvFTD has not been fully clarified, partly due to its difficult identification on MR images. We measured hypothalamic volume in 18 patients with bvFTD (including 9 MAPT and 6 C9orf72 mutation carriers) and 18 cognitively normal controls using a novel optimized multimodal segmentation protocol, combining 3D T1 and T2-weighted 3T MRIs (intrarater intraclass correlation coefficients ≥0.93). The whole hypothalamus was subsequently segmented into five subunits: the anterior (superior and inferior), tuberal (superior and inferior), and posterior regions. The presence of abnormal eating behavior was assessed with the revised version of the Cambridge Behavioural Inventory (CBI-R). The bvFTD group showed a 17% lower hypothalamic volume compared with controls (p hypothalamus.

  15. History, Present, and Progress of Frontotemporal Dementia in China: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Ru-Jing Ren

    2012-01-01

    Full Text Available We aim to provide an overview of clinical and demographical features and neuropathological research on frontotemporal dementia (FTD from China over the past decade. We reviewed the demographic features, clinical presentations, and neuropathology of the FTD-spectrum disorders from the 49 cases in China published since 1998. On the basis of these findings, we retrospect the history and speculate on future progress in terms of FTD in China. We found that most published papers comprise case reports with a few retrospective studies with small sample sizes. Behavior variant FTD (bvFTD was the most common diagnostic subtype, of which 35% were associated with amyotrophic lateral sclerosis or Parkinsonian syndrome. More than 47% patients with FTD had age onset before 65. There were no differences in age of onset and sex distribution between diagnostic subtypes. The spectrum of neuropathological diagnosis of bvFTD was frontotemporal lobe degeneration (FTLD with tau protein or ubiquitin-immunopositive inclusions, and FTLD without intracellular inclusions. Median survival in bvFTD was 14 years. This paper provides an overview of the current status and pointers for future research directions of FTD in China.

  16. Executive Abilities as Reflected by Clock Hand Placement: Frontotemporal Dementia Versus Early-Onset Alzheimer Disease.

    Science.gov (United States)

    Barrows, Robin J; Barsuglia, Joseph; Paholpak, Pongsatorn; Eknoyan, Donald; Sabodash, Valeriy; Lee, Grace J; Mendez, Mario F

    2015-12-01

    The clock-drawing test (CDT) is widely used in clinical practice to diagnose and distinguish patients with dementia. It remains unclear, however, whether the CDT can distinguish among the early-onset dementias. Accordingly, we examined the ability of both quantitative and qualitative CDT analyses to distinguish behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer disease (eAD), the 2 most common neurodegenerative dementias with onset <65 years of age. We hypothesized that executive aspects of the CDT would discriminate between these 2 disorders. The study compared 15 patients with bvFTD and 16 patients with eAD on the CDT using 2 different scales and correlated the findings with neuropsychological testing and magnetic resonance imaging. The total CDT scores did not discriminate bvFTD and eAD; however, specific analysis of executive hand placement items successfully distinguished the groups, with eAD exhibiting greater errors than bvFTD. The performance on those executive hand placement items correlated with measures of naming as well as visuospatial and executive function. On tensor-based morphometry of the magnetic resonance images, executive hand placement correlated with right frontal volume. These findings suggest that lower performance on executive hand placement items occurs with involvement of the right dorsolateral frontal-parietal network for executive control in eAD, a network disproportionately affected in AD of early onset. Rather than the total performance on the clock task, the analysis of specific errors, such as executive hand placement, may be useful for early differentiation of eAD, bvFTD, and other conditions.

  17. Enhancement of carer skills and patient function in the non-pharmacological management of frontotemporal dementia (FTD: A call for randomised controlled studies

    Directory of Open Access Journals (Sweden)

    Claire M. O'Connor

    Full Text Available ABSTRACT FTD is a unique condition which manifests with a range of behavioural symptoms, marked dysfunction in activities of daily living (ADL and increased levels of carer burden as compared to carers of other dementias. No efficacious pharmacological interventions to treat FTD currently exist, and research on pharmacological symptom management is variable. The few studies on non-pharmacological interventions in FTD focus on either the carer or the patients' symptoms, and lack methodological rigour. This paper reviews and discusses current studies utilising non-pharmacological approaches, exposing the clear need for more rigorous methodologies to be applied in this field. Finally, a successful randomised controlled trial helped reduce behaviours of concern in dementia, and through implementing participation in tailored activities, the FTD-specific Tailored Activities Program (TAP is presented. Crucially, this protocol has scope to target both the person with FTD and their carer. This paper highlights that studies in this area would help to elucidate the potential for using activities to reduce characteristic behaviours in FTD, improving quality of life and the caregiving experience in FTD.

  18. Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology

    DEFF Research Database (Denmark)

    Clayton, Emma L.; Mizielinska, Sarah; Edgar, James R.;

    2015-01-01

    Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The a...

  19. Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology

    DEFF Research Database (Denmark)

    Clayton, Emma L.; Mizielinska, Sarah; Edgar, James R.

    2015-01-01

    Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The a...

  20. TDP-43 pathology in familial frontotemporal dementia and motor neuron disease without Progranulin mutations

    NARCIS (Netherlands)

    H. Seelaar (Harro); H. Jurgen Schelhaas; A. Azmani (Asma); B. Küsters (Benno); S.M. Rosso (Sonia); D.F. Majoor-Krakauer (Danielle); M.C. de Rijik (Maarten); P. Rizzu (Patrizia); M. ten Brummelhuis (Ming); P.A. van Doorn (Pieter); W. Kamphorst (Wouter); R. Willemsen (Rob); J.C. van Swieten

    2007-01-01

    textabstractFrontotemporal dementia is accompanied by motor neuron disease (FTD + MND) in ∼10% of cases. There is accumulating evidence for a clinicopathological overlap between FTD and MND based on observations of familial aggregation and neuropathological findings of ubiquitin-positive neuronal cy

  1. Frontotemporal dementia and its subtypes: A genome-wide association study

    NARCIS (Netherlands)

    R. Ferrari (Roberto); D.G. Hernandez (Dena); M.A. Nalls (Michael); J.D. Rohrer (Jonathan Daniel); A. Ramasamy (Adaikalavan); J.B.J. Kwok (John); C. Dobson-Stone (Carol); Brooks Brooks William S. (W.S.); C.J. Schofield (Christopher); G.M. Halliday (Glenda Margaret); J. Hodges (John); O. Piguet (Olivier); L. Bartley (Lauren); E. Thompson (Elizabeth); E. Haan (Eric); I. Hernández (Isabel); A. Ruiz (Agustin); M. Boada (Mercè); B. Borroni (Barbara); A. Padovani (Alessandro); C. Cruchaga (Carlos); N.J. Cairns (Nigel); L. Benussi (Luisa); G. Binetti (Giuliano); R. Ghidoni (Roberta); G. Forloni (Gianluigi); D. Galimberti (Daniela); C. Fenoglio (Chiara); M. Serpente (Maria); E. Scarpini (Elio); J. Clarimon (Jordi); A. Lleo (Alberto); R. Blesa (Rafael); M.L. Waldö (Maria Landqvist); K. Nilsson (Karin); C. Nilsson (Christer); I.R.A. Mackenzie (Ian); G.Y.R. Hsiung (Ging-Yuek); D.M.A. Mann (David); J. Grafman (Jordan); C.M. Morris (Chris); J. Attems (Johannes); T.D. Griffiths (Timothy); I.G. McKeith (Ian); A.W. Thomas (Alan); P. Pietrini (P.); E.D. Huey (Edward); E.M. Wassermann (Eric); A. Baborie (Atik); J.A.J. Jaros (Julian); M.C. Tierney (Michael); P. Pastor (Pau); C. Razquin (Cristina); S. Ortega-Cubero (Sara); E. Alonso (Elena); R. Perneczky (Robert); J. Diehl-Schmid (Janine); E.C. Alexopoulos (Evangelos); A. Kurz; I. Rainero (Innocenzo); M. Rubino (Maurizio); L. Pinessi (Lorenzo); E. Rogaeva (Ekaterina); P.H. St George-Hyslop (Peter); G. de Rossi (Giulio); F. Tagliavini (Fabrizio); G. Giaccone (Giuseppe); J.B. Rowe (James); J.C.M. Schlachetzki (Johannes C.); J. Uphill (James); J. Collinge (John); S. Mead (Simon); A. Danek (Adrian); V.M. Deerlin (Vivianna); M. Grossman (Murray); J.Q. Trojanowski (John); J. van der Zee (Jill); J. Deschamps (Jacqueline); T. van Langenhove (Tim); M. Cruts (Marc); C. van Broeckhoven (Christine); S.F. Cappa (Stefano); I. Le Ber (Isabelle); D. Hannequin (Didier); V. Golfier (Véronique); M. Vercelletto (Martine); A. Brice; B. Nacmias (Benedetta); S. Sorbi (Sandro); S. Bagnoli (Silvia); I. Piaceri (Irene); J.E. Nielsen (Jorgen); L.E. Hjermind (Lena); M. Riemenschneider (Matthias); M. Mayhaus (Manuel); B. Ibach (Bernd); G. Gasparoni (Gilles); I. Pichler (Irene); W. Gu (Wei); M. Rossor (Martin); N.C. Fox (Nick); J.D. Warren (Jason); M.G. Spillantini; H. Morris (Huw); P. Rizzu (Patrizia); P. Heutink (Peter); J. Snowden (Julie); S. Rollinson (Sara); A. Richardson (Anna); A. Gerhard (Alex); A.C. Bruni (Amalia); R. Maletta (Raffaele); F. Frangipane (Francesca); C. Cupidi (Chiara); L. Bernardi (Livia); M. Anfossi (Maria); V. Gallo (Valentina); A. Conidi (Andrea); N. Smirne (Nicoletta); S. Rademakers (Suzanne); M.C. Baker (Matthew); D.W. Dickson (Dennis); N.R. Graff-Radford (Neill); R.C. Petersen (Ronald); D.S. Knopman (David); K.A. Josephs (Keith); B.F. Boeve (Bradley); J.E. Parisi (Joseph); W. Seeley (William); B.L. Miller (Bruce Lars); A. Karydas (Anna); H. Rosen (Howard); J.C. van Swieten (John); E.G.P. Dopper (Elise); H. Seelaar (Harro); Y. Pijnenburg (Yolande); P. Scheltens (Philip); G. Logroscino (Giancarlo); R. Capozzo (Rosa); V. Novelli (Valeria); A.A. Puca (Annibale); C. Franceschi (Claudio); A. Postiglione (Alfredo); D.J. Milan (David); D. Sorrentino (Dario); M. Kristiansen (Mark); Y.T. Chiang; M.J. Graff (Maud J.L.); F. Pasquier (Florence); P.E. Rollin (Pierre); V. Deramecourt (Vincent); F. Lebert (Florence); D. Kapogiannis (Dimitrios); L. Ferrucci (Luigi); S. Pickering-Brown (Stuart); A. Singleton (Andrew); J. Hardy (John); M. Momeni (Mona)

    2014-01-01

    textabstractBackground: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify n

  2. Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech

    Science.gov (United States)

    Poole, Matthew L.; Brodtmann, Amy; Darby, David; Vogel, Adam P.

    2017-01-01

    Purpose: Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Method: Speech and…

  3. Diagnostic accuracy of consensus diagnostic criteria for frontotemporal dementia in a memory clinic population

    NARCIS (Netherlands)

    Y. Pijnenburg (Yolande); J.L. Mulder (Jacqueline); J.C. van Swieten (John); B.M. Uitdehaag (Bernard); M. Stevens (Martijn); P. Scheltens (Philip); C. Jonker (Cees)

    2008-01-01

    textabstractBackground/Aims: The goal of the present study was to evaluate the diagnostic accuracy of the core diagnostic criteria for frontotemporal dementia (FTD) [Neary D, et al: Neurology 1998;51:1546-1554] within a memory clinic population. Methods: The 5 core diagnostic criteria for FTD were o

  4. The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia, Lewy body dementia, and Alzheimer's disease: clinical experience in China.

    Science.gov (United States)

    Liu, Shuling; Jin, Yi; Shi, Zhihong; Huo, Ya Ruth; Guan, Yalin; Liu, Mengyuan; Liu, Shuai; Ji, Yong

    2017-06-01

    Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia. A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI). FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients. BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.

  5. Dissociation in Rating Negative Facial Emotions between Behavioral Variant Frontotemporal Dementia and Major Depressive Disorder.

    Science.gov (United States)

    Chiu, Isabelle; Piguet, Olivier; Diehl-Schmid, Janine; Riedl, Lina; Beck, Johannes; Leyhe, Thomas; Holsboer-Trachsler, Edith; Berres, Manfred; Monsch, Andreas U; Sollberger, Marc

    2016-11-01

    Features of behavioral variant frontotemporal dementia (bvFTD) such as executive dysfunction, apathy, and impaired empathic abilities are also observed in major depressive disorder (MDD). This may contribute to the reason why early stage bvFTD is often misdiagnosed as MDD. New assessment tools are thus needed to improve early diagnosis of bvFTD. Although emotion processing is affected in bvFTD and MDD, growing evidence indicates that the pattern of emotion processing deficits varies between the two disorders. As such, emotion processing paradigms have substantial potentials to distinguish bvFTD from MDD. The current study compared 25 patients with bvFTD, 21 patients with MDD, 21 patients with Alzheimer disease (AD) dementia, and 31 healthy participants on a novel facial emotion intensity rating task. Stimuli comprised morphed faces from the Ekman and Friesen stimulus set containing faces of each sex with two different degrees of emotion intensity for each of the six basic emotions. Analyses of covariance uncovered a significant dissociation between bvFTD and MDD patients in rating the intensity of negative emotions overall (i.e., bvFTD patients underrated negative emotions overall, whereas MDD patients overrated negative emotions overall compared with healthy participants). In contrast, AD dementia patients rated negative emotions similarly to healthy participants, suggesting no impact of cognitive deficits on rating facial emotions. By strongly differentiating bvFTD and MDDpatients through negative facial emotions, this sensitive and short rating task might help improve the early diagnosis of bvFTD. Copyright © 2016 American Association for Geriatric Psychiatry. All rights reserved.

  6. Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17

    Directory of Open Access Journals (Sweden)

    Nitrini Ricardo

    2001-01-01

    Full Text Available OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17. BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD, the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 ± 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.

  7. Using the Disease State Fingerprint Tool for Differential Diagnosis of Frontotemporal Dementia and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Muñoz-Ruiz

    2016-07-01

    Full Text Available Background: Disease State Index (DSI and its visualization, Disease State Fingerprint (DSF, form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. Aims: To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD and Alzheimer's disease (AD. Methods: The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases. We utilized data from neuropsychological tests, volumetric magnetic resonance imaging, single-photon emission tomography, cerebrospinal fluid biomarkers and the APOE genotype. The DSI classification results were calculated with a combination of leave-one-out cross-validation and bootstrapping. A DSF visualization of a FTD patient is presented as an example. Results: The DSI distinguishes controls from FTD (area under the receiver-operator curve, AUC = 0.99 and AD (AUC = 1.00 very well and achieves a good differential diagnosis between AD and FTD (AUC = 0.89. In subsamples of autopsy-confirmed cases (AUC = 0.97 and clinically diagnosed cases (AUC = 0.94, differential diagnosis of AD and FTD performs very well. Conclusions: DSI is a promising computer-assisted biomarker approach for aiding in the diagnostic process of dementing diseases. Here, DSI separates controls from dementia and differentiates between AD and FTD.

  8. Using the Disease State Fingerprint Tool for Differential Diagnosis of Frontotemporal Dementia and Alzheimer's Disease

    Science.gov (United States)

    Muñoz-Ruiz, Miguel Ángel; Hall, Anette; Mattila, Jussi; Koikkalainen, Juha; Herukka, Sanna-Kaisa; Husso, Minna; Hänninen, Tuomo; Vanninen, Ritva; Liu, Yawu; Hallikainen, Merja; Lötjönen, Jyrki; Remes, Anne M.; Alafuzoff, Irina; Soininen, Hilkka; Hartikainen, Päivi

    2016-01-01

    Background Disease State Index (DSI) and its visualization, Disease State Fingerprint (DSF), form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. Aims To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and Alzheimer's disease (AD). Methods The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases. We utilized data from neuropsychological tests, volumetric magnetic resonance imaging, single-photon emission tomography, cerebrospinal fluid biomarkers and the APOE genotype. The DSI classification results were calculated with a combination of leave-one-out cross-validation and bootstrapping. A DSF visualization of a FTD patient is presented as an example. Results The DSI distinguishes controls from FTD (area under the receiver-operator curve, AUC = 0.99) and AD (AUC = 1.00) very well and achieves a good differential diagnosis between AD and FTD (AUC = 0.89). In subsamples of autopsy-confirmed cases (AUC = 0.97) and clinically diagnosed cases (AUC = 0.94), differential diagnosis of AD and FTD performs very well. Conclusions DSI is a promising computer-assisted biomarker approach for aiding in the diagnostic process of dementing diseases. Here, DSI separates controls from dementia and differentiates between AD and FTD. PMID:27703465

  9. Reconocimiento facial de emociones básicas y complejas en una población de pacientes con demencia frontotemporal variante frontal Facial recognition of basic and complex emotions in a population of patients with frontal variant of frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    María Eugenia Tabernero

    2011-12-01

    Full Text Available La variante frontal de la Demencia Frontotemporal (DFTvf se caracteriza por un severo trastorno de la conducta y la personalidad, explicado por alteraciones en el procesamiento emocional y/o en la Teoría de la Mente (TdM. Objetivo: Evaluar los procesos cognitivos involucrados en a resolución del Test de Caras (Baron-Cohen et al., 1997 en comparación con el test Lectura de la Mente en los Ojos (LMO (Baron-Cohen et al., 2001 y la utilidad de ambos para el diagnóstico de alteraciones en la TdM en pacientes con DFTvf. Población: 20 pacientes con diagnóstico de DFTvf, media de edad 66,9 años y escolaridad 6,25 años. Resultados: Correlación significativa entre LMO y el Test de Caras. Doble disociación entre ambas pruebas. Conclusión: La presencia de correlaciones indica que ambas pruebas se afectan en esta demencia, resultando herramientas de igual valor clínico. El hallazgo de disociaciones indica que cada una de ellas evalúa procesos cognitivos parcialmente independientesThe frontal variant of frontotemporal dementia (FTDfv is characterized by a severe behavioural and personality impairment, explained by alterations in the emotional process and/or in Theory of Mind (ToM. Objective: To assess the cognitive processes involved in performing the Faces Test (Baron-Cohen et al., 1997 in comparison with Reading de Mind in the Eyes Test (RME (Baron-Cohen et al., 2001, and the utility of both in the diagnosis of ToM alterations in FTDfv patients. Subjects: 20 patients diagnosed with FTDfv, mean age 66,9 years and mean education 6,25 years. Results: Significative correlation between RME and Faces Test. Double dissociation between these tests. Conclusion: The presence of correlations indicates that both tests are affected in this dementia, being both useful as clinical tools. The dissociations founded indicates that each one assesses partially-independent cognitive processes.

  10. Factors Underpinning Caregiver Burden in Frontotemporal Dementia Differ in Spouses and their Children

    Science.gov (United States)

    Kaizik, Cassandra; Caga, Jashelle; Camino, Julieta; O’Connor, Claire M.; McKinnon, Colleen; Oyebode, Jan R.; Piguet, Olivier; Hodges, John R.; Mioshi, Eneida

    2017-01-01

    The objectives of this observational study were to (1) compare spousal and child caregiver burden; (2) compare co-resident and live-out child caregiver burden; and (3) investigate factors influencing spousal and child caregiver burden. Data was collected from 90 caregivers of people with frontotemporal degeneration (FTD) recruited from the Frontotemporal Dementia Research Group (Frontier) at Neuroscience Research, Australia. Of this caregiver group, 43 were spousal caregivers and 47 were child caregivers. Caregiver burden and emotional state were evaluated using the short Zarit Burden Interview and the short version of the Depression, Anxiety and Stress Scale-21. The Social Network Index was applied to ascertain the social network of the caregiver, while the Intimate Bond Measure was used to evaluate the current quality of the relationship between the caregiver and the person with dementia. The Frontotemporal Dementia Rating Scale was used to assess severity of dementia. Spousal and child caregivers experienced similar levels of burden, depression, anxiety, and stress, regardless of disease severity. Co-resident child caregivers had smaller social networks and greater burden than live-out caregivers. Dementia severity was key in spousal caregiver burden, whereas caregiver depression was most important in child caregiver burden. Child and spousal caregivers of individuals with FTD share similar levels of burden, influenced by different factors. Future interventions need to account for these differences. PMID:28106550

  11. Factors Underpinning Caregiver Burden in Frontotemporal Dementia Differ in Spouses and their Children.

    Science.gov (United States)

    Kaizik, Cassandra; Caga, Jashelle; Camino, Julieta; O'Connor, Claire M; McKinnon, Colleen; Oyebode, Jan R; Piguet, Olivier; Hodges, John R; Mioshi, Eneida

    2017-01-01

    The objectives of this observational study were to (1) compare spousal and child caregiver burden; (2) compare co-resident and live-out child caregiver burden; and (3) investigate factors influencing spousal and child caregiver burden. Data was collected from 90 caregivers of people with frontotemporal degeneration (FTD) recruited from the Frontotemporal Dementia Research Group (Frontier) at Neuroscience Research, Australia. Of this caregiver group, 43 were spousal caregivers and 47 were child caregivers. Caregiver burden and emotional state were evaluated using the short Zarit Burden Interview and the short version of the Depression, Anxiety and Stress Scale-21. The Social Network Index was applied to ascertain the social network of the caregiver, while the Intimate Bond Measure was used to evaluate the current quality of the relationship between the caregiver and the person with dementia. The Frontotemporal Dementia Rating Scale was used to assess severity of dementia. Spousal and child caregivers experienced similar levels of burden, depression, anxiety, and stress, regardless of disease severity. Co-resident child caregivers had smaller social networks and greater burden than live-out caregivers. Dementia severity was key in spousal caregiver burden, whereas caregiver depression was most important in child caregiver burden. Child and spousal caregivers of individuals with FTD share similar levels of burden, influenced by different factors. Future interventions need to account for these differences.

  12. The Differences in level and rhythm of locomotor activity between patients with Alzheimer disease and those with frontotemporal dementia%阿尔茨海默病和额颞叶痴呆徘徊行为的比较

    Institute of Scientific and Technical Information of China (English)

    廖晓艳; 牧本清子; 山川みやえ; 何湘军; 李亦蕾

    2011-01-01

    Objective To delineate the differences in level and thythm of locomotor activity between wanderers with Alzheimer's disease (AD) and those with frontotemporal dementia (FTD). Methods The study was conducted in a dementia care unit at a hospital in Osaka , Japan from September 2008 to September 2009. Twenty-four-hour movements of 27 ambulatory AD inpatients and 7 FTD inpatients were coded consecutively by the IC tag monitoring system. Results There were no significant differences in the distribution of sex , duration of dementia, clinical dementia rating (CDR)and mini-mental state examination (MMSE) scores between two dementia types. However, patients with FTD were much younger than those with AD [(63.43 ± 14.93) yr vs (73.89 ± 9.12) yr, ρ< 0.05] and age of onset were significantly different between two dementia types [ (58.17 ± 15.16) yr vs (70.16 ± 9.26) yr,ρ<0.05]. There were increased distances moved during 6:00 ~23 :59 in FTD group comparing with AD group [ (4842.44 ± 2617.94)m vs (2119.39 ±2535.59)m,ρ<0.05 ] whereas difference in activity level during 0 : 00 ~5 :59 were not signif'icant between two groups.Meanwhile , non-parametric analyses revealed that FTD patients had a more stable and consolidate thythm of day to day ambulation circles [(0.50 ± 0.11) vs (0.29 ± 0.15), ρ<0.01] and less intra-daily activity fragmentation [(2.80 ±0.74) vs (4.07 ± 0.95) ,ρ< 0.01] compared with AD group. Conclusions Patients with AD and those with FTD have dif'ferent patterns of wandering behaviour, suggesting that it is necessary to develop subtype-specific non-pharmaceutical strategies for wandering behavior in dementia patients.%目的 比较阿尔茨海默病和额颞叶痴呆徘徊者步行活动水平及活动节律的差异.方法 利用电子示踪监测系统对阿尔茨海默病(Alzheimer disease,AD)徘徊者27例及额颞叶痴呆(frontotemporal dementia,FTD)徘徊者7例进行连续30 d的24 h活动监测,比较两组日、夜活动水

  13. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Cho, S. S.; Jeong, J.; Kang, S. J.; Na, D. L.; Choe, Y. S.; Lee, K. H.; Choi, Y.; Kim, B. T.; Kim, S. E. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD.

  14. Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Chow TW

    2011-07-01

    Full Text Available Tiffany W Chow1–6, Ariel Graff-Guerrero4,6, Nicolaas PLG Verhoeff2–4,7, Malcolm A Binns3,8, David F Tang-Wai5,9, Morris Freedman1,3,5, Mario Masellis5,10, Sandra E Black3,5,10, Alan A Wilson4,6, Sylvain Houle4,6, Bruce G Pollock4,61Division of Neurology, 2Department of Psychiatry, 3Rotman Research Institute, Baycrest; 4Departments of Psychiatry, 5Medicine, Division of Neurology, University of Toronto; 6Centre for Addiction and Mental Health PET Centre; 7Kunin-Lunenfeld Applied Research Unit, Baycrest; 8Dalla Lana School of Public Health, University of Toronto; 9University Health Network Memory Clinic; 10LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaBackground: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD, and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.Methods: Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7–8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.Results: Voxel-wise parametric image analysis of positron emission tomography (PET data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [18F]-fluorodeoxyglucose (FDG normalized

  15. Brain Serotonergic and Noradrenergic Deficiencies in Behavioral Variant Frontotemporal Dementia Compared to Early-Onset Alzheimer's Disease

    NARCIS (Netherlands)

    Vermeiren, Yannick; Janssens, Jana; Aerts, Tony; Martin, Jean-Jacques; Sieben, Anne; Van Dam, Debby; De Deyn, Peter P.

    2016-01-01

    Routinely prescribed psychoactive drugs in behavioral variant frontotemporal dementia (FTD) for improvement of (non) cognitive symptoms are primarily based on monoamine replacement or augmentation strategies. These were, however, initially intended to symptomatically treat other degenerative, behavi

  16. Brain Serotonergic and Noradrenergic Deficiencies in Behavioral Variant Frontotemporal Dementia Compared to Early-Onset Alzheimer's Disease

    NARCIS (Netherlands)

    Vermeiren, Yannick; Janssens, Jana; Aerts, Tony; Martin, Jean-Jacques; Sieben, Anne; Van Dam, Debby; De Deyn, Peter P.

    2016-01-01

    Routinely prescribed psychoactive drugs in behavioral variant frontotemporal dementia (FTD) for improvement of (non) cognitive symptoms are primarily based on monoamine replacement or augmentation strategies. These were, however, initially intended to symptomatically treat other degenerative,

  17. Familial frontotemporal dementia with ubiquitin-positive inclusions is linked to chromosome 17q21-22

    NARCIS (Netherlands)

    S.M. Rosso (Sonia); W. Kamphorst (Wouter); B.M. de Graaf (Bianca); R. Willemsen (Rob); R. Ravid (Rivka); M.F. Niermeijer (Martinus); M.G. Spillantini; P. Heutink (Peter)

    2001-01-01

    textabstractHereditary frontotemporal dementia (FTD) is an autosomal dominant neurodegenerative disorder that is associated with mutations in the tau gene and with the pathological accumulation of hyperphosphorylated tau protein in affected brain cells in about a quarter of cases.

  18. The neural correlates and clinical characteristics of psychosis in the frontotemporal dementia continuum and the C9orf72 expansion

    Directory of Open Access Journals (Sweden)

    Emma M Devenney

    2017-01-01

    Conclusions: This study underlines the need to consider and assess for psychotic symptoms in the frontotemporal dementia-amyotrophic lateral sclerosis continuum particularly in those with C9orf72 gene expansions. The network of brain regions identified in this study is strikingly similar to that identified in other psychotic disorders such as schizophrenia, which suggests that treatment strategies in psychiatry may be beneficial for the management of psychotic symptoms in frontotemporal dementia.

  19. Neuropsychological, behavioral, and anatomical evolution in right temporal variant frontotemporal dementia: a longitudinal and post-mortem single case analysis.

    Science.gov (United States)

    Henry, Maya L; Wilson, Stephen M; Ogar, Jennifer M; Sidhu, Manu S; Rankin, Katherine P; Cattaruzza, Tatiana; Miller, Bruce L; Gorno-Tempini, Maria Luisa; Seeley, William W

    2014-01-01

    We describe a patient with semantic variant of frontotemporal dementia who received longitudinal clinical evaluations and structural MRI scans and subsequently came to autopsy. She presented with early behavior changes and semantic loss for foods and people and ultimately developed a pervasive semantic impairment affecting social-emotional as well as linguistic domains. Imaging revealed predominant atrophy of the right temporal lobe, with later involvement of the left, and pathology confirmed bilateral temporal involvement. Findings support the view that left and right anterior temporal lobes serve as semantic hubs that may be affected differentially in semantic variant by early, relatively unilateral damage.

  20. Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior.

    Science.gov (United States)

    Viskontas, Indre V; Possin, Katherine L; Miller, Bruce L

    2007-12-01

    Recent investigations into the brain substrates of behavioral changes in frontotemporal dementia (FTD) demonstrate that the orbitofrontal cortex (OFC) plays a crucial role in normal social and emotional behavior. The initial symptoms of FTD reflect the early involvement of OFC as well as the disruption of an associated network involving the insula, striatum, and medial frontal lobes. As predicted by patients with other types of OFC lesions, FTD patients show impairments involving stimulus-reward reversal learning, response inhibition, and ability to judge the appropriateness of their behavior in the social context. While the natural reward system remains intact in these patients, that is, patients will seek out directly rewarding stimuli, such as food and sex, with progressive OFC dysfunction they lose the ability to process complex stimulus-reward contingencies. These abnormalities are apparent in their social interactions, which break down early in the disease. Also, deficits in emotion recognition and empathy have been directly linked to OFC atrophy in these patients. In contrast, some patients with early FTD show intact cognitive skills, including memory and executive functioning. Here, we review the behavioral and neuropsychological changes that accompany OFC atrophy in FTD and argue that phylogenetically new neurons found in this region, called von Economo neurons, are selectively vulnerable in FTD.

  1. Frontotemporal dementia and language networks: cortical thickness reduction is driven by dyslexia susceptibility genes

    Science.gov (United States)

    Paternicó, Donata; Manes, Marta; Premi, Enrico; Cosseddu, Maura; Gazzina, Stefano; Alberici, Antonella; Archetti, Silvana; Bonomi, Elisa; Cotelli, Maria Sofia; Cotelli, Maria; Turla, Marinella; Micheli, Anna; Gasparotti, Roberto; Padovani, Alessandro; Borroni, Barbara

    2016-01-01

    Variations within genes associated with dyslexia result in a language network vulnerability, and in patients with Frontotemporal Dementia (FTD), language disturbances represent a disease core feature. Here we explored whether variations within three related-dyslexia genes, namely KIAA0319, DCDC2, and CNTNAP, might affect cortical thickness measures in FTD patients. 112 FTD patients underwent clinical and neuropsychological examination, genetic analyses and brain Magnetic Resonance Imaging (MRI). KIAA0319 rs17243157 G/A, DCDC2 rs793842 A/G and CNTNAP2 rs17236239 A/G genetic variations were assessed. Cortical thickness was analysed by Freesurfer. Patients carrying KIAA0319 A*(AG or AA) carriers showed greater cortical thickness atrophy in the left fusiform and inferior temporal gyri, compared to KIAA0319 GG (p ≤ 0.001). Patients carrying CNTNAP2 G*(GA or GG) showed reduced cortical thickness in the left insula thenCNTNAP2 AA carriers (p≤0.001). When patients with both at-risk polymorphisms were considered (KIAA0319 A* and CNTNAP2 G*), greater and addictive cortical thickness atrophy of the left insula and the inferior temporal gyrus was demonstrated (p ≤ 0.001). No significant effect of DCDC2 was found. In FTD, variations of KIAA0319 and CNTNAP2 genes were related to cortical thickness abnormalities in those brain areas involved in language abilities. These findings shed light on genetic predisposition in defining phenotypic variability in FTD. PMID:27484312

  2. White Matter Changes Associated with Resting Sympathetic Tone in Frontotemporal Dementia vs. Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Mario F Mendez

    Full Text Available Resting sympathetic tone, a measure of physiological arousal, is decreased in patients with apathy and inertia, such as those with behavioral variant frontotemporal dementia (bvFTD and other frontally-predominant disorders.To identify the neuroanatomical correlates of skin conductance levels (SCLs, an index of resting sympathetic tone and apathy, among patients with bvFTD, where SCLs is decreased, compared to those with Alzheimer's disease (AD, where it is not.This study analyzed bvFTD (n = 14 patients and a comparison group with early-onset AD (n = 19. We compared their resting SCLs with gray matter and white matter regions of interest and white matter measures of fiber integrity on magnetic resonance imaging and diffusion tensor imaging.As expected, bvFTD patients, compared to AD patients, had lower SCLs, which correlated with an apathy measure, and more gray matter loss and abnormalities of fiber integrity (fractional anisotropy and mean diffusivity in frontal-anterior temporal regions. After controlling for group membership, the SCLs were significantly correlated with white matter volumes in the cingulum and inferior parietal region in the right hemisphere.Among dementia patients, SCLs, and resting sympathetic tone, may correlate with quantity of white matter, rather than with gray matter or with white matter fiber integrity. Loss of white matter volumes, especially involving a right frontoparietal network, may reflect chronic loss of cortical axons that mediate frontal control of resting sympathetic tone, changes that could contribute to the apathy and inertia of bvFTD and related disorders.

  3. Etiology and pathophysiology of frontotemporal dementia, Parkinson disease and Alzheimer disease: lessons from genetic studies.

    Science.gov (United States)

    Wider, Christian; Wszolek, Zbigniew K

    2008-01-01

    Genetic studies have led to major discoveries in the pathogenesis of various neurodegenerative diseases. Ubiquitin-positive familial frontotemporal dementia was recently found to be caused by mutations in the progranulin gene (PGRN), and the major constituent of the inclusions, TDP-43, was subsequently identified. The tau gene (MAPT) causes frontotemporal dementia with parkinsonism linked to chromosome 17. In Parkinson disease, LRRK2 mutations have emerged as a major cause of both familial and sporadic forms, adding to the previously known genes SNCA,PRKN,DJ1 and PINK1. Several genes have been implicated in Alzheimer disease, including the APP gene and the PSEN genes. Recently, variants in the sortilin-related receptor 1 gene, SORL1, were associated with Alzheimer disease. 2008 S. Karger AG, Basel

  4. A Pilot Study on the effects of Music Therapy on Frontotemporal Dementia - developing a research protocol

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner; Wigram, Tony; Ottesen, Anne Marie

    2009-01-01

    Background: Some forms of dementia particularly affect the frontal parts of the brain which, in some cases, causes the onset of severe behavioural and psychological symptoms. No specific treatment for the primary diseases that cause these frontotemporal dementia conditions has yet been developed....... As an example of a non-pharmacologic treatment procedure music therapy was investigated. With the focus to develop a research protocol for a future larger population study a pilot study was carried out. In two case studies a combination of data collection methods were examined with the overall goal to document...... of Life (ADRQL), the Cohen-Mansfield Agitation Inventory (CMAI), and the Neuro-Psychiatric Inventory (NPI), and related to case descriptions and video analyses. Results: Recommendations for a mixed method research protocol focused on measuring the effect of music therapy with persons with frontotemporal...

  5. The role of social cognition in moral judgment in frontotemporal dementia.

    Science.gov (United States)

    Gleichgerrcht, Ezequiel; Torralva, Teresa; Roca, María; Pose, Máriangeles; Manes, Facundo

    2011-01-01

    Patients with behavioral variant frontotemporal dementia (bvFTD) exhibit a set of behavioral disturbances that have been strongly associated with involvement of the prefrontal cortex (PFC). Many such disturbances have been linked to impaired moral behavior, especially in regard to "personal" or "emotionally driven" moral dilemmatic judgment, which has been demonstrated to also depend on the integrity of the PFC. In this study, we administered a personal moral dilemma (the footbridge dilemma) and social cognition measures to patients with early bvFTD, who were also assessed with an extensive neuropsychological battery, including moral knowledge, cognitive and emotional empathy, and affective decision-making. BvFTD patients who would push a man off a footbridge (knowing this would kill him) to save the life of five workers who would have been otherwise killed by the train showed significantly lower scores on affective Theory of Mind (ToM) relative to those bvFTD patients who responded negatively. No significant differences were found on other sociodemographic, neuropsychological or social cognition variables. This study reveals that altered dilemmatic judgment may be related to impaired affective ToM, which has important clinical and theoretical implications. © 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

  6. NREM sleep transient events in fronto-temporal dementia: beyond sleep stage architecture.

    Science.gov (United States)

    Maestri, Michelangelo; Carnicelli, Luca; Economou, Nicholas-Tiberio; Bonakis, Anastasios; Paparrigopoulos, Thomas; Papageorgiou, Sokratis T; Giorgi, Filippo Sean; Di Coscio, Elisa; Tognoni, Gloria; Ferri, Raffaele; Bonuccelli, Ubaldo; Bonanni, Enrica

    2015-01-01

    Frontotemporal dementia (FTD) is increasingly becoming recognized as a major cause of early onset (sleep disorders significantly impair patients' and caregivers' quality of life in neurodegenerative diseases, polysomnographic data in FTD patients are scarce in literature. Aim of our study was to investigate sleep microstructure in FTD, by means of Cyclic Alternating Pattern (CAP), in a group of ten behavioral variant FTD patients (6 M, 4 F; mean age 61.2±7.3 years; disease duration: 1.4±0.7 years) and to compare them with cognitively intact healthy elderly. Sleep in FTD patients was altered at different levels, involving not only the conventional sleep stage architecture parameters (total sleep time, single stage percentage, NREM/REM cycle organization), but also microstructure. FTD subjects showed CAP disruption with decreased slow wave activity related phases (A1 index, n/h:14.5±6.8 vs 38.8±6.6; psleep variables and neuropsychological tests were found. Sleep impairment in FTD may be specifically related to the specific frontal lobe involvement in the neurodegenerative process. The pattern of alterations seems somewhat peculiar, probably due to the anatomical distribution of the neurodegenerative process with a major impact on frontal lobe generated sleep transients, and a substantial sparing of phenomena related to the posterior cortex.

  7. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

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    Sandra Almeida

    2012-10-01

    Full Text Available The pathogenic mechanisms of frontotemporal dementia (FTD remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X. In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by PGRN expression. Our findings identify cell-autonomous, reversible defects in patient neurons with PGRN deficiency, and provide a compelling model for studying PGRN-dependent pathogenic mechanisms and testing potential therapies.

  8. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

    Directory of Open Access Journals (Sweden)

    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  9. Emotion recognition in frontotemporal dementia and Alzheimer's disease: A new film-based assessment.

    Science.gov (United States)

    Goodkind, Madeleine S; Sturm, Virginia E; Ascher, Elizabeth A; Shdo, Suzanne M; Miller, Bruce L; Rankin, Katherine P; Levenson, Robert W

    2015-08-01

    Deficits in recognizing others' emotions are reported in many psychiatric and neurological disorders, including autism, schizophrenia, behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Most previous emotion recognition studies have required participants to identify emotional expressions in photographs. This type of assessment differs from real-world emotion recognition in important ways: Images are static rather than dynamic, include only 1 modality of emotional information (i.e., visual information), and are presented absent a social context. Additionally, existing emotion recognition batteries typically include multiple negative emotions, but only 1 positive emotion (i.e., happiness) and no self-conscious emotions (e.g., embarrassment). We present initial results using a new task for assessing emotion recognition that was developed to address these limitations. In this task, respondents view a series of short film clips and are asked to identify the main characters' emotions. The task assesses multiple negative, positive, and self-conscious emotions based on information that is multimodal, dynamic, and socially embedded. We evaluate this approach in a sample of patients with bvFTD, AD, and normal controls. Results indicate that patients with bvFTD have emotion recognition deficits in all 3 categories of emotion compared to the other groups. These deficits were especially pronounced for negative and self-conscious emotions. Emotion recognition in this sample of patients with AD was indistinguishable from controls. These findings underscore the utility of this approach to assessing emotion recognition and suggest that previous findings that recognition of positive emotion was preserved in dementia patients may have resulted from the limited sampling of positive emotion in traditional tests.

  10. Emotion Recognition in Frontotemporal Dementia and Alzheimer's Disease: A New Film-Based Assessment

    Science.gov (United States)

    Goodkind, Madeleine S.; Sturm, Virginia E.; Ascher, Elizabeth A.; Shdo, Suzanne M.; Miller, Bruce L.; Rankin, Katherine P.; Levenson, Robert W.

    2015-01-01

    Deficits in recognizing others' emotions are reported in many psychiatric and neurological disorders, including autism, schizophrenia, behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Most previous emotion recognition studies have required participants to identify emotional expressions in photographs. This type of assessment differs from real-world emotion recognition in important ways: Images are static rather than dynamic, include only 1 modality of emotional information (i.e., visual information), and are presented absent a social context. Additionally, existing emotion recognition batteries typically include multiple negative emotions, but only 1 positive emotion (i.e., happiness) and no self-conscious emotions (e.g., embarrassment). We present initial results using a new task for assessing emotion recognition that was developed to address these limitations. In this task, respondents view a series of short film clips and are asked to identify the main characters' emotions. The task assesses multiple negative, positive, and self-conscious emotions based on information that is multimodal, dynamic, and socially embedded. We evaluate this approach in a sample of patients with bvFTD, AD, and normal controls. Results indicate that patients with bvFTD have emotion recognition deficits in all 3 categories of emotion compared to the other groups. These deficits were especially pronounced for negative and self-conscious emotions. Emotion recognition in this sample of patients with AD was indistinguishable from controls. These findings underscore the utility of this approach to assessing emotion recognition and suggest that previous findings that recognition of positive emotion was preserved in dementia patients may have resulted from the limited sampling of positive emotion in traditional tests. PMID:26010574

  11. One size does not fit all: face emotion processing impairments in semantic dementia, behavioural-variant frontotemporal dementia and Alzheimer's disease are mediated by distinct cognitive deficits.

    Science.gov (United States)

    Miller, Laurie A; Hsieh, Sharpley; Lah, Suncica; Savage, Sharon; Hodges, John R; Piguet, Olivier

    2012-01-01

    Patients with frontotemporal dementia (both behavioural variant [bvFTD] and semantic dementia [SD]) as well as those with Alzheimer's disease (AD) show deficits on tests of face emotion processing, yet the mechanisms underlying these deficits have rarely been explored. We compared groups of patients with bvFTD (n = 17), SD (n = 12) or AD (n = 20) to an age- and education-matched group of healthy control subjects (n = 36) on three face emotion processing tasks (Ekman 60, Emotion Matching and Emotion Selection) and found that all three patient groups were similarly impaired. Analyses of covariance employed to partial out the influences of language and perceptual impairments, which frequently co-occur in these patients, provided evidence of different underlying cognitive mechanisms. These analyses revealed that language impairments explained the original poor scores obtained by the SD patients on the Ekman 60 and Emotion Selection tasks, which involve verbal labels. Perceptual deficits contributed to Emotion Matching performance in the bvFTD and AD patients. Importantly, all groups remained impaired on one task or more following these analyses, denoting a primary emotion processing disturbance in these dementia syndromes. These findings highlight the multifactorial nature of emotion processing deficits in patients with dementia.

  12. Tau protein in frontotemporal dementia linked to chromosome 3 (FTD-3).

    Science.gov (United States)

    Yancopoulou, Despina; Crowther, R Anthony; Chakrabarti, Lisa; Gydesen, Susanne; Brown, Jeremy M; Spillantini, Maria Grazia

    2003-08-01

    Recent work on frontotemporal dementia (FTD) has revealed the existence of at least 3 genetically distinct groups of inherited FTD: FTDP-17, FTD and motor neuron disease linked to chromosome 9, and FTD linked to chromosome 3 (FTD-3). Tau, on chromosome 17, is the only gene where mutations have been identified and its involvement in FTD has been firmly established. The genes on chromosome 9 and chromosome 3 associated with familial forms of FTD remain to be identified. Abnormal aggregates of tau protein characterize the brain lesions of FTDP-17 patients and ubiquitin inclusions have been found in FTD with motor neuron disease linked to chromosome 9. In this study the frontal cortices of 3 FTD-3 patients from a unique Danish family were examined for characteristic neuropathological features. In these brains tau inclusions were present in neurons and some glial cells in the absence of beta-amyloid deposits. The presence of filamentous tau protein in the frontal cortex of these patients suggests a possible link between tau and the genetic defect present on chromosome 3 and associated with FTD-3, although the limited amount of tau deposits observed makes it difficult to define this as a tauopathy.

  13. Amnesia in frontotemporal dementia: shedding light on the Geneva historical data.

    Science.gov (United States)

    Papageorgiou, Sokratis G; Beratis, Ion N; Horvath, Judit; Herrmann, François R; Bouras, Constantin; Kövari, Enikö

    2016-04-01

    Recent accumulated evidence indicates that episodic memory impairments could be part of the initial clinical expression of frontotemporal dementia (FTD). An early study on this issue was carried out by Constantinidis and colleagues in 1974, but it was subsequently overlooked for a long period of time. The scope of the present research was: (a) to explore the presence of early episodic memory impairments in the entire population of neuropathologically confirmed FTD patients from the Geneva brain collection; and (b) to expand the present insight on the association between the initial symptomatology and various characteristics, namely gender, age at onset, disease duration, and presence of Pick body neuropathology. A careful review of the records of 50 FTD patients hospitalized at the Department of Psychiatry of the Bel-Air Hospital, Geneva, Switzerland, from 1929 to 1999, was conducted. Further in-depth neuropathological analysis with novel immunohistological methods was carried out in 37 of the cases. The data showed that memory impairments were the first clinical symptom in several of the patients. In addition, this specific phenotypic expression of FTD was associated with the female gender, advanced age, and positive Pick body neuropathology. The current findings give the opportunity to historically vindicate the early work of Constantinidis and colleagues. In addition, the novel observations about the association of episodic memory impairments with the female gender and positive Pick body neuropathology add to the existing knowledge about this phenotypic expression of FTD.

  14. Apraxia profile differentiates behavioural variant frontotemporal from Alzheimer's dementia in mild disease stages.

    Science.gov (United States)

    Johnen, Andreas; Tokaj, Amelie; Kirschner, Anne; Wiendl, Heinz; Lueg, Gero; Duning, Thomas; Lohmann, Hubertus

    2015-07-01

    Despite refined criteria for behavioural variant frontotemporal dementia (bvFTD), its differentiation from Alzheimer's dementia (AD) remains difficult at early clinical presentation. Apraxia is not considered as a supportive feature for the diagnosis of bvFTD, but for AD. However, only few studies have quantified praxis disturbances in mild disease stages and their specificity for AD compared with bvFTD remains indistinct. We explore apraxia in bvFTD and investigate the differential validity of apraxia screening tests to distinguish between AD, bvFTD and healthy controls (HC). We compared composite apraxia scores assessed with standardised neuropsychological screening tests as well as performance in praxis subdomains in patients who fulfil current clinical criteria for AD (N=20), bvFTD (N=20), and in HC (N=20). Composite scores of apraxia screening tests provided high diagnostic accuracy for detecting mild stages of both neurodegenerative disorders compared with HC (sensitivity: 75-95%; specificity: 70-90%). Both patient groups showed pronounced impairments in limb praxis, especially in imitation of hand and finger postures (bvFTD: 71.7%; AD: 55.5%; HC: 86.7%) and pantomime of object use (bvFTD: 88.6%; AD: 81.4%; HC: 97.5%). Beyond that, patients with bvFTD displayed a unique profile of deficits for imitating face postures (bvFTD: 69%; AD: 88%; HC: 95.5%). Praxis disturbances are important but under-represented diagnostic features in mild stages of AD and bvFTD. Apraxia screening tests are easily applicable diagnostic tools, which may support clinical diagnoses of both neurodegenerative diseases. The analysis of individual apraxia profiles can effectively facilitate differential diagnosis of AD and bvFTD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Methylphenidate ('Ritalin') can ameliorate abnormal risk-taking behavior in the frontal variant of frontotemporal dementia.

    Science.gov (United States)

    Rahman, Shibley; Robbins, Trevor W; Hodges, John R; Mehta, Mitul A; Nestor, Peter J; Clark, Luke; Sahakian, Barbara J

    2006-03-01

    The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, double-blind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in 'normalizing' the decision-making behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the 'somatic marker' hypothesis of impaired decision-making following orbitofrontal dysfunction.

  16. Impairment of prosocial sentiments is associated with frontopolar and septal damage in frontotemporal dementia

    Science.gov (United States)

    Moll, Jorge; Zahn, Roland; de Oliveira-Souza, Ricardo; Bramati, Ivanei E.; Krueger, Frank; Tura, Bernardo; Cavanagh, Alyson L.; Grafman, Jordan

    2010-01-01

    Poets and philosophers have long acknowledged moral sentiments as key motivators of human social behavior. Prosocial sentiments, which include guilt, pity and embarrassment, enable us to care about others and to be concerned about our mistakes. Functional imaging studies have implicated frontopolar, ventromedial frontal and basal forebrain regions in the experience of prosocial sentiments. Patients with lesions of the frontopolar and ventromedial frontal areas were observed to behave inappropriately and less prosocially, which could be attributed to a generalized emotional blunting. Direct experimental evidence for brain regions distinctively associated with moral sentiment impairments is lacking, however. We investigated this issue in patients with the behavioral variant of frontotemporal dementia, a disorder in which early and selective impairments of social conduct are consistently observed. Using a novel moral sentiment task, we show that the degree of impairment of prosocial sentiments is associated with the degree of damage to frontopolar cortex and septal area, as assessed with 18-Fluoro-Deoxy-Glucose-Positron Emission Tomography, an established measure of neurodegenerative damage. This effect was dissociable from impairment of other-critical feelings (anger and disgust), which was in turn associated with dorsomedial prefrontal and amygdala dysfunction. Our findings suggest a critical role of the frontopolar cortex and septal region in enabling prosocial sentiments, a fundamental component of moral conscience. PMID:20728544

  17. Functional connectivity and microstructural white matter changes in phenocopy frontotemporal dementia

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    Meijboom, R.; Steketee, R.M.E.; Lugt, A. van der; Smits, M. [Erasmus MC - University Medical Centre, Radiology and Nuclear Medicine, Rotterdam (Netherlands); Koning, I. de [Erasmus MC - University Medical Centre, Neuropsychology, Rotterdam (Netherlands); Osse, R.J. [Erasmus MC - University Medical Centre, Psychiatry, Rotterdam (Netherlands); Jiskoot, L.C. [Erasmus MC - University Medical Centre, Neuropsychology, Rotterdam (Netherlands); Erasmus MC - University Medical Centre, Neurology, Rotterdam (Netherlands); Jong, F.J. de; Swieten, J.C. van [Erasmus MC - University Medical Centre, Neurology, Rotterdam (Netherlands)

    2017-04-15

    Phenocopy frontotemporal dementia (phFTD) is a rare and poorly understood clinical syndrome. PhFTD shows core behavioural variant FTD (bvFTD) symptoms without associated cognitive deficits and brain abnormalities on conventional MRI and without progression. In contrast to phFTD, functional connectivity and white matter (WM) microstructural abnormalities have been observed in bvFTD. We hypothesise that phFTD belongs to the same disease spectrum as bvFTD and investigated whether functional connectivity and microstructural WM changes similar to bvFTD are present in phFTD. Seven phFTD patients without progression or alternative psychiatric diagnosis, 12 bvFTD patients and 17 controls underwent resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Default mode network (DMN) connectivity and WM measures were compared between groups. PhFTD showed subtly increased DMN connectivity and subtle microstructural changes in frontal WM tracts. BvFTD showed abnormalities in similar regions as phFTD, but had lower increased DMN connectivity and more extensive microstructural WM changes. Our findings can be interpreted as neuropathological changes in phFTD and are in support of the hypothesis that phFTD and bvFTD may belong to the same disease spectrum. Advanced MRI techniques, objectively identifying brain abnormalities, would therefore be potentially suited to improve the diagnosis of phFTD. (orig.)

  18. Brain perfusion SPECT with Brodmann areas analysis in differentiating frontotemporal dementia subtypes.

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    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Kapsalaki, Eftychia; Fezoulidis, Ioannis; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2014-01-01

    Despite the known validity of clinical diagnostic criteria, significant overlap of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in several cases, resulting in great uncertainty of the diagnostic boundaries. We evaluated the perfusion between FTD subtypes using brain perfusion (99m)Tc-HMPAO SPECT with Brodmann areas (BA) mapping. NeuroGam software was applied on single photon emission computed tomographic (SPECT) studies for the semi-quantitative evaluation of perfusion in BA and the comparison with the software's normal database. We studied 91 consecutive FTD patients: 21 with behavioural variants (bvFTD), 39 with language variants (lvFTD) [12 with progressive non-fluent aphasia (PNFA), 27 with semantic dementia (SD)], and 31 patients with progressive supranuclear palsy (PSP)/corticobasal degeneration (CBD). Stepwise logistic regression analyses showed that the BA 28L and 32R could independently differentiate bvFTD from lvFTD, while the BA 8R and 25R could discriminate bvFTD from SD and PNFA, respectively. Additionally, BA 7R and 32R were found to discriminate bvFTD from CBD/PSP. The only BA that could differentiate SD from PNFA was 6L. BA 6R and 20L were found to independently differentiate CBD/PSP from lvFTD. Moreover, BA 20L and 22R could discriminate CBD/PSP from PNFA, while BA 6R, 20L and 45R were found to independently discriminate CBD/PSP from SD. Brain perfusion SPECT with BA mapping can be a useful additional tool in differentiating FTD variants by improving the definition of brain areas that are specifically implicated, resulting in a more accurate differential diagnosis in atypical or uncertain forms of FTD.

  19. All Is Not Lost: Positive Behaviors in Alzheimer’s Disease and Behavioral-Variant Frontotemporal Dementia with Disease Severity

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    Midorikawa, Akira; Leyton, Cristian E.; Foxe, David; Landin-Romero, Ramon; Hodges, John R.; Piguet, Olivier

    2016-01-01

    Background: Anecdotal evidence indicates that some patients with dementia exhibit novel or increased positive behaviors, such as painting or singing, after the disease onset. Due to the lack of objective measures, however, the frequency and nature of these changes has not been formally investigated. Objective: This study aimed to systematically identify changes in these behaviors in the two most common younger-onset dementia syndromes: Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD). Methods: Sixty-three caregivers of patients with dementia (32 caregivers of AD patients and 31 caregivers of bvFTD patients) participated in the study. Caregivers rated the presence and frequency of positive and negative behavior changes after the onset of dementia using the Hypersensory and Social/Emotional Scale (HSS) questionnaire, focusing on three domains: sensory processing, cognitive skills, and social/emotional processing. Six composites scores were obtained reflecting these three domains (two composite scores for each domain). Differences across scores and ratios of increased and decreased behaviors were analyzed between AD and bvFTD, at different disease severity levels. Results: After disease onset, significant changes in the sensory processing domain were observed across disease severity levels, particularly in AD. Composite scores of the other domains did not change significantly. Importantly, however, some novel or increased positive behaviors were present in between 10% (Music activities) and 70% (Hypersensitivity) of AD and bvFTD patients, regardless of disease severity. Conclusions: We provide the first systematic investigation of positive behaviors in AD and bvFTD. The newly developed HSS questionnaire is a valid measure to characterize changes and progression of positive behaviors in patients with dementia. PMID:27472884

  20. Analysis of a case series of behavioral variant frontotemporal dementia: Emphasis on diagnostic delay

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    Henrique Cerqueira Guimarães

    Full Text Available ABSTRACT Introduction: Despite many advances in the characterization of the behavioral variant of frontotemporal dementia (bvFTD, the diagnosis of this syndrome poses a significant challenge, while delays or diagnostic mistakes may impact the proper clinical management of these patients. Objective: To describe the clinical profile at first evaluation of a sample of patients with bvFTD from a specialized outpatient neurological unit, with emphasis on the analysis of the delay between the onset of symptoms and diagnosis. Methods: We selected 31 patients that fulfilled international consensus criteria for possible or probable bvFTD. Patients' medical admission sheets were thoroughly reviewed. Results: Patients' mean age was 67.9±8.2 years; 16 (51.6% were men. Mean number of years of formal education was 7.7±4.0 years. Mean age at onset was 62.2±7.7 years, indicating a mean of 5.8 years of diagnostic delay. Thirteen patients (41.9% presented with initial behavioral complaints only, eleven patients (35.5% had mixed behavioral and memory complaints, five patients (16.1% presented with memory complaints only, and two patient (6.4% had behavioral and speech problems. Nine patients (29% were admitted with alternative diagnoses. Mean and standard deviation scores for the mini-mental state examination, animal category fluency and memory test for drawings (five-minute delayed recall were 19.3±6.3, 8.3±4.1 and 3.7±2.7, respectively. Conclusion: Most patients from this sample were evaluated almost six years after the onset of symptoms and performed poorly on both cognitive screening tests and functional evaluation measures.

  1. Loss of TBK1 is a frequent cause of frontotemporal dementia in a Belgian cohort

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    Gijselinck, Ilse; Van Mossevelde, Sara; van der Zee, Julie; Sieben, Anne; Philtjens, Stéphanie; Heeman, Bavo; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; De Baets, Greet; Bäumer, Veerle; Cuijt, Ivy; Van den Broeck, Marleen; Peeters, Karin; Mattheijssens, Maria; Rousseau, Frederic; Vandenberghe, Rik; De Jonghe, Peter; Cras, Patrick; De Deyn, Peter P.; Martin, Jean-Jacques

    2015-01-01

    Objective: To assess the genetic contribution of TBK1, a gene implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and FTD-ALS, in Belgian FTD and ALS patient cohorts containing a significant part of genetically unresolved patients. Methods: We sequenced TBK1 in a hospital-based cohort of 482 unrelated patients with FTD and FTD-ALS and 147 patients with ALS and an extended Belgian FTD-ALS family DR158. We followed up mutation carriers by segregation studies, transcript and protein expression analysis, and immunohistochemistry. Results: We identified 11 patients carrying a loss-of-function (LOF) mutation resulting in an overall mutation frequency of 1.7% (11/629), 1.1% in patients with FTD (5/460), 3.4% in patients with ALS (5/147), and 4.5% in patients with FTD-ALS (1/22). We found 1 LOF mutation, p.Glu643del, in 6 unrelated patients segregating with disease in family DR158. Of 2 mutation carriers, brain and spinal cord was characterized by TDP-43-positive pathology. The LOF mutations including the p.Glu643del mutation led to loss of transcript or protein in blood and brain. Conclusions: TBK1 LOF mutations are the third most frequent cause of clinical FTD in the Belgian clinically based patient cohort, after C9orf72 and GRN, and the second most common cause of clinical ALS after C9orf72. These findings reinforce that FTD and ALS belong to the same disease continuum. PMID:26581300

  2. Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia.

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    Cook, Casey; Dunmore, Judy H; Murray, Melissa E; Scheffel, Kristyn; Shukoor, Nawsheen; Tong, Jimei; Castanedes-Casey, Monica; Phillips, Virginia; Rousseau, Linda; Penuliar, Michael S; Kurti, Aishe; Dickson, Dennis W; Petrucelli, Leonard; Fryer, John D

    2014-07-01

    Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. The established and emerging roles of astrocytes and microglia in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

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    Rowan Andrew Warren Radford

    2015-10-01

    Full Text Available Amyotrophic lateral sclerosis (ALS and Frontotemporal Dementia (FTD are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and vice versa, recent genetic discoveries conclusive link the two diseases, and several common molecular players have been identified (TDP-43, FUS, C9ORF72.The definitive aetiologies of ALS and FTD are currently unknown and both disorders lack a cure. Glia, specifically astrocytes and microglia are heavily implicated in the onset and progression of neurodegeneration witnessed in ALS and FTD. In this review, we summarise the current understanding of the role of microglia and astrocytes involved in ALS and FTD, highlighting their recent implications in neuroinflammation, alterations in waste clearance involving phagocytosis and the newly described glymphatic system, and vascular abnormalities. Elucidating the precise mechanisms of how astrocytes and microglia are involved in ALS and FTD will be crucial in characterising these two disorders and may represent more effective interventions for disease progression and treatment options in the future.

  4. Atypical Huntington's disease with the clinical presentation of behavioural variant of frontotemporal dementia.

    Science.gov (United States)

    Sutovsky, Stanislav; Smolek, Tomas; Alafuzoff, Irina; Blaho, Andrej; Parrak, Vojtech; Turcani, Peter; Palkovic, Michal; Petrovic, Robert; Novak, Michal; Zilka, Norbert

    2016-12-01

    Huntington's disease is an incurable, adult-onset, autosomal dominant inherited disorder caused by an expanded trinucleotide repeat (CAG). In this study, we describe a Huntington's disease patient displaying clinical symptoms of the behavioural variant of frontotemporal dementia in the absence of tremor and ataxia. The clinical onset was at the age of 36 years and the disease progressed slowly (18 years). Genetic testing revealed expanded trinucleotide CAG repeats in the Huntingtin gene, together with a Glu318Gly polymorphism in presenilin 1. Neuropathological assessment revealed extensive amyloid β (Aβ) aggregates in all cortical regions. No inclusions displaying hyperphosphorylated tau or phosphorylated transactive response DNA-binding protein 43 (TDP43) were found. A high number of p62 (sequestosome 1) immunopositive intranuclear inclusions were seen mainly in the cortex, while subcortical areas were affected to a lesser extent. Confocal microscopy revealed that the majority of p62 intranuclear lesions co-localised with the fused-in-sarcoma protein (FUS) immunostaining. The morphology of the inclusions resembled intranuclear aggregates in Huntington's disease. The presented proband suffered from Huntington's disease showed atypical distribution of FUS positive intranuclear aggregates in the cortical areas with concomitant Alzheimer's disease pathology.

  5. Genetics insight into the amyotrophic lateral sclerosis/frontotemporal dementia spectrum.

    Science.gov (United States)

    Ji, Ai-Ling; Zhang, Xia; Chen, Wei-Wei; Huang, Wen-Juan

    2017-03-01

    Recent genetic discoveries have dramatically changed our understanding of two major neurodegenerative conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are common, devastating diseases of the brain. For decades, ALS and FTD were classified as movement and cognitive disorders, respectively, due to their distinct clinical phenotypes. The recent identification of chromosome 9 open reading frame 72 (C9orf72) as the major gene causative of familial forms of ALS and FTD uncovered a new reality of a continuous FTD/ALS spectrum. The finding that up to 50% of all patients present some degree of ALS and FTD phenotypes supports this ALS/FTD continuum. Now >100 genes are known to contribute to ALS/FTD, with a few major contributors that are reviewed below. The low penetrance of C9orf72 mutations, its contribution to sporadic cases, and its combination with other genes support an oligogenic model where two or more genes contribute to disease risk, onset, progression and phenotype: from 'pure' ALS or FTD to combined ALS/FTD. These advances in the genetics of ALS/FTD will soon lead to a better mechanistic understanding of the pathobiology of the disease, which should result in the development of effective therapies in the near future.

  6. TERRA INCOGNITA - CEREBELLAR CONTRIBUTIONS TO NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION IN BEHAVIOURAL VARIANT FRONTOTEMPORAL DEMENTIA

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    Rachel H Tan

    2015-07-01

    Full Text Available Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioural variant frontotemporal dementia (bvFTD, a disease which is characterized by cognitive and neuropsychiatric deficits. The present study assessed whether degeneration in specific cerebellar subregions associate with indices of cognition and neuropsychiatric performance in bvFTD. Our results demonstrate a relationship between cognitive and neuropsychiatric decline across various domains of memory, language, emotion, executive, visuospatial function and motivation and the degree of grey matter degeneration in cerebellar lobules V-VII. Most notably, bilateral cerebellar lobule VII and the posterior vermis emerged as distinct for memory processes, the right cerebellar hemisphere underpinned emotion, and the posterior vermis was highlighted in language dysfunction in bvFTD. Based on cortico-cerebellar connectivity maps, these findings in the cerebellum are consistent with the neural connections with the cortices involved in these domains in patients with bvFTD. Overall, the present study underscores the significance of cortical-cerebellar networks associated with cognition and neuropsychiatric dysfunction in bvFTD.

  7. The established and emerging roles of astrocytes and microglia in amyotrophic lateral sclerosis and frontotemporal dementia.

    Science.gov (United States)

    Radford, Rowan A; Morsch, Marco; Rayner, Stephanie L; Cole, Nicholas J; Pountney, Dean L; Chung, Roger S

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and vice versa. Recent genetic discoveries conclusively link the two diseases, and several common molecular players have been identified (TDP-43, FUS, C9ORF72). The definitive etiologies of ALS and FTD are currently unknown and both disorders lack a cure. Glia, specifically astrocytes and microglia are heavily implicated in the onset and progression of neurodegeneration witnessed in ALS and FTD. In this review, we summarize the current understanding of the role of microglia and astrocytes involved in ALS and FTD, highlighting their recent implications in neuroinflammation, alterations in waste clearance involving phagocytosis and the newly described glymphatic system, and vascular abnormalities. Elucidating the precise mechanisms of how astrocytes and microglia are involved in ALS and FTD will be crucial in characterizing these two disorders and may represent more effective interventions for disease progression and treatment options in the future.

  8. Profiling Speech and Pausing in Amyotrophic Lateral Sclerosis (ALS and Frontotemporal Dementia (FTD.

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    Yana Yunusova

    Full Text Available This study examines reading aloud in patients with amyotrophic lateral sclerosis (ALS and those with frontotemporal dementia (FTD in order to determine whether differences in patterns of speaking and pausing exist between patients with primary motor vs. primary cognitive-linguistic deficits, and in contrast to healthy controls.136 participants were included in the study: 33 controls, 85 patients with ALS, and 18 patients with either the behavioural variant of FTD (FTD-BV or progressive nonfluent aphasia (FTD-PNFA. Participants with ALS were further divided into 4 non-overlapping subgroups--mild, respiratory, bulbar (with oral-motor deficit and bulbar-respiratory--based on the presence and severity of motor bulbar or respiratory signs. All participants read a passage aloud. Custom-made software was used to perform speech and pause analyses, and this provided measures of speaking and articulatory rates, duration of speech, and number and duration of pauses. These measures were statistically compared in different subgroups of patients.The results revealed clear differences between patient groups and healthy controls on the passage reading task. A speech-based motor function measure (i.e., articulatory rate was able to distinguish patients with bulbar ALS or FTD-PNFA from those with respiratory ALS or FTD-BV. Distinguishing the disordered groups proved challenging based on the pausing measures.This study demonstrated the use of speech measures in the identification of those with an oral-motor deficit, and showed the usefulness of performing a relatively simple reading test to assess speech versus pause behaviors across the ALS-FTD disease continuum. The findings also suggest that motor speech assessment should be performed as part of the diagnostic workup for patients with FTD.

  9. Profiling Speech and Pausing in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)

    Science.gov (United States)

    Yunusova, Yana; Graham, Naida L.; Shellikeri, Sanjana; Phuong, Kent; Kulkarni, Madhura; Rochon, Elizabeth; Tang-Wai, David F.; Chow, Tiffany W.; Black, Sandra E.; Zinman, Lorne H.; Green, Jordan R.

    2016-01-01

    Objective This study examines reading aloud in patients with amyotrophic lateral sclerosis (ALS) and those with frontotemporal dementia (FTD) in order to determine whether differences in patterns of speaking and pausing exist between patients with primary motor vs. primary cognitive-linguistic deficits, and in contrast to healthy controls. Design 136 participants were included in the study: 33 controls, 85 patients with ALS, and 18 patients with either the behavioural variant of FTD (FTD-BV) or progressive nonfluent aphasia (FTD-PNFA). Participants with ALS were further divided into 4 non-overlapping subgroups—mild, respiratory, bulbar (with oral-motor deficit) and bulbar-respiratory—based on the presence and severity of motor bulbar or respiratory signs. All participants read a passage aloud. Custom-made software was used to perform speech and pause analyses, and this provided measures of speaking and articulatory rates, duration of speech, and number and duration of pauses. These measures were statistically compared in different subgroups of patients. Results The results revealed clear differences between patient groups and healthy controls on the passage reading task. A speech-based motor function measure (i.e., articulatory rate) was able to distinguish patients with bulbar ALS or FTD-PNFA from those with respiratory ALS or FTD-BV. Distinguishing the disordered groups proved challenging based on the pausing measures. Conclusions and Relevance This study demonstrated the use of speech measures in the identification of those with an oral-motor deficit, and showed the usefulness of performing a relatively simple reading test to assess speech versus pause behaviors across the ALS—FTD disease continuum. The findings also suggest that motor speech assessment should be performed as part of the diagnostic workup for patients with FTD. PMID:26789001

  10. Orbitofrontal and limbic signatures of empathic concern and intentional harm in the behavioral variant frontotemporal dementia.

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    Baez, Sandra; Morales, Juan P; Slachevsky, Andrea; Torralva, Teresa; Matus, Cristian; Manes, Facundo; Ibanez, Agustin

    2016-02-01

    Perceiving and evaluating intentional harms in an interpersonal context engages both cognitive and emotional domains. This process involves inference of intentions, moral judgment, and, crucially, empathy towards others' suffering. This latter skill is notably impaired in behavioral variant frontotemporal dementia (bvFTD). However, the relationship between regional brain atrophy in bvFTD and deficits in the above-mentioned abilities is not well understood. The present study investigated how gray matter (GM) atrophy in bvFTD patients correlates with the perception and evaluation of harmful actions (attribution of intentionality, evaluation of harmful behavior, empathic concern, and moral judgment). First, we compared the behavioral performance of 26 bvFTD patients and 23 healthy controls on an experimental task (ET) indexing intentionality, empathy, and moral cognition during evaluation of harmful actions. Second, we compared GM volume in patients and controls using voxel-based morphometry (VBM). Third, we examined brain regions where atrophy might be associated with specific impairments in the patient group. Finally, we explored whether the patients' deficits in intentionality comprehension and empathic concern could be partially explained by regional GM atrophy or impairments in other relevant factors, such as executive functions (EFs). In bvFTD patients, atrophy of limbic structures (amygdala and anterior paracingulate cortex--APC) was related to impairments in intentionality comprehension, while atrophy of the orbitofrontal cortex (OFC) was associated with empathic concern deficits. Intentionality comprehension impairments were predicted by EFs and orbitofrontal atrophy predicted deficits in empathic concern. Thus, although the perception and evaluation of harmful actions are variously compromised in bvFTD, deficits in empathic concern may be central to this syndrome as they are associated with one of the earliest atrophied region. More generally, our results

  11. False recognition in behavioural variant frontotemporal dementia and Alzheimer’s disease – disinhibition or amnesia?

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    Emma C Flanagan

    2016-07-01

    Full Text Available Episodic memory recall processes in Alzheimer’s disease (AD and behavioural variant frontotemporal dementia (bvFTD can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT in 39 bvFTD, 77 AD and 61 control participants from two centres (India, Australia, as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits - false-positives. Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients.

  12. Adaptation and validation of a Spanish-language version of the Frontotemporal Dementia Rating Scale (FTD-FRS).

    Science.gov (United States)

    Turró-Garriga, O; Hermoso Contreras, C; Olives Cladera, J; Mioshi, E; Pelegrín Valero, C; Olivera Pueyo, J; Garre-Olmo, J; Sánchez-Valle, R

    2017-06-01

    The Frontotemporal Dementia Rating Scale (FTD-FRS) is a tool designed to aid with clinical staging and assessment of the progression of frontotemporal dementia (FTD-FRS). Present a multicentre adaptation and validation study of a Spanish version of the FRS. The adapted version was created using 2 translation-back translation processes (English to Spanish, Spanish to English) and verified by the scale's original authors. We validated the adapted version in a sample of consecutive patients diagnosed with FTD. The procedure included evaluating internal consistency, testing unidimensionality with the Rasch model, analysing construct validity and discriminant validity, and calculating the degree of agreement between the Clinical Dementia Rating scale (CDR) and FTD-FRS for FTD cases. The study included 60 patients with DFT. The mean score on the FRS was 12.1 points (SD=6.5; range, 2-25) with inter-group differences (F=120.3; df=3; P<.001). Cronbach's alpha was 0.897 and principal component analysis of residuals delivered an acceptable eigenvalue for 5 contrasts (1.6-2.7) and 36.1% raw variance. FRS was correlated with the Mini-mental State Examination (r=0.572; P<.001) and functional capacity (DAD; r=0.790; P<.001). FTD-FRS also showed a significant correlation with CDR (r=-0.641; P<.001), but we did observe variability in the severity levels; cases appeared to be less severe according to the CDR than when measured with the FTD-FRS (kappa=0.055). This process of validating the Spanish translation of the FTD-FRS yielded satisfactory results for validity and unidimensionality (severity) in the assessment of patients with FTD. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Episodic future thinking is impaired in the behavioural variant of frontotemporal dementia.

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    Irish, Muireann; Hodges, John R; Piguet, Olivier

    2013-10-01

    Remembering the past and imagining the future are complex endeavours proposed to rely on a core neurobiological brain system. In the behavioural variant of frontotemporal dementia (bvFTD), regional patterns of brain atrophy affect medial prefrontal and temporal cortices of this core network. While autobiographical memory impairments have been documented in bvFTD, it remains unknown whether the ability to imagine future events is also compromised. Here, we investigated episodic future thinking in 10 bvFTD patients and contrasted their performance with Alzheimer's disease (AD, n = 10) and healthy matched Control (n = 10) participants. Participants were asked to remember 3 events from the previous year and to envisage 3 possible events that could occur in the next year. Both patient groups showed equivalent episodic detail performance for the retrieval of past events and the simulation of possible future episodes. Patients with bvFTD, however, showed additional impairments for the generation of external (non-episodic) details irrespective of condition. Voxel-based morphometry analyses revealed divergent neural correlates of episodic past and future thinking performance specific to each patient group. Atrophy in the posterior cingulate cortex was implicated in the disruption of past and future thinking in AD. In contrast, in bvFTD, disruption of past retrieval correlated with atrophy in medial prefrontal regions, whereas future thinking deficits were associated with atrophy of frontopolar, medial temporal regions including the right hippocampus, and lateral temporal and occipital cortices. Our results point to the involvement of multiple brain regions in facilitating retrieval of past, and simulation of future, events. Damage to any of these key regions thus adversely affects the ability to engage in personally relevant mental time travel.

  14. The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine.

    Science.gov (United States)

    Hedges, Erin C; Mehler, Vera J; Nishimura, Agnes L

    2016-01-01

    In recent years several genes have linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular pathways. Thus, as never before, compounds with potential applications for regenerative medicine can be specifically tailored in patient derived cultures. In this review, we discuss how patient specific induced pluripotent stem cells (iPSCs) have been used to model ALS and FTD and the most recent drug screening targets for these diseases. We also discuss how an iPSC bank would improve the quality of the available cell lines and how it would increase knowledge about the ALS/FTD disease spectrum.

  15. The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine

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    Erin C. Hedges

    2016-01-01

    Full Text Available In recent years several genes have linked amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular pathways. Thus, as never before, compounds with potential applications for regenerative medicine can be specifically tailored in patient derived cultures. In this review, we discuss how patient specific induced pluripotent stem cells (iPSCs have been used to model ALS and FTD and the most recent drug screening targets for these diseases. We also discuss how an iPSC bank would improve the quality of the available cell lines and how it would increase knowledge about the ALS/FTD disease spectrum.

  16. Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease

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    Neal Scott J

    2006-08-01

    Full Text Available Abstract Background Many cases of frontotemporal dementia (FTD are familial, often with an autosomal dominant pattern of inheritance. Some are due to a mutation in the tau- encoding gene, on chromosome 17, and show an accumulation of abnormal tau in brain tissue (FTDP-17T. Most of the remaining familial cases do not exhibit tau pathology, but display neuropathology similar to patients with dementia and motor neuron disease, characterized by the presence of ubiquitin-immunoreactive (ub-ir, dystrophic neurites and neuronal cytoplasmic inclusions in the neocortex and hippocampus (FTLD-U. Recently, we described a subset of patients with familial FTD with autopsy-proven FTLD-U pathology and with the additional finding of ub-ir neuronal intranuclear inclusions (NII. NII are a characteristic feature of several other neurodegenerative conditions for which the genetic basis is abnormal expansion of a polyglutamine-encoding trinucleotide repeat region. The genetic basis of familial FTLD-U is currently not known, however the presence of NII suggests that a subset of cases may represent a polyglutamine expansion disease. Methods We studied DNA and post mortem brain tissue from 5 affected members of 4 different families with NII and one affected individual with familial FTLD-U without NII. Patient DNA was screened for CAA/CAG trinucleotide expansion in a set of candidate genes identified using a genome-wide computational approach. Genes containing CAA/CAG trinucleotide repeats encoding at least five glutamines were examined (n = 63, including the nine genes currently known to be associated with human disease. CAA/CAG tract sizes were compared with published normal values (where available and with those of healthy controls (n = 94. High-resolution agarose gel electrophoresis was used to measure allele size (number of CAA/CAG repeats. For any alleles estimated to be equal to or larger than the maximum measured in the control population, the CAA/CAG tract

  17. Usefulness of Measurement of the Temporal Stem on Magnetic Resonance Imaging in the Diagnosis of Frontotemporal Dementia

    Energy Technology Data Exchange (ETDEWEB)

    Hayashida, Y.; Hirai, T.; Korogi, Y.; Kimura, T.; Ishizuka, K.; Kawanaka, K.; Yamura, M.; Kitajima, M.; Ikushima, I.; Yamashita, Y. [Graduate School of Medical Sciences, Kumamoto Univ. (Japan). Depts. of Diagnostic Radiology and Psychiatry

    2006-07-15

    Purpose: To investigate whether measurements of brain structures on routine magnetic resonance (MR) images can be used to distinguish between normal subjects and patients with frontotemporal dementia (FTD) or Alzheimer's disease (AD). Material and Methods: MRI studies were performed on 30 patients with dementia (FTD, n = 15; AD, n = 15) and 15 age-matched controls. Width measurements, obtained at the corpus callosum, the cingulate gyri, the hippocampi, and the temporal stem of the anterior temporal lobes, were compared among FTD and AD patients and control subjects on oblique-coronal T2-weighted images. Results: The width of the temporal stem was significantly narrower in FTD than in AD patients and control subjects (6.3{+-}1.3 mm, 7.8{+-}1.1 mm, and 8.2{+-}0.9 mm, respectively) ( P <0.05), although there was some overlapping between AD and FTD patients. All patients whose temporal stem width was <6 mm had FTD. While the width of the corpus callosum, cingulate gyri, and hippocampi was significantly narrower in patients with AD and FTD than in the controls, there was no significant difference between the AD and FTD patients. Conclusion: The width of the temporal stem was significantly narrower in patients with FTD than in those with AD and controls. The described measurements can easily be obtained and may be useful for the diagnosis of FTD.

  18. Grey and White Matter Changes across the Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Continuum

    Science.gov (United States)

    Lillo, Patricia; Mioshi, Eneida; Burrell, James R.; Kiernan, Matthew C.; Hodges, John R.; Hornberger, Michael

    2012-01-01

    There is increasing evidence that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a clinical, pathological and genetic continuum with patients of one disease exhibiting features of the other. Nevertheless, to date, the underlying grey matter and white matter changes across the ALS-FTD disease continuum have not been explored. In this study fifty-three participants with ALS (n = 10), ALS-FTD (n = 10) and behavioural variant FTD (bvFTD; n = 15) as well as controls (n = 18), underwent detailed clinical assessment plus structural imaging using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis of magnetic resonance brain imaging to examine grey and white matter differences and commonalities across the continuum. Importantly, patient groups were matched for age, education, gender and disease duration. VBM and DTI results showed that changes in the ALS group were confined mainly to the motor cortex and anterior cingulate as well as their underlying white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white matter changes involving frontal and temporal lobes. Extensive prefrontal cortex changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD could be distinguished from ALS by additional temporal lobe grey and white matter changes. Finally, ALS could be mainly distinguished from the other two groups by corticospinal tract degeneration. The present study shows for the first time that FTD and ALS overlap in anterior cingulate, motor cortex and related white matter tract changes across the whole continuum. Nevertheless, frontal and temporal atrophy as well as corticospinal tract degeneration emerged as marker for subtype classification, which will inform future diagnosis and target disease management across the continuum. PMID:22952843

  19. Grey and white matter changes across the amyotrophic lateral sclerosis-frontotemporal dementia continuum.

    Directory of Open Access Journals (Sweden)

    Patricia Lillo

    Full Text Available There is increasing evidence that amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD lie on a clinical, pathological and genetic continuum with patients of one disease exhibiting features of the other. Nevertheless, to date, the underlying grey matter and white matter changes across the ALS-FTD disease continuum have not been explored. In this study fifty-three participants with ALS (n = 10, ALS-FTD (n = 10 and behavioural variant FTD (bvFTD; n = 15 as well as controls (n = 18, underwent detailed clinical assessment plus structural imaging using voxel-based morphometry (VBM and diffusion tensor imaging (DTI analysis of magnetic resonance brain imaging to examine grey and white matter differences and commonalities across the continuum. Importantly, patient groups were matched for age, education, gender and disease duration. VBM and DTI results showed that changes in the ALS group were confined mainly to the motor cortex and anterior cingulate as well as their underlying white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white matter changes involving frontal and temporal lobes. Extensive prefrontal cortex changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD could be distinguished from ALS by additional temporal lobe grey and white matter changes. Finally, ALS could be mainly distinguished from the other two groups by corticospinal tract degeneration. The present study shows for the first time that FTD and ALS overlap in anterior cingulate, motor cortex and related white matter tract changes across the whole continuum. Nevertheless, frontal and temporal atrophy as well as corticospinal tract degeneration emerged as marker for subtype classification, which will inform future diagnosis and target disease management across the continuum.

  20. Fronto-striatal atrophy in behavioural variant frontotemporal dementia & Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Maxime eBertoux

    2015-07-01

    Full Text Available Behavioural variant frontotemporal dementia (bvFTD has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD. Considering the critical role the striatum has in cognition and behaviour, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. By contrast, AD showed few fronto-striatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal-ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms.

  1. Differential automatic diagnosis between Alzheimer's disease and frontotemporal dementia based on perfusion SPECT images.

    Science.gov (United States)

    Horn, Jean-François; Habert, Marie-Odile; Kas, Aurélie; Malek, Zoulikha; Maksud, Philippe; Lacomblez, Lucette; Giron, Alain; Fertil, Bernard

    2009-10-01

    Alzheimer's disease (AD) and frontotemporal dementia (FTD) are among the most frequent neurodegenerative cognitive disorders, but their differential diagnosis is difficult. The aim of this study was to evaluate an automatic method returning the probability that a patient suffers from AD or FTD from the analysis of brain perfusion single photon emission computed tomography images. A set of 116 descriptors corresponding to the average activity in regions of interest was calculated from the images of 82 AD and 91 FTD patients. A set of linear (logistic regression and linear discriminant analysis) and non-linear (support vector machines, k-nearest neighbours, multilayer perceptron and kernel logistic PLS) classification methods was subsequently used to ascertain diagnoses. Validation was carried out by means of the leave-one-out protocol. Diagnoses by the classifier and by four physicians (visual assessment) were compared. Since images were acquired in different hospitals, the impact of the medical centre on the diagnosis of both the classifier and the physicians was investigated. Best results were obtained with support vector machine and partial least squares regression coupled with k-nearest neighbours methods (PLS+K-NN), with an overall accuracy of 88%. PLS+K-NN was however considered as the best method since performances obtained with leave-one-out cross-validation were closer to whole-database learning. The performances of the classifier were higher than those of experts (accuracy ranged from 65 to 72%). Physicians found it more difficult to diagnose the images from centres other than their own, and it affected their performances. The performances obtained by the classifier for the differential diagnosis of AD and FTD were found convincing. It could help physicians in daily practice, particularly when visual assessment is inconclusive, or when dealing with multicentre data.

  2. Frontotemporal dementia and its subtypes: a genome-wide association study

    Science.gov (United States)

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A; Rohrer, Jonathan D; Ramasamy, Adaikalavan; Kwok, John B J; Dobson-Stone, Carol; Brooks, William S; Schofield, Peter R; Halliday, Glenda M; Hodges, John R; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Waldö, Maria Landqvist; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Mann, David M A; Grafman, Jordan; Morris, Christopher M; Attems, Johannes; Griffiths, Timothy D; McKeith, Ian G; Thomas, Alan J; Pietrini, P; Huey, Edward D; Wassermann, Eric M; Baborie, Atik; Jaros, Evelyn; Tierney, Michael C; Pastor, Pau; Razquin, Cristina; Ortega-Cubero, Sara; Alonso, Elena; Perneczky, Robert; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Kurz, Alexander; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Rogaeva, Ekaterina; George-Hyslop, Peter St; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B; Schlachetzki, J C M; Uphill, James; Collinge, John; Mead, S; Danek, Adrian; Van Deerlin, Vivianna M; Grossman, Murray; Trojanowsk, John Q; van der Zee, Julie; Deschamps, William; Van Langenhove, Tim; Cruts, Marc; Van Broeckhoven, Christine; Cappa, Stefano F; Le Ber, Isabelle; Hannequin, Didier; Golfier, Véronique; Vercelletto, Martine; Brice, Alexis; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Piaceri, Irene; Nielsen, Jørgen E; Hjermind, Lena E; Riemenschneider, Matthias; Mayhaus, Manuel; Ibach, Bernd; Gasparoni, Gilles; Pichler, Sabrina; Gu, Wei; Rossor, Martin N; Fox, Nick C; Warren, Jason D; Spillantini, Maria Grazia; Morris, Huw R; Rizzu, Patrizia; Heutink, Peter; Snowden, Julie S; Rollinson, Sara; Richardson, Anna; Gerhard, Alexander; Bruni, Amalia C; Maletta, Raffaele; Frangipane, Francesca; Cupidi, Chiara; Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Conidi, Maria Elena; Smirne, Nicoletta; Rademakers, Rosa; Baker, Matt; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; Knopman, David; Josephs, Keith A; Boeve, Bradley F; Parisi, Joseph E; Seeley, William W; Miller, Bruce L; Karydas, Anna M; Rosen, Howard; van Swieten, John C; Dopper, Elise G P; Seelaar, Harro; Pijnenburg, Yolande AL; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A; Franceschi, M; Postiglione, Alfredo; Milan, Graziella; Sorrentino, Paolo; Kristiansen, Mark; Chiang, Huei-Hsin; Graff, Caroline; Pasquier, Florence; Rollin, Adeline; Deramecourt, Vincent; Lebert, Florence; Kapogiannis, Dimitrios; Ferrucci, Luigi; Pickering-Brown, Stuart; Singleton, Andrew B; Hardy, John; Momeni, Parastoo

    2014-01-01

    Summary Background Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. All participants had European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) and suggestive single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8) that encompassed the HLA locus at 6p21.3 in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC, for the behavioural FTD subtype. Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation incis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and possibly to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of

  3. Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia.

    Science.gov (United States)

    Takeuchi, Ryoko; Toyoshima, Yasuko; Tada, Mari; Tanaka, Hidetomo; Shimizu, Hiroshi; Shiga, Atsushi; Miura, Takeshi; Aoki, Kenju; Aikawa, Akane; Ishizawa, Shin; Ikeuchi, Takeshi; Nishizawa, Masatoyo; Kakita, Akiyoshi; Takahashi, Hitoshi

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD.

  4. Early-stage differentiation between presenile Alzheimer's disease and frontotemporal dementia using arterial spin labeling MRI

    Energy Technology Data Exchange (ETDEWEB)

    Steketee, Rebecca M.E.; Meijboom, Rozanna; Lugt, Aad van der; Smits, Marion [Erasmus MC - University Medical Center, Department of Radiology, PO Box 2040, Rotterdam (Netherlands); Bron, Esther E.; Klein, Stefan [Erasmus MC - University Medical Center, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, PO Box 2040, Rotterdam (Netherlands); Houston, Gavin C. [GE Healthcare, Hatfield (United Kingdom); Mutsaerts, Henri J.M.M. [Academic Medical Center, Department of Radiology, PO Box 22660, Amsterdam (Netherlands); Mendez Orellana, Carolina P. [Erasmus MC - University Medical Center, Department of Radiology, PO Box 2040, Rotterdam (Netherlands); Erasmus MC - University Medical Center, Department of Neurology, PO Box 2040, Rotterdam (Netherlands); Jong, Frank Jan de; Swieten, John C. van [Erasmus MC - University Medical Center, Department of Neurology, PO Box 2040, Rotterdam (Netherlands)

    2016-01-15

    To investigate arterial spin labeling (ASL)-MRI for the early diagnosis of and differentiation between the two most common types of presenile dementia: Alzheimer's disease (AD) and frontotemporal dementia (FTD), and for distinguishing age-related from pathological perfusion changes. Thirteen AD and 19 FTD patients, and 25 age-matched older and 22 younger controls underwent 3D pseudo-continuous ASL-MRI at 3 T. Gray matter (GM) volume and cerebral blood flow (CBF), corrected for partial volume effects, were quantified in the entire supratentorial cortex and in 10 GM regions. Sensitivity, specificity and diagnostic performance were evaluated in regions showing significant CBF differences between patient groups or between patients and older controls. AD compared with FTD patients had hypoperfusion in the posterior cingulate cortex, differentiating these with a diagnostic performance of 74 %. Compared to older controls, FTD patients showed hypoperfusion in the anterior cingulate cortex, whereas AD patients showed a more widespread regional hypoperfusion as well as atrophy. Regional atrophy was not different between AD and FTD. Diagnostic performance of ASL to differentiate AD or FTD from controls was good (78-85 %). Older controls showed global hypoperfusion compared to young controls. ASL-MRI contributes to early diagnosis of and differentiation between presenile AD and FTD. (orig.)

  5. A decade of genetic counseling in frontotemporal dementia affected families: few counseling requests and much familial opposition to testing.

    Science.gov (United States)

    Riedijk, S R; Niermeijer, M F N; Dooijes, D; Tibben, A

    2009-08-01

    A decade of genetic counseling of frontotemporal dementia (FTD) affected families has generated two important observations. First, the uptake rate for presymptomatic testing for FTD is low in our department of Clinical Genetics at the Erasmus Medical Center in the Netherlands. Second, FTD at-risk counselees reported substantial familial opposition to genetic testing, which is distinct from the attitude in Huntington Disease affected families. We hypothesize that the low acceptance for FTD genetic counseling is consequential to the familial opposition and explain this within the theoretical framework of separation-individuation. Furthermore, we hypothesize that separation-individuation problems do not similarly influence the acceptance of HD genetic counseling, due to the educative role of the well-organised patient organization for HD in the Netherlands. We offer counseling recommendations that serve to facilitate the individuation of the counselee with respect to the FTD genetic test.

  6. [Disruptive sexual behaviour among patients with dementia].

    Science.gov (United States)

    Kämpf, C; Abderhalden, C

    2012-10-01

    In addition to diagnostically decisive cognitive problems, behavioural and psychological symptoms (BPSD) are frequent among people with dementia, including sexually related behavioural problems. This paper provides an overview on the state of knowledge about these problems. Research on this topic is hampered by the absence of unanimous definitions, aetiological classifications, and diagnostic instruments. The wide range of prevalence rates reported (1.8 - 18 %) originate from the heterogenity of study samples as well as in the variety of definitions and instruments employed. Regarding aetiology, dysfunctions in various cortical regions are being discussed. Sexually related behavioural problems are more prevalent in men and among patients with vascular, frontotemporal and Parkinson-associated forms of dementia, as compared with dementias of the Alzheimer type. The pharmacological and non-pharmacological treatment strategies published to date have not been sufficiently studied.

  7. A decade of genetic counseling in frontotemporal dementia affected families: Few counseling requests and much familial opposition to testing

    NARCIS (Netherlands)

    S.R. Riedijk (Samantha); M.F. Niermeijer (Martinus); D. Dooijes (Dennis); A. Tibben (Arend)

    2009-01-01

    textabstractA decade of genetic counseling of frontotemporal dementia (FTD) affected families has generated two important observations. First, the uptake rate for presymptomatic testing for FTD is low in our department of Clinical Genetics at the Erasmus Medical Center in the Netherlands. Second, FT

  8. Multiparametric computer-aided differential diagnosis of Alzheimer’s disease and frontotemporal dementia using structural and advanced MRI

    NARCIS (Netherlands)

    E.E. Bron (Esther); M. Smits (Marion); J.M. Papma (Janne); R.M.E. Steketee (Rebecca); R. Meijboom (Rozanna); M. de Groot (Mirthe); J.C. van Swieten (John); W.J. Niessen (Wiro); S.K. Klein (Stefan)

    2016-01-01

    textabstractObjectives: To investigate the added diagnostic value of arterial spin labelling (ASL) and diffusion tensor imaging (DTI) to structural MRI for computer-aided classification of Alzheimer's disease (AD), frontotemporal dementia (FTD), and controls. Methods: This retrospective study used M

  9. Clinical Utility of Short Social Cognitive Tests in Early Differentiation of Behavioral Variant Frontotemporal Dementia from Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Buhl, Christian; Stokholm, Jette; Gade, Anders

    2013-01-01

    Traditional cognitive tests used in clinical practice may not be sensitive enough for the early differentiation of behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD). A growing body of literature has shown that deficits in various aspects of social cognition can...

  10. Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation

    DEFF Research Database (Denmark)

    Clayton, Emma L; Mancuso, Renzo; Nielsen, Troels Tolstrup

    2017-01-01

    Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD...

  11. A decade of genetic counseling in frontotemporal dementia affected families: Few counseling requests and much familial opposition to testing

    NARCIS (Netherlands)

    S.R. Riedijk (Samantha); M.F. Niermeijer (Martinus); D. Dooijes (Dennis); A. Tibben (Arend)

    2009-01-01

    textabstractA decade of genetic counseling of frontotemporal dementia (FTD) affected families has generated two important observations. First, the uptake rate for presymptomatic testing for FTD is low in our department of Clinical Genetics at the Erasmus Medical Center in the Netherlands. Second,

  12. Genetics Home Reference: GRN-related frontotemporal dementia

    Science.gov (United States)

    ... Neumann M, Kwong LK, Trojanowski JQ, Lee VM, Grossman M. Clinical, genetic, and pathologic characteristics of patients ... Feldman H, Woltjer R, Miller CA, Wood EM, Grossman M, McCluskey L, Clark CM, Neumann M, Danek ...

  13. Overlapping features of frontotemporal dementia and amyotrophic lateral sclerosis

    National Research Council Canada - National Science Library

    Lillo, Patricia; Matamala, José Manuel; Valenzuela, Daniel; Verdugo, Renato; Castillo, José Luis; Ibáñez, Agustín; Slachevsky, Andrea

    2014-01-01

    ...) and amyotrophic lateral sclerosis (ALS) are overlapping multisystem disorders. While 10-15% of ALS patients fulfil criteria for FTD, features of motor neuron disease appear in approximately 15...

  14. Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes.

    Science.gov (United States)

    Thelen, Mathias; Razquin, Cristina; Hernández, Isabel; Gorostidi, Ana; Sánchez-Valle, Raquel; Ortega-Cubero, Sara; Wolfsgruber, Steffen; Drichel, Dmitriy; Fliessbach, Klaus; Duenkel, Tanja; Damian, Marinella; Heilmann, Stefanie; Slotosch, Anja; Lennarz, Martina; Seijo-Martínez, Manuel; Rene, Ramón; Kornhuber, Johannes; Peters, Oliver; Luckhaus, Christian; Jahn, Holger; Hüll, Michael; Rüther, Eckart; Wiltfang, Jens; Lorenzo, Elena; Gascon, Jordi; Lleó, Alberto; Lladó, Albert; Campdelacreu, Jaume; Moreno, Fermin; Ahmadzadehfar, Hojjat; Fortea, Juan; Indakoetxea, Begoña; Heneka, Michael T; Wetter, Axel; Pastor, Maria A; Riverol, Mario; Becker, Tim; Frölich, Lutz; Tárraga, Lluís; Boada, Mercè; Wagner, Michael; Jessen, Frank; Maier, Wolfgang; Clarimón, Jordi; López de Munain, Adolfo; Ruiz, Agustín; Pastor, Pau; Ramirez, Alfredo

    2014-11-01

    Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.

  15. Early onset behavioral variant frontotemporal dementia due to the C9ORF72 hexanucleotide repeat expansion: psychiatric clinical presentations.

    Science.gov (United States)

    Arighi, Andrea; Fumagalli, Giorgio G; Jacini, Francesca; Fenoglio, Chiara; Ghezzi, Laura; Pietroboni, Anna M; De Riz, Milena; Serpente, Maria; Ridolfi, Elisa; Bonsi, Rossana; Bresolin, Nereo; Scarpini, Elio; Galimberti, Daniela

    2012-01-01

    A hexanucleotide repeat expansion in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis or frontotemporal lobar degeneration with or without concomitant motor neuron disease phenotype and TDP-43 based pathology. Here, we report on three cases carrying the hexanucleotide repeat expansion with an atypical presentation consisting in the development of psychiatric symptoms. Patient #1, a 53 year old man with positive family history for dementia, presented with mood deflection, characterized by apathy, social withdraw, and irritability in the last two years. He was diagnosed with "mild cognitive impairment due to depressive syndrome" six months later and subsequently with Alzheimer's disease. Patient #2, a woman with positive family history for dementia, developed behavioral disturbances, aggressiveness, and swearing at 57 years of age. Patient #3 presented, in the absence of brain atrophy, with mystical delirium with auditory hallucinations at 44 years of age, and did not present neurological symptoms over a 7-year follow up. The description of these cases underlines that the hexanucleotide repeat expansion in chromosome 9 could be associated with early onset psychiatric presentations.

  16. Distinct Neurodegenerative Changes in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia Linked to Mutant TAU Protein

    Directory of Open Access Journals (Sweden)

    Marc Ehrlich

    2015-07-01

    Full Text Available Frontotemporal dementia (FTD is a frequent form of early-onset dementia and can be caused by mutations in MAPT encoding the microtubule-associated protein TAU. Because of limited availability of neural cells from patients’ brains, the underlying mechanisms of neurodegeneration in FTD are poorly understood. Here, we derived induced pluripotent stem cells (iPSCs from individuals with FTD-associated MAPT mutations and differentiated them into mature neurons. Patient iPSC-derived neurons demonstrated pronounced TAU pathology with increased fragmentation and phospho-TAU immunoreactivity, decreased neurite extension, and increased but reversible oxidative stress response to inhibition of mitochondrial respiration. Furthermore, FTD neurons showed an activation of the unfolded protein response, and a transcriptome analysis demonstrated distinct, disease-associated gene expression profiles. These findings indicate distinct neurodegenerative changes in FTD caused by mutant TAU and highlight the unique opportunity to use neurons differentiated from patient-specific iPSCs to identify potential targets for drug screening purposes and therapeutic intervention.

  17. Effect of diagnostic criteria on prevalence of frontotemporal dementia in the elderly.

    Science.gov (United States)

    Gislason, Thorsteinn B; Östling, Svante; Börjesson-Hanson, Anne; Sjögren, Magnus; Simoni, Michela; Pantoni, Leonardo; Skoog, Ingmar

    2015-04-01

    Frontotemporal dementia (FTD) is believed to be rare in the elderly, and the influence of different criteria on the prevalence of FTD is unclear. Population-based samples of 70- to 95-year-olds (n = 2462) in Gothenburg, Sweden, underwent neuropsychiatric examinations. Behavioral variant FTD (bvFTD) was diagnosed according to the International Behavioural Variant FTD Criteria Consortium (FTDC), the Frontotemporal Lobe Degeneration Consensus criteria, and the Lund-Manchester Research Criteria. A subset (n = 1074) underwent computerized tomography (CT) of the brain. The prevalence of bvFTD varied between 0.2% and 0.5% at age 70 to 79 years, between 2.5% and 3.6% at age 80 to 89 years, and between 1.7% and 2.2% at age 90 to 95 years. The agreement between different criteria was low to moderate (κ = 0.20-0.42). Among those with bvFTD according to FTDC, 93.3% had frontal and/or temporal lobar atrophy on CT, compared with 12.6% of those without bvFTD (P < .001). The prevalence of bvFTD was higher than expected in this population. To a large extent, different criteria captured different individuals. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  18. Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia.

    Science.gov (United States)

    Benussi, Alberto; Cosseddu, Maura; Filareto, Ilaria; Dell'Era, Valentina; Archetti, Silvana; Sofia Cotelli, Maria; Micheli, Anna; Padovani, Alessandro; Borroni, Barbara

    2016-09-01

    Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long-term potentiation-like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short-interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal-dominant FTD. Ann Neurol 2016;80:472-476.

  19. Constructional apraxia in frontotemporal dementia associated with the C9orf72 mutation: broadening the clinical and neuropsychological phenotype.

    Science.gov (United States)

    Floris, Gianluca; Borghero, Giuseppe; Cannas, Antonino; Di Stefano, Francesca; Ruiu, Elisa; Murru, Maria R; Corongiu, Daniela; Cuccu, Stefania; Tranquilli, Stefania; Sardu, Claudia; Marrosu, Maria G; Chiò, Adriano; Marrosu, Francesco

    2015-03-01

    In our study we analysed clinical and neuropsychological data in a cohort of 57 Sardinian patients with FTD (55 apparently unrelated and two belonging to the same family), who underwent genetic screening for the C9orf72 mutation. Eight out of 56 patients were found positive for the C9orf72 mutation representing 14% of the entire cohort and 31.6% of the familial cases (6/19). C9orf72 mutated patients differed from the other FTD cases of the cohort for a younger age of onset, higher frequency of familial history for FTD and higher prevalence of delusional psychotic symptoms and hallucinations. In the neuropsychological assessment, C9orf72 mutated patients differed from non-mutated for the high frequency of visuospatial dysfunction regarding constructional apraxia (p = 0.02). In conclusion, our study confirms that Sardinian FTD patients have peculiar genetic characteristics and that C9orf72 mutated patients have a distinctive clinical and neuropsychological profile that could help differentiate them from other FTD patients. In our cohort we found that constructional apraxia, rarely reported in FTD, can properly discriminate between C9orf72 mutated and non-mutated patients and contribute to broaden the neuropsychological profile in frontotemporal dementia associated with this mutation.

  20. Accuracy of neuropsychological tests and the Neuropsychiatric Inventory in differential diagnosis between Frontotemporal dementia and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Valéria Santoro Bahia

    Full Text Available Abstract The differential diagnosis between frontotemporal dementia (FTD and Alzheimer's disease (AD is sometimes difficult. Objectives: To verify the accuracy of neuropsychological tests and a behavioral disorders scale in the differential diagnosis between FTLD and AD. Methods: Retrospective data on 12 FTD patients and 12 probable AD patients were analyzed. The scores on neuropsychological tests (MMSE score, reverse digit span, delayed recall for drawings, semantic fluency of animals and the Neuropsychiatric Inventory (NPI in both groups were compared. Results: Both groups had similar performance on neuropsychological tests. All FTD patients and 50% of AD patients had neuropsychiatric abnormalities. The NPI score was 58.0±19.3 for the FTD patients, and 3.6±4.7 for the AD patients (p<0.01. Using a NPI cut-off score of 13, the sensitivity and specificity were 100% in this sample. The four most common neuropsychiatric disturbances in FTD patients were: apathy, aberrant motor behavior, disinhibition and eating abnormalities. Apathy and dysphoria/depression were the most common behavioral symptoms among the AD patients. Conclusions: In this study, NPI was found to be a useful tool for the differential diagnosis between FTD and AD. The neuropsychological tests commonly used in the medical office were unable to distinguish between the two groups.

  1. Distinct clinical and pathological phenotypes in frontotemporal dementia associated with MAPT, PGRN and C9orf72 mutations.

    Science.gov (United States)

    Snowden, Julie S; Adams, Jennifer; Harris, Jennifer; Thompson, Jennifer C; Rollinson, Sara; Richardson, Anna; Jones, Matthew; Neary, David; Mann, David M; Pickering-Brown, Stuart

    2015-01-01

    Our objective was to compare the clinical and pathological characteristics of frontotemporal dementia patients with MAPT, GRN and C9orf72 gene mutations. We carried out a cross-sectional comparative study of 74 gene-positive patients (15 MAPT, 17 GRN and 42 C9orf72). Thirty had post mortem pathological data permitting clinico-pathological correlation. MAPT patients were younger than other groups, and showed more frequent behavioural disinhibition, repetitive and stereotyped behaviours, semantic impairment and temporal predominance of atrophy. GRN patients were older at death and more likely to present with non-fluent aphasia. C9orf72 patients alone showed a co-occurrence of ALS. They showed more psychotic symptoms and irrational behaviour, yet were more often reported clinically as socially appropriate and warm. They showed less dietary change than other groups. C9orf72 patients with and without ALS differed only in frequency of psychosis. Greater clinical overlap was observed between GRN and C9orf72 compared to MAPT cases. MAPT cases had tau and GRN and C9orf72, with one exception, TDP-43 pathology. Non-fluent aphasia was linked to TDP subtype A in both GRN and C9orf72 cases and ALS with subtype B. In conclusion, the findings reinforce clinical heterogeneity in FTD and strengthen evidence that genotype influences clinical presentation. Clinical features may inform targeted genetic testing.

  2. Is the emotion recognition deficit associated with frontotemporal dementia caused by selective inattention to diagnostic facial features?

    Science.gov (United States)

    Oliver, Lindsay D; Virani, Karim; Finger, Elizabeth C; Mitchell, Derek G V

    2014-07-01

    Frontotemporal dementia (FTD) is a debilitating neurodegenerative disorder characterized by severely impaired social and emotional behaviour, including emotion recognition deficits. Though fear recognition impairments seen in particular neurological and developmental disorders can be ameliorated by reallocating attention to critical facial features, the possibility that similar benefits can be conferred to patients with FTD has yet to be explored. In the current study, we examined the impact of presenting distinct regions of the face (whole face, eyes-only, and eyes-removed) on the ability to recognize expressions of anger, fear, disgust, and happiness in 24 patients with FTD and 24 healthy controls. A recognition deficit was demonstrated across emotions by patients with FTD relative to controls. Crucially, removal of diagnostic facial features resulted in an appropriate decline in performance for both groups; furthermore, patients with FTD demonstrated a lack of disproportionate improvement in emotion recognition accuracy as a result of isolating critical facial features relative to controls. Thus, unlike some neurological and developmental disorders featuring amygdala dysfunction, the emotion recognition deficit observed in FTD is not likely driven by selective inattention to critical facial features. Patients with FTD also mislabelled negative facial expressions as happy more often than controls, providing further evidence for abnormalities in the representation of positive affect in FTD. This work suggests that the emotional expression recognition deficit associated with FTD is unlikely to be rectified by adjusting selective attention to diagnostic features, as has proven useful in other select disorders.

  3. A Decade of Genetic Counseling in Frontotemporal Dementia Affected Families: Few Counseling Requests and much Familial Opposition to Testing

    OpenAIRE

    Riedijk, S. R.; Niermeijer, M. F. N.; Dooijes, D.; Tibben, A.

    2009-01-01

    A decade of genetic counseling of frontotemporal dementia (FTD) affected families has generated two important observations. First, the uptake rate for presymptomatic testing for FTD is low in our department of Clinical Genetics at the Erasmus Medical Center in the Netherlands. Second, FTD at-risk counselees reported substantial familial opposition to genetic testing, which is distinct from the attitude in Huntington Disease affected families. We hypothesize that the low acceptance for FTD gen...

  4. Inclusion body myopathy, Paget's disease of the bone and fronto-temporal dementia: a disorder of autophagy

    OpenAIRE

    Ju, Jeong-Sun; Weihl, Conrad C

    2010-01-01

    Inclusion body myopathy associated with Paget's disease of the bone and fronto-temporal dementia (IBMPFD) is a progressive autosomal dominant disorder caused by mutations in p97/VCP (valosin-containing protein). p97/VCP is a member of the AAA+ (ATPase associated with a variety of activities) protein family and participates in multiple cellular processes. One particularly important role for p97/VCP is facilitating intracellular protein degradation. p97/VCP has traditionally been thought to med...

  5. Assessment of free and cued recall in Alzheimer's disease and vascular and frontotemporal dementia with 24-item Grober and Buschke test.

    Science.gov (United States)

    Cerciello, Milena; Isella, Valeria; Proserpi, Alice; Papagno, Costanza

    2017-01-01

    Alzheimer's disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) are the most common forms of dementia. It is well known that memory deficits in AD are different from those in VaD and FTD, especially with respect to cued recall. The aim of this clinical study was to compare the memory performance in 15 AD, 10 VaD and 9 FTD patients and 20 normal controls by means of a 24-item Grober-Buschke test [8]. The patients' groups were comparable in terms of severity of dementia. We considered free and total recall (free plus cued) both in immediate and delayed recall and computed an Index of Sensitivity to Cueing (ISC) [8] for immediate and delayed trials. We assessed whether cued recall predicted the subsequent free recall across our patients' groups. We found that AD patients recalled fewer items from the beginning and were less sensitive to cueing supporting the hypothesis that memory disorders in AD depend on encoding and storage deficit. In immediate recall VaD and FTD showed a similar memory performance and a stronger sensitivity to cueing than AD, suggesting that memory disorders in these patients are due to a difficulty in spontaneously implementing efficient retrieval strategies. However, we found a lower ISC in the delayed recall compared to the immediate trials in VaD than FTD due to a higher forgetting in VaD.

  6. Amnesia in Frontotemporal Dementia with Amyotrophic Lateral Sclerosis, Masquerading Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    A. Yamanami-Irioka

    2011-10-01

    Full Text Available A 68-year-old man with a clinical diagnosis of Alzheimer’s disease (AD later developed amyotrophic lateral sclerosis (ALS, which was confirmed at autopsy at age 72 years. Because neuronal loss and AD-type pathologies (Braak stage II for neurofibrillary tangles were scant, TDP-43-positive intracytoplasmic inclusions in hippocampal dentate granular cells and in neurons in the subiculum and amygdala, even though small in amount, may represent the earliest lesions of ALS-related dementia and could be the cause of dementia in this patient. Although the persistent elevation of creatine kinase from the onset could be a pointer to the presence of motor involvement, more accurate characterization of dementia, which may differentiate ALS-related dementia and AD, is necessary.

  7. Medical management of frontotemporal dementias: the importance of the caregiver in symptom assessment and guidance of treatment strategies.

    Science.gov (United States)

    Jicha, Gregory A

    2011-11-01

    There are no currently Food and Drug Administration-approved or proven off-label treatments for the frontotemporal dementias (FTD). Clinicians, caregivers, and patients struggle regularly to find therapeutic regimens that can alleviate the problematic behavioral and cognitive symptoms associated with these devastating conditions. Success is "hit or miss" and the lessons learned are largely anecdotal to date. Drug discovery in this area has been largely hampered by the heterogeneous clinical presentations and pathological phenotypes of disease that represent significant obstacles to progress in this area. Biologically, plausible treatment strategies include the use of antidepressants (selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor and monoamine oxidase inhibitors), acetylcholinesterase inhibitors, N-methyl-D-aspartic acid antagonists, mood stabilizers, antipsychotics, stimulants, antihypertensives, and agents that may ameliorate the symptoms of parkinsonism, pseudobulbar affect, and motor neuron disease that can often coexist with FTD. These medications all carry potential risks as well as possible benefits for the person suffering from FTD, and a clear understanding of these factors is critical in selecting an appropriate therapeutic regimen to maximize cognition and daily functions, reduce behavioral symptoms, and alleviate caregiver burden in an individual patient. The role of the caregiver in tracking and reporting of symptoms and the effects of individual therapeutic interventions is pivotal in this process. This manuscript highlights the importance of establishing an effective therapeutic partnership between the physician and caregiver in the medical management of the person suffering from FTD.

  8. Familial clustering and genetic risk for dementia in a genetically isolated Dutch population.

    NARCIS (Netherlands)

    K. Sleegers (Kristel); F. Forey; J. Theuns (Jessie); Y.S. Aulchenko (Yurii); S. Rademakers (Suzanne); M. Cruts (Marc); W.A. van Gool (Willem); P. Heutink (Peter); B.A. Oostra (Ben); J.C. van Swieten (John); C.M. van Duijn (Cock); C. van Broeckhoven (Christine)

    2004-01-01

    textabstractDespite advances in elucidating the genetic epidemiology of Alzheimer's disease and frontotemporal dementia, the aetiology for most patients with dementia remains unclear. We examined the genetic epidemiology of dementia in a recent genetically isolated Dutch population founded around

  9. Understanding social dysfunction in the behavioural variant of frontotemporal dementia: the role of emotion and sarcasm processing.

    Science.gov (United States)

    Kipps, C M; Nestor, P J; Acosta-Cabronero, J; Arnold, R; Hodges, J R

    2009-03-01

    Social interaction is profoundly affected in the behavioural form of frontotemporal dementia (bvFTD) yet there are few means of objectively assessing this. Diagnosis of bvFTD is based on informant report, however a number of individuals with a clinical profile consistent with the disease have no imaging abnormality and seem to remain stable, with doubt about the presence of underlying neurodegenerative pathology. We aimed to quantify aspects of the behavioural disorder and link it to the underlying level of atrophy in socially relevant brain regions. We tested individuals with either bvFTD (N = 26) or Alzheimer's disease (N = 9) and 16 controls using The Awareness of Social Inference Test (TASIT) to assess their ability to identify emotion and sarcasm in video vignettes. A subset of bvFTD patients (N = 21) and controls (N = 12) were scanned using MRI within 6 months of assessment. There was marked impairment in the ability of bvFTD patients whose scans showed abnormalities to recognize sarcastic, but not sincere statements. Their capacity to interpret negative emotion was also impaired, and this appeared to be a major factor underlying the deficit in sarcasm recognition. Clinically diagnosed bvFTD patients whose scans were normal, Alzheimer's disease patients and controls had no difficulty in appreciating both types of statement. In a multivariate imaging analysis it was shown that the sarcasm (and emotion recognition) deficit was dependent on a circuit involving the lateral orbitofrontal cortex, insula, amygdala and temporal pole, particularly on the right. Performance on a more global test of cognitive function, the Addenbrooke's Cognitive Examination did not have a unique association with these regions. The TASIT is an objective test of social dysfunction in bvFTD which indexes the frontotemporal volume loss in bvFTD patients and provides an objective measure for separating behavioural patients who are likely to decline from those who may remain stable. These

  10. One Size Does Not Fit All: Face Emotion Processing Impairments in Semantic Dementia, Behavioural-Variant Frontotemporal Dementia and Alzheimer’s Disease Are Mediated by Distinct Cognitive Deficits

    Directory of Open Access Journals (Sweden)

    Laurie A. Miller

    2012-01-01

    Full Text Available Patients with frontotemporal dementia (both behavioural variant [bvFTD] and semantic dementia [SD] as well as those with Alzheimer's disease (AD show deficits on tests of face emotion processing, yet the mechanisms underlying these deficits have rarely been explored. We compared groups of patients with bvFTD (n = 17, SD (n = 12 or AD (n = 20 to an age- and education-matched group of healthy control subjects (n = 36 on three face emotion processing tasks (Ekman 60, Emotion Matching and Emotion Selection and found that all three patient groups were similarly impaired. Analyses of covariance employed to partial out the influences of language and perceptual impairments, which frequently co-occur in these patients, provided evidence of different underlying cognitive mechanisms. These analyses revealed that language impairments explained the original poor scores obtained by the SD patients on the Ekman 60 and Emotion Selection tasks, which involve verbal labels. Perceptual deficits contributed to Emotion Matching performance in the bvFTD and AD patients. Importantly, all groups remained impaired on one task or more following these analyses, denoting a primary emotion processing disturbance in these dementia syndromes. These findings highlight the multifactorial nature of emotion processing deficits in patients with dementia.

  11. Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum

    Science.gov (United States)

    Shahheydari, Hamideh; Ragagnin, Audrey; Walker, Adam K.; Toth, Reka P.; Vidal, Marta; Jagaraj, Cyril J.; Perri, Emma R.; Konopka, Anna; Sultana, Jessica M.; Atkin, Julie D.

    2017-01-01

    Protein homeostasis, or proteostasis, has an important regulatory role in cellular function. Protein quality control mechanisms, including protein folding and protein degradation processes, have a crucial function in post-mitotic neurons. Cellular protein quality control relies on multiple strategies, including molecular chaperones, autophagy, the ubiquitin proteasome system, endoplasmic reticulum (ER)-associated degradation (ERAD) and the formation of stress granules (SGs), to regulate proteostasis. Neurodegenerative diseases are characterized by the presence of misfolded protein aggregates, implying that protein quality control mechanisms are dysfunctional in these conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that are now recognized to overlap clinically and pathologically, forming a continuous disease spectrum. In this review article, we detail the evidence for dysregulation of protein quality control mechanisms across the whole ALS-FTD continuum, by discussing the major proteins implicated in ALS and/or FTD. We also discuss possible ways in which protein quality mechanisms could be targeted therapeutically in these disorders and highlight promising protein quality control-based therapeutics for clinical trials. PMID:28539871

  12. Clinical and biological phenotypes of frontotemporal dementia: Perspectives for disease modifying therapies.

    Science.gov (United States)

    Gazzina, S; Manes, M A; Padovani, A; Borroni, B

    2017-06-01

    Frontotemporal Dementia (FTD) is a progressive neurodegenerative condition which encompasses a group of clinically, neuropathologically and genetically heterogeneous disorders characterized by selective involvement of the frontal and temporal lobes. FTD is characterized by changes in behaviour and personality, frontal executive deficits and language dysfunction. Different phenotypes have been defined on the basis of presenting clinical symptoms, behavioural variants of FTD (bvFTD) and primary progressive aphasia (PPA), which includes nonfluent/agrammatic variant PPA (avPPA) and semantic variant PPA (svPPA). These presentations can overlap with atypical parkinsonian disorders (i.e., corticobasal syndrome, progressive supranuclear palsy) and amyotrophic lateral sclerosis. Each syndrome can be associated with one or more neuropathological hallmark, and in some cases it may be due to autosomal inherited disorder caused by mutations in a number of genes. Currently, there is no specific treatment available to prevent disease progression. FTD treatment is based on symptomatic management, and most therapies lack quality evidence from randomized, placebo-controlled clinical trials. Recent advances in the understanding of FTD pathophysiology and genetics have led to the development of potentially disease-modifying therapies. In this review, we discussed current knowledge and recommendations with regards to symptomatic and disease-modifying therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Olfactory deficits in frontotemporal dementia as measured by the Alberta Smell Test.

    Science.gov (United States)

    Heyanka, Daniel J; Golden, Charles J; McCue, Robert B; Scarisbrick, David M; Linck, John F; Zlatkin, Nancy I

    2014-01-01

    The study of olfaction in neurodegeneration has primarily focused on Alzheimer's disease. Research of olfaction in frontotemporal dementia (FTD) has generally not been empirically studied. The current study compared olfaction in FTD to major depressive disorder (MDD) using the Alberta Smell Test (AST). Independent-samples t test results suggested olfaction in FTD was impaired when compared with participants diagnosed with MDD. The AST Total score (out of 20 trials) significantly predicted the diagnostic group and accounted for 40% of the variance in diagnostic group status with an odds ratio of 20.08. Results suggested that a cutoff of ≤2/20 differentiated FTD from MDD with 94% accuracy (91% sensitivity, 97% specificity) and a cutoff of ≤1/20 differentiated the groups with a 95.5% hit rate (91% sensitivity, 100% specificity). Results confirmed olfactory identification deficits in FTD and suggested that the AST is an effective tool for the demarcation of FTD from MDD. This is especially important due to the potential for significant overlap in the behavioral/emotional phenotype and cognitive deficits between the two disorders when presented with early stages of FTD.

  14. Measuring and modifying abnormal social cognition in frontal variant frontotemporal dementia.

    Science.gov (United States)

    Lough, Sinclair; Hodges, John R

    2002-08-01

    We describe a 57-year-old man (MW) with frontal variant frontotemporal dementia (fv-FTD) who presented with a long history of drinking problem and marital disharmony followed by gradual changes in personality with disinhibition, stereotypic checking, overeating and a decline in self-care. Structural MRI imaging confirmed marked frontal atrophy involving particularly the ventromedial region. Performance on standard tests of frontal executive function was largely unremarkable and MW obtained a perfect score on the Mini-Mental State Examination (MMSE). In contrast, an experimental battery of tasks designed to evaluate theory of mind (ToM) revealed marked deficits. MW's challenging and disruptive behaviours, notably obsessive checking of car suspension by rocking, and wandering, responded to behavioural modification regimes adapted from the neurorehabilitation literature. In conclusion, deficits in ToM may underline the gross abnormalities in social conduct, which characterise fv-FTD; ToM appears to dissociate from frontal executive function; and behavioural modification approaches can be of benefit in this disorder.

  15. Impaired recognition of body expressions in the behavioral variant of frontotemporal dementia.

    Science.gov (United States)

    Van den Stock, Jan; De Winter, François-Laurent; de Gelder, Beatrice; Rangarajan, Janaki Raman; Cypers, Gert; Maes, Frederik; Sunaert, Stefan; Goffin, Karolien; Vandenberghe, Rik; Vandenbulcke, Mathieu

    2015-08-01

    Progressive deterioration of social cognition and emotion processing are core symptoms of the behavioral variant of frontotemporal dementia (bvFTD). Here we investigate whether bvFTD is also associated with impaired recognition of static (Experiment 1) and dynamic (Experiment 2) bodily expressions. In addition, we compared body expression processing with processing of static (Experiment 3) and dynamic (Experiment 4) facial expressions, as well as with face identity processing (Experiment 5). The results reveal that bvFTD is associated with impaired recognition of static and dynamic bodily and facial expressions, while identity processing was intact. No differential impairments were observed regarding motion (static vs. dynamic) or category (body vs. face). Within the bvFTD group, we observed a significant partial correlation between body and face expression recognition, when controlling for performance on the identity task. Voxel-Based Morphometry (VBM) analysis revealed that body emotion recognition was positively associated with gray matter volume in a region of the inferior frontal gyrus (pars orbitalis/triangularis). The results are in line with a supramodal emotion recognition deficit in bvFTD.

  16. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia.

    Science.gov (United States)

    Freischmidt, Axel; Wieland, Thomas; Richter, Benjamin; Ruf, Wolfgang; Schaeffer, Veronique; Müller, Kathrin; Marroquin, Nicolai; Nordin, Frida; Hübers, Annemarie; Weydt, Patrick; Pinto, Susana; Press, Rayomond; Millecamps, Stéphanie; Molko, Nicolas; Bernard, Emilien; Desnuelle, Claude; Soriani, Marie-Hélène; Dorst, Johannes; Graf, Elisabeth; Nordström, Ulrika; Feiler, Marisa S; Putz, Stefan; Boeckers, Tobias M; Meyer, Thomas; Winkler, Andrea S; Winkelman, Juliane; de Carvalho, Mamede; Thal, Dietmar R; Otto, Markus; Brännström, Thomas; Volk, Alexander E; Kursula, Petri; Danzer, Karin M; Lichtner, Peter; Dikic, Ivan; Meitinger, Thomas; Ludolph, Albert C; Strom, Tim M; Andersen, Peter M; Weishaupt, Jochen H

    2015-05-01

    Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.

  17. TDP-43 in the hypoglossal nucleus identifies amyotrophic lateral sclerosis in behavioral variant frontotemporal dementia.

    Science.gov (United States)

    Halliday, Glenda M; Kiernan, Matthew C; Kril, Jillian J; Mito, Remika; Masuda-Suzukake, Masami; Hasegawa, Masato; McCann, Heather; Bartley, Lauren; Dobson-Stone, Carol; Kwok, John B J; Hornberger, Michael; Hodges, John R; Tan, Rachel H

    2016-07-15

    The hypoglossal nucleus was recently identified as a key brain region in which the presence of TDP-43 pathology could accurately discriminate TDP-43 proteinopathy cases with clinical amyotrophic lateral sclerosis (ALS). The objective of the present study was to assess the hypoglossal nucleus in behavioral variant frontotemporal dementia (bvFTD), and determine whether TDP-43 in this region is associated with clinical ALS. Twenty-nine cases with neuropathological FTLD-TDP and clinical bvFTD that had not been previously assessed for hypoglossal TDP-43 pathology were included in this study. Of these 29 cases, 41% (n=12) had a dual diagnosis of bvFTD-ALS at presentation, all 100% (n=12) of which demonstrated hypoglossal TDP-43 pathology. Of the 59% (n=17) cohort that presented with pure bvFTD, 35% (n=6) were identified with hypoglossal TDP-43 pathology. Review of the case files of all pure bvFTD cases revealed evidence of possible or probable ALS in 5 of the 6 hypoglossal-positive cases (83%) towards the end of disease, and this was absent from all cases without such pathology. In conclusion, the present study validates grading the presence of TDP-43 in the hypoglossal nucleus for the pathological identification of bvFTD cases with clinical ALS, and extends this to include the identification of cases with possible ALS at end-stage.

  18. Restoration of Progranulin Expression Rescues Cortical Neuron Generation in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia

    Directory of Open Access Journals (Sweden)

    Susanna Raitano

    2015-01-01

    Full Text Available To understand how haploinsufficiency of progranulin (PGRN causes frontotemporal dementia (FTD, we created induced pluripotent stem cells (iPSCs from patients carrying the GRNIVS1+5G > C mutation (FTD-iPSCs. FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD. Although generation of neuroprogenitors was unaffected, their further differentiation into CTIP2-, FOXP2-, or TBR1-TUJ1 double-positive cortical neurons, but not motorneurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of GRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNA sequencing analysis confirmed reversal of the altered gene expression profile following genetic correction. We identified the Wnt signaling pathway as one of the top defective pathways in FTD-iPSC-derived neurons, which was reversed following genetic correction. Differentiation of FTD-iPSCs in the presence of a WNT inhibitor mitigated defective corticogenesis. Therefore, we demonstrate that PGRN haploinsufficiency hampers corticogenesis in vitro.

  19. Astrocyte pathology in a human neural stem cell model of frontotemporal dementia caused by mutant TAU protein

    Science.gov (United States)

    Hallmann, Anna-Lena; Araúzo-Bravo, Marcos J.; Mavrommatis, Lampros; Ehrlich, Marc; Röpke, Albrecht; Brockhaus, Johannes; Missler, Markus; Sterneckert, Jared; Schöler, Hans R.; Kuhlmann, Tanja; Zaehres, Holm; Hargus, Gunnar

    2017-01-01

    Astroglial pathology is seen in various neurodegenerative diseases including frontotemporal dementia (FTD), which can be caused by mutations in the gene encoding the microtubule-associated protein TAU (MAPT). Here, we applied a stem cell model of FTD to examine if FTD astrocytes carry an intrinsic propensity to degeneration and to determine if they can induce non-cell-autonomous effects in neighboring neurons. We utilized CRISPR/Cas9 genome editing in human induced pluripotent stem (iPS) cell-derived neural progenitor cells (NPCs) to repair the FTD-associated N279K MAPT mutation. While astrocytic differentiation was not impaired in FTD NPCs derived from one patient carrying the N279K MAPT mutation, FTD astrocytes appeared larger, expressed increased levels of 4R-TAU isoforms, demonstrated increased vulnerability to oxidative stress and elevated protein ubiquitination and exhibited disease-associated changes in transcriptome profiles when compared to astrocytes derived from one control individual and to the isogenic control. Interestingly, co-culture experiments with FTD astrocytes revealed increased oxidative stress and robust changes in whole genome expression in previously healthy neurons. Our study highlights the utility of iPS cell-derived NPCs to elucidate the role of astrocytes in the pathogenesis of FTD. PMID:28256506

  20. Inclusion body myopathy, Paget's disease of the bone and fronto-temporal dementia: a disorder of autophagy.

    Science.gov (United States)

    Ju, Jeong-Sun; Weihl, Conrad C

    2010-04-15

    Inclusion body myopathy associated with Paget's disease of the bone and fronto-temporal dementia (IBMPFD) is a progressive autosomal dominant disorder caused by mutations in p97/VCP (valosin-containing protein). p97/VCP is a member of the AAA+ (ATPase associated with a variety of activities) protein family and participates in multiple cellular processes. One particularly important role for p97/VCP is facilitating intracellular protein degradation. p97/VCP has traditionally been thought to mediate the ubiquitin-proteasome degradation of proteins; however, recent studies challenge this dogma. p97/VCP clearly participates in the degradation of aggregate-prone proteins, a process principally mediated by autophagy. In addition, IBMPFD mutations in p97/VCP lead to accumulation of autophagic structures in patient and transgenic animal tissue. This is likely due to a defect in p97/VCP-mediated autophagosome maturation. The following review will discuss the evidence for p97/VCP in autophagy and how a disruption in this process contributes to IBMPFD pathogenesis.

  1. Conceptualizing neuropsychiatric diseases with multimodal data-driven meta-analyses – The case of behavioral variant frontotemporal dementia

    Science.gov (United States)

    Schroeter, Matthias L.; Laird, Angela R.; Chwiesko, Caroline; Deuschl, Christine; Schneider, Else; Bzdok, Danilo; Eickhoff, Simon B.; Neumann, Jane

    2014-01-01

    Introduction Uniform coordinate systems in neuroimaging research have enabled comprehensive systematic and quantitative meta-analyses. Such approaches are particularly relevant for neuropsychiatric diseases, the understanding of their symptoms, prediction and treatment. Behavioral variant frontotemporal dementia (bvFTD), a common neurodegenerative syndrome, is characterized by deep alterations in behavior and personality. Investigating this ‘nexopathy’ elucidates the healthy social and emotional brain. Methods Here, we combine three multimodal meta-analyses approaches – anatomical & activation likelihood estimates and behavioral domain profiles – to identify neural correlates of bvFTD in 417 patients and 406 control subjects and to extract mental functions associated with this disease by meta-analyzing functional activation studies in the comprehensive probabilistic functional brain atlas of the BrainMap database. Results The analyses identify the frontomedian cortex, basal ganglia, anterior insulae and thalamus as most relevant hubs, with a regional dissociation between atrophy and hypometabolism. Neural networks affected by bvFTD were associated with emotion and reward processing, empathy and executive functions (mainly inhibition), suggesting these functions as core domains affected by the disease and finally leading to its clinical symptoms. In contrast, changes in theory of mind or mentalizing abilities seem to be secondary phenomena of executive dysfunctions. Conclusions The study creates a novel conceptual framework to understand neuropsychiatric diseases by powerful data-driven meta-analytic approaches that shall be extended to the whole neuropsychiatric spectrum in the future. PMID:24763126

  2. Proteomic study of frontotemporal dementia%额颞叶痴呆的蛋白质组研究

    Institute of Scientific and Technical Information of China (English)

    彭立威; 杨国锋; 纪建国; 王鲁宁

    2011-01-01

    目的 为深入理解额颞叶痴呆分子机制并寻找诊断治疗该疾病的蛋白质标记物,选取5例经病理证实的额颞叶痴呆患者与4例无神经系统疾病老年人尸检脑标本进行蛋白质组学研究.方法 死亡24 h内新鲜取材的尸检额叶、颞叶蛋白质以固相pH梯度等电聚焦为第一向,SDS-PAGE垂直电泳为第二向进行双向电泳(2-DE),图象分析软件Imagemaster 2D Elite分析电泳图谱,MALDI-TOF质谱或MALDI-TOF/TOF串联质谱鉴定蛋白质.结果 18种蛋白质的表达量在额颢叶痴呆患者与正常老年人显著不同.12个在额颞叶痴呆表达量上调的蛋白质被鉴定为3-磷酸甘油醛脱氢酶、尿嘧啶DNA糖苷水解酶、Cu-Zn超氧化物歧化酶、异柠檬酸脱氢酶亚单位、synaptotagmin I、Peroxiredoxin2、胶质纤维酸性蛋白、P25 alpha、烯酰辅酶A水合酶短链1、吡哆醇-5′-磁酸氧化酶、Mn超氧化物歧化酶、α-烯醇化酶;6个在额颞叶痴呆表达量下调的蛋白质被鉴定为抗氧化蛋白2(酸性钙离子依赖型磷脂酶A)、铁蛋白H链、谷氨酸脱氢酶、肽基脯氨酸顺反异构酶A、血清白蛋白前体、二氢嘧啶酶相关蛋白2.结论 额颞叶痴呆患者脑组织中神绛纤维缠结相关蛋白、氧应激蛋白、凋亡相关蛋白及重要代谢酶的表达发生变化,有助于深入理解额颞叶痴呆分子机制并有望在额颞叶痴呆的早期诊断及新药开发上发挥作用.%Objective To investigate molecular mechanisms of frontotemporal dementia (FTD). Methods Comparative proteomic analysis of brain proteins was employed to study 5 frontotemporal dementia patients compared to 4 controls. The brains of subjects who died without clinical or pathological involvement of nervous system and brains of frontotemporal dementia patients were obtained at autopsy. The brain proteins extracted with mixture of urea, CHAPS, DTT. IPG buffer and protease inhibitors were run immobilized pH gradient (IPG

  3. Differential neuropsychological patterns of frontal variant frontotemporal dementia and Alzheimer's disease in a study of diagnostic concordance.

    Science.gov (United States)

    Giovagnoli, Anna R; Erbetta, Alessandra; Reati, Fabiola; Bugiani, Orso

    2008-04-01

    Although the pathological hallmarks of Alzheimer's disease (AD) and frontal variant frontotemporal dementia (fvFTD) predict different cognitive patterns, many comparative neuropsychological studies showed no difference in the expected cognitive domains. Inconsistencies in diagnostic criteria, small cohorts of patients, and neuropsychological assessment may account for such findings. Moreover, discrepancies in memory and executive dysfunctions that are expected to distinguish AD and fvFTD may reflect the basic brain organization. Adhering to a strict concordance of clinical and neuroradiological criteria, we compared many patients with AD and fvFTD using a large neuropsychological battery. One hundred and thirty-nine patients with AD (n=89) or fvFTD (n=50) were retrospectively considered in order to verify the diagnostic congruence of clinical and neuroradiological aspects. On this basis, 117 patients with AD (n=77) or fvFTD (n=40) with similar duration and severity of dementia were selected. Ninety-one healthy subjects were also controlled. Mean scores in tests for abstract reasoning, planning, set shifting, initiative, verbal fluency, immediate and episodic memory, constructive, ideomotor and orofacial praxis, selective and divided attention, visuomotor coordination, and visual perception were evaluated. Separate analyses of variance and post hoc Bonferroni tests showed that, with respect to controls, both patient groups were significantly impaired in all neuropsychological tests. Compared to fvFTD patients, AD patients were significantly impaired in episodic memory, selective attention, visual perception, visuomotor coordination, and constructive praxis, whereas no differences were found in executive, intellective, and linguistic abilities between the two patient groups. Logistic regression analyses revealed that episodic memory significantly predicted the diagnosis of AD while no executive deficit was able to predict the diagnosis of fvFTD. To conclude, memory

  4. Brain reserve capacity in frontotemporal dementia: a voxel-based {sup 18}F-FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Perneczky, Robert; Diehl-Schmid, Janine; Kurz, Alexander [Technische Universitaet Muenchen, Klinik und Poliklinik fuer Psychiatrie und Psychotherapie, Muenchen (Germany); Drzezga, Alexander [Technische Universitaet Muenchen, Nuklearmedizinische Klinik, Muenchen (Germany)

    2007-07-15

    The association of the regional cerebral metabolic rate of glucose utilisation (rCMRglc) and years of schooling has been extensively studied in Alzheimer's disease (AD). The results suggest that brain reserve capacity (BRC) allows patients with more years of schooling to cope better with AD pathology. The objective of this study was to provide initial evidence for BRC in frontotemporal dementia (FTD). Twenty-nine patients with FTD and 16 healthy age- and education-matched controls underwent PET imaging of the brain with {sup 18}F-fluoro-2-deoxy-glucose. A group comparison of rCMRglc was conducted between patients and controls and the output was saved as region of interest (ROI). A linear regression analysis with education as the independent and rCMRglc as the dependent variable, adjusted for age, gender and total score on the CERAD neuropsychological battery, was conducted in SPM2 over the pre-assigned ROI. Patients showed a reduced rCMRglc in almost the entire prefrontal cortex and the anterior cingulate cortex as compared with controls (p < 0.05 corrected for multiple comparisons). The regression analysis revealed a significant negative association between years of schooling and rCMRglc in the bilateral inferior frontal cortex (p < 0.001, uncorrected for multiple comparisons), which was independent of demographic variables and cognitive performance level. There was a strong negative correlation of rCMRglc and education (r = -0.45). The study provides initial evidence for BRC in FTD. The findings suggest that interindividual differences in educational level affect BRC by partially mediating the relationship between neurodegeneration and the clinical manifestation of FTD. (orig.)

  5. Neurodegenerative disease phenotypes in carriers of MAPT p.A152T, a risk factor for frontotemporal dementia spectrum disorders and Alzheimer disease.

    Science.gov (United States)

    Lee, Suzee E; Tartaglia, Maria C; Yener, Görsev; Genç, Sermin; Seeley, William W; Sanchez-Juan, Pascual; Moreno, Fermin; Mendez, Mario F; Klein, Eric; Rademakers, Rosa; López de Munain, Adolfo; Combarros, Onofre; Kramer, Joel H; Kenet, Robert O; Boxer, Adam L; Geschwind, Michael D; Gorno-Tempini, Maria-Luisa; Karydas, Anna M; Rabinovici, Gil D; Coppola, Giovanni; Geschwind, Daniel H; Miller, Bruce L

    2013-01-01

    Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.

  6. Neuronal loss in familial frontotemporal dementia with ubiquitin-positive, tau-negative inclusions.

    Science.gov (United States)

    Cairns, N J; Brännström, T; Khan, M N; Rossor, M N; Lantos, P L

    2003-06-01

    The neuronal density in the frontal, temporal, and parietal lobes was determined in nine cases of familial frontotemporal dementia with ubiquitin-positive, tau-negative inclusions (FTDU). The mean age at onset was 56.9 +/- 2.2 years and the duration of disease was 6.7 +/- 0.5 years. The mean age at death was 63.6 +/- 2.2 years. There was substantial loss (34%) of brain weight (877 +/- 73 g) in the familial cases in comparison with 10 normal aged controls (1326 +/- 50 g, P tau-negative intracytoplasmic and intranuclear inclusions and dystrophic neurites in varying sites and numbers. Neuronal loss was estimated in nine cases of familial FTDU and in 10 aged controls using a stereological probe, the optical "disector," and a computerized stereology system (CAST-Grid, Olympus, Denmark). There was a significant reduction in neuronal density in the frontal lobe (22.3 +/- 3.8 x 10(3)/mm(3)) of familial FTDU in comparison to aged controls (33.1 +/- 1.7 x 10(3) per mm(3), P estimate of the relative numbers of neurons was calculated by multiplying the numerical density by the cortical thickness, which showed a striking loss of neurons of 56% in the frontal lobe, 52% loss in the temporal lobe, and a 49% loss in the parietal lobe of familial FTDU when compared to controls. This study shows that familial FTDU has profound focal neuronal loss in multiple association areas that relate to the clinical symptoms characteristic of the disease.

  7. Dissociation of Structural and Functional Integrities of the Motor System in Amyotrophic Lateral Sclerosis and Behavioral-Variant Frontotemporal Dementia

    Science.gov (United States)

    Bae, Jong Seok; Ferguson, Michele; Tan, Rachel; Mioshi, Eneida; Simon, Neil; Burrell, James; Vucic, Steve; Hodges, John R.; Kiernan, Matthew C

    2016-01-01

    Background and Purpose This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). Methods Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. Results The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. Conclusions Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders. PMID:26932257

  8. Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

    Energy Technology Data Exchange (ETDEWEB)

    Verfaillie, Sander C.J.; Adriaanse, Sofie M.; Binnewijzend, Maja A.A.; Benedictus, Marije R.; Ossenkoppele, Rik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Wattjes, Mike P.; Lammertsma, Adriaan A.; Boellaard, Ronald; Berckel, Bart N.M. van; Barkhof, Frederik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Pijnenburg, Yolande A.L.; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Centre, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Kuijer, Joost P.A. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2015-10-15

    Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [{sup 18}F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68). Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET. (orig.)

  9. Physical aggression among patients with dementia, neuropathologically confirmed post-mortem.

    Science.gov (United States)

    Liljegren, Madeleine; Landqvist Waldö, Maria; Englund, Elisabet

    2017-08-31

    To investigate the prevalence of physical aggression among patients with dementia of different types and to analyze potential differences in clinical traits, in terms of singular or repetitive behavior and occurrence in early or late stage of the disease. We also aimed at examining against whom the physical aggression was exerted. We included 281 cases with a neuropathological dementia diagnosis from the brain bank at the Department of Pathology, Lund University, for this retrospective medical records review. The study covers cases with a post-mortem examination performed between 1967 and 2013. Of the 281 patients studied, 97 (35%) patients had a history of exerting physical aggression during the course of their disease. The patients with frontotemporal dementia exerted physical aggression earlier in the course of their disease than Alzheimer's disease patients. The most frequent victims of the patients' physical aggression were health staff and other patients. The aggression also affected family members as well as (to the demented patient) unknown people. The frequency of the physical aggression differed among the different diagnostic groups; frontotemporal dementia patients exhibiting a higher physical aggression frequency score than did Alzheimer's disease patients. The patterns of manifested physical aggression thus differ between the frontotemporal dementia and Alzheimer's disease patient groups in this study. Knowledge about such differences may be of value in decision making in patient care. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Kraepelin’s description of chronic mania: a clinical picture that meets the behavioral variant frontotemporal dementia phenotype

    Directory of Open Access Journals (Sweden)

    Leandro Boson Gambogi

    Full Text Available ABSTRACT Chronic mania is an under-investigated condition and few reports have associated this disorder with an organic background. The present work examines Kraepelin’s reliable description of chronic mania from a current behavioral neurology viewpoint. Kraepelin had described a cluster of symptoms that are now recognized as core manifestations of the behavioral variant frontotemporal dementia (bvFTD clinical phenotype. We also carried out additional reviews of original manuscripts from Kraepelin’s peers, in order to find any case reports that might fulfill the current diagnostic proposal for bvFTD. Even though we failed to find an ideal case, we found some scholars who seemed to agree that chronic mania should be considered a special form of dementia. The present work highlights, through historical data, the possible overlapping features between primary psychiatric disorders and neuropsychiatric symptoms secondary to neurodegenerative conditions.

  11. Alzheimer Disease and Behavioral Variant Frontotemporal Dementia: Automatic Classification Based on Cortical Atrophy for Single-Subject Diagnosis.

    Science.gov (United States)

    Möller, Christiane; Pijnenburg, Yolande A L; van der Flier, Wiesje M; Versteeg, Adriaan; Tijms, Betty; de Munck, Jan C; Hafkemeijer, Anne; Rombouts, Serge A R B; van der Grond, Jeroen; van Swieten, John; Dopper, Elise; Scheltens, Philip; Barkhof, Frederik; Vrenken, Hugo; Wink, Alle Meije

    2016-06-01

    Purpose To investigate the diagnostic accuracy of an image-based classifier to distinguish between Alzheimer disease (AD) and behavioral variant frontotemporal dementia (bvFTD) in individual patients by using gray matter (GM) density maps computed from standard T1-weighted structural images obtained with multiple imagers and with independent training and prediction data. Materials and Methods The local institutional review board approved the study. Eighty-four patients with AD, 51 patients with bvFTD, and 94 control subjects were divided into independent training (n = 115) and prediction (n = 114) sets with identical diagnosis and imager type distributions. Training of a support vector machine (SVM) classifier used diagnostic status and GM density maps and produced voxelwise discrimination maps. Discriminant function analysis was used to estimate suitability of the extracted weights for single-subject classification in the prediction set. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were calculated for image-based classifiers and neuropsychological z scores. Results Training accuracy of the SVM was 85% for patients with AD versus control subjects, 72% for patients with bvFTD versus control subjects, and 79% for patients with AD versus patients with bvFTD (P ≤ .029). Single-subject diagnosis in the prediction set when using the discrimination maps yielded accuracies of 88% for patients with AD versus control subjects, 85% for patients with bvFTD versus control subjects, and 82% for patients with AD versus patients with bvFTD, with a good to excellent AUC (range, 0.81-0.95; P ≤ .001). Machine learning-based categorization of AD versus bvFTD based on GM density maps outperforms classification based on neuropsychological test results. Conclusion The SVM can be used in single-subject discrimination and can help the clinician arrive at a diagnosis. The SVM can be used to distinguish disease-specific GM patterns in patients with AD

  12. Robotherapy with Dementia Patients

    Directory of Open Access Journals (Sweden)

    Francisco Martín

    2013-01-01

    Full Text Available Humanoids have increasingly become the focus of attention in robotics research in recent years, especially in service and personal assistance robotics. This paper presents the application developed for humanoid robots in the therapy of dementia patients as a cognitive stimulation tool. The behaviour of the robot during the therapy sessions is visually programmed in a session script that allows music to play, physical movements (dancing, exercises, etc., speech synthesis and interaction with the human monitor. The application includes the control software on board the robot and some tools like the visual script generator or a monitor to supervise the robot behaviour during the sessions. The robot application's impact on the patient's health has been studied. Experiments with real patients have been performed in collaboration with a centre of research in neurodegenerative diseases. Initial results show a slight or mild improvement in neuropsychiatric symptoms over other traditional therapy methods.

  13. Robotherapy with Dementia Patients

    Directory of Open Access Journals (Sweden)

    Francisco Martín

    2013-01-01

    Full Text Available Humanoids have increasingly become the focus of attention in robotics research in recent years, especially in service and personal assistance robotics. This paper presents the application developed for humanoid robots in the therapy of dementia patients as a cognitive stimulation tool. The behaviour of the robot during the therapy sessions is visually programmed in a session script that allows music to play, physical movements (dancing, exercises, etc., speech synthesis and interaction with the human monitor. The application includes the control software on board the robot and some tools like the visual script generator or a monitor to supervise the robot behaviour during the sessions. The robot applicationʹs impact on the patientʹs health has been studied. Experiments with real patients have been performed in collaboration with a centre of research in neurodegenerative diseases. Initial results show a slight or mild improvement in neuropsychiatric symptoms over other traditional therapy methods.

  14. Self-Awareness and Self-Monitoring of Cognitive and Behavioral Deficits in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia and Probable Alzheimer's Disease

    Science.gov (United States)

    Banks, Sarah; Weintraub, Sandra

    2008-01-01

    Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight.…

  15. High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands

    NARCIS (Netherlands)

    P. Rizzu (Patrizia); M. Hillebrand; R. Ravid (Rivka); B.A. Oostra (Ben); C.M. van Duijn (Cock); M. Goedert; J.C. van Swieten (John); M. Joosse (Marijke); M. Hasegawa (Masato); M. Stevens (Martijn); A. Tibben (Arend); M.F. Niermeijer (Martinus); P. Heutink (Peter)

    1999-01-01

    textabstractMutations in microtubule-associated protein tau recently have been identified in familial cases of frontotemporal dementia (FTD). We report the frequency of tau mutations in a large population-based study of FTD carried out in the Netherlands from January 1994 to June 1

  16. Psychiatric Presentation of Frontotemporal Dementia Associated with Inclusion Body Myopathy due to the VCP Mutation (R155H in a French Family

    Directory of Open Access Journals (Sweden)

    Agnès Jacquin

    2013-10-01

    Full Text Available Introduction: Inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD is a rare late-onset autosomal dominant disorder due to a mutation of the valosin-containing protein (VCP gene. Case Report: We report the case of a patient who developed progressive weakness of the limbs in his fifties, until he was confined to a wheelchair. At that time, he developed acute behavioural changes including irritability, severe anxiety and major depression, which led to him being hospitalised in a psychiatric hospital. He also suffered from aphasia and executive function impairment, which helped us to diagnose a behavioural form of frontotemporal dementia (FTD. The diagnosis of IBMPFD due to a mutation in the VCP gene was confirmed by a genetic study of the VCP gene (R155H mutation. Discussion: The clinical diagnosis of IBMPFD is suggested by the presence of at least one of three major manifestations as follows: inclusion body myopathy (mean onset at 42 years of age, Paget's disease of the bone and FTD (mean onset at 55 years of age. It is mostly the behavioural form of FTD (behavioural changes, executive dysfunction and aphasia. One interesting finding in our report is the predominance of the psychiatric symptoms at the beginning of the behavioural changes, which led to the diagnosis of FTD. The diagnosis of IBMPFD was confirmed by the genetic study: the R155H mutation found on exon 5 domain CDC48 is the most frequent of the 18 known mutations in the VCP gene.

  17. Self-Awareness and Self-Monitoring of Cognitive and Behavioral Deficits in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia and Probable Alzheimer’s Disease

    Science.gov (United States)

    Banks, Sarah; Weintraub, Sandra

    2008-01-01

    Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight. Different components of insight, self-awareness and self-monitoring, are also often considered separate phenomena. The current study compared insight in patients with PPA, bvFTD, and probable Alzheimer’s disease (PrAD) and a group of cognitively intact control subjects. Additionally, differences in insight for the domains primarily affected by the three types of dementia, namely, Behavior, Naming, and Memory, were assessed, and self-awareness and self-monitoring were compared. A total of 55 participants were enrolled. Participants were asked to complete self-estimate scales demonstrating their perceived ability immediately prior to, and immediately following a test in each domain of interest. Results indicated that PPA and normal control groups performed very similarly on control (Weight and Eyesight) and cognitive domains, whereas bvFTD and PrAD patients were unable to accurately assess Memory. All three diagnostic groups failed to accurately assess their behavioral symptoms, suggesting that this domain is vulnerable to loss of insight across diagnoses. Naming ability, in contrast, was either accurately assessed or underestimated in all groups. Finally, there were no notable differences between self-awareness and self-monitoring, potential explanations for this are examined. PMID:18194832

  18. Family caregivers of individuals with frontotemporal dementia: examining the relationship between coping and caregiver physical and mental health.

    Science.gov (United States)

    Wong, Cindy C; Wallhagen, Margaret I

    2014-01-01

    To identify strategies to assist family caregivers of individuals with frontotemporal dementia (FTD) in dealing with their caregiving demands, nurses must understand these family members' unique needs and how they currently deal with their demands. The purpose of this study was to examine the relationship between coping and caregiver physical and mental health among FTD family caregivers. Participants were primary caregivers of individuals with FTD (with behavioral symptoms) living at home (N = 61). A small positive association was noted between problem-focused coping and caregiver physical health (r = 0.29, p caregiver mental health (r = 0.21, p = 0.10). However, multiple regression analysis showed that emotion-focused coping (β = 0.46, p caregiver mental health and explained approximately 14% of its variance. These findings support the potential value of emotion-focused coping strategies when dealing with behavioral symptoms manifested by individuals with FTD.

  19. Sortilin-Mediated Endocytosis Determines Levels of the Fronto-Temporal Dementia Protein, Progranulin

    DEFF Research Database (Denmark)

    Hu, Fenghua; Padukkavidana, Thihan; Vægter, Christian Bjerggaard;

    2010-01-01

    The most common inherited form of Fronto-Temporal Lobar Degeneration (FTLD) known stems from Progranulin (GRN) mutation, and exhibits TDP-43 plus ubiquitin protein aggregates in brain. Despite the causative role of GRN haploinsufficiency in FTLD-TDP, the neurobiology of this secreted glycoprotein...

  20. 额颞痴呆的神经病理及分子遗传学研究进展%Recent advances in neuropathology and molecular genetics of frontotemporal dementia

    Institute of Scientific and Technical Information of China (English)

    刘功禄; 赵永波

    2010-01-01

    @@ 额颞痴呆(frontotemporal dementia,FTD)或额颞叶变性(frontotemporal lobardegeneration,FTLD)是一组以进行性行为异常、人格改变、语言障碍,而早期记忆相对保留为特征的临床综合征.

  1. What is known about the subjective needs of people with behavioural variant frontotemporal dementia? A scoping review.

    Science.gov (United States)

    Dinand, Claudia; Nover, Sabine Ursula; Holle, Daniela; Zischka, Matthias; Halek, Margareta

    2016-07-01

    Behavioural variant frontotemporal dementia (bvFTD) is an early-onset and progressive neurodegenerative disease associated with strong changes in judgement, behaviour, personality and emotions. These changes can cause significant problems in everyday life for people with bvFTD and their families, and have implications for health and society. Currently, there are no suitable evidence-based specific interventions for people with bvFTD. This scoping review aims to identify the self-expressed needs, demands and coping strategies of people with bvFTD. Identifying these issues is the first step towards the development of need-based psycho-social interventions for people with bvFTD. A comprehensive literature research was conducted of German and English scientific articles published between January 2000 and October 2014 using the databases MEDLINE, CINAHL, PsycINFO, PSYNDEX, SocINDEX, GeroLit, the Cochrane Library, ProQuest, the German National Library and additional search strategies in terms of a scoping review. Articles were identified by combining search terms related to 'frontotemporal dementia' with terms related to 'self-expressions', 'needs/demands' and 'coping'. After excluding duplicates, two independent reviewers screened the titles and abstracts of 2317 records for eligibility. Because eligibility could not be assessed from the titles or abstracts of 28 articles, those articles were assessed using the full text. One poster abstract met our research question and a few articles were related, but no article met all of the inclusion criteria. This lack of scientifically based knowledge concerning the perspective of people with bvFTD is discussed with reference to the search strategy and the research questions, disease-related aspects such as changes in behaviour or language and emotions and the difficulties in researching this topic. Recommendations are formulated for future research considering the perspective of people with bvFTD and that will involve the

  2. Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis

    Energy Technology Data Exchange (ETDEWEB)

    Valotassiou, V; Tsougos, I; Tzavara, C; Georgoulias, P [Nuclear Medicine Dpt, University Hospital of Larissa, Larissa (Greece); Papatriantafyllou, J; Karageorgiou, C [Neurology Dpt, General Hospital ' G. Gennimatas' , Athens (Greece); Sifakis, N; Zerva, C [Nuclear Medicine Dpt, ' Alexandra' University Hospital, Athens (Greece)], E-mail: vanvalot@yahoo.gr

    2009-05-15

    Introduction. Brain perfusion studies with single-photon emission computed tomography (SPECT) have been applied in demented patients to provide better discrimination between frontotemporal dementia (FTD) and Alzheimer's disease (AD). Aim. To assess the perfusion of specific Brodmann (Br) areas of the brain cortex in FTD and AD patients, using NeuroGam processing program to provide 3D voxel-by-voxel cerebral SPECT analysis. Material and methods. We studied 34 consecutive patients. We used the established criteria for the diagnosis of dementia and the specific established criteria for the diagnosis of FTD and AD. All the patients had a neuropsychological evaluation with a battery of tests including the mini-mental state examination (MMSE).Twenty-six patients (16 males, 10 females, mean age 68.76{+-}6.51 years, education 11.81{+-}4.25 years, MMSE 16.69{+-}9.89) received the diagnosis of FTD and 8 patients (all females, mean age 71.25{+-}10.48 years, education 10{+-}4.6 years, MMSE 12.5{+-}3.89) the diagnosis of AD. All the patients underwent a brain SPECT. We applied the NeuroGam Software for the evaluation of brain perfusion in specific Br areas in the left (L) and right (R) hemispheres. Results. Statistically significant hypoperfusion in FTD compared to AD patients, was found in the following Br areas: 11L (p<0.0001), 11R, 20L, 20R, 32L, 38L, 38R, 44L (p<0.001), 32R, 36L, 36R, 45L, 45R, 47R (p<0.01), 9L, 21L, 39R, 44R, 46R, 47L (p<0.05). On the contrary, AD patients presented significant (p<0.05) hypoperfusion in 7R and 39R Br areas. Conclusion. NeuroGam processing program of brain perfusion SPECT could result in enhanced accuracy for the differential diagnosis between AD and FTD patients.

  3. Communication of brain network core connections altered in behavioral variant frontotemporal dementia but possibly preserved in early-onset Alzheimer's disease

    Science.gov (United States)

    Daianu, Madelaine; Jahanshad, Neda; Mendez, Mario F.; Bartzokis, George; Jimenez, Elvira E.; Thompson, Paul M.

    2015-03-01

    Diffusion imaging and brain connectivity analyses can assess white matter deterioration in the brain, revealing the underlying patterns of how brain structure declines. Fiber tractography methods can infer neural pathways and connectivity patterns, yielding sensitive mathematical metrics of network integrity. Here, we analyzed 1.5-Tesla wholebrain diffusion-weighted images from 64 participants - 15 patients with behavioral variant frontotemporal dementia (bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly controls. Using whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We evaluated the brain's networks focusing on the most highly central and connected regions, also known as hubs, in each diagnostic group - specifically the "high-cost" structural backbone used in global and regional communication. The high-cost backbone of the brain, predicted by fiber density and minimally short pathways between brain regions, accounted for 81-92% of the overall brain communication metric in all diagnostic groups. Furthermore, we found that the set of pathways interconnecting high-cost and high-capacity regions of the brain's communication network are globally and regionally altered in bvFTD, compared to healthy participants; however, the overall organization of the high-cost and high-capacity networks were relatively preserved in EOAD participants, relative to controls. Disruption of the major central hubs that transfer information between brain regions may impair neural communication and functional integrity in characteristic ways typical of each subtype of dementia.

  4. Semi-quantitative analysis of perfusion of Brodmann areas in the differential diagnosis of cognitive impairment in Alzheimer's disease, fronto-temporal dementia and mild cognitive impairment.

    Science.gov (United States)

    Tranfaglia, Cristina; Palumbo, Barbara; Siepi, Donatella; Sinzinger, Helmut; Parnetti, Lucilla

    2009-01-01

    Different perfusion defects reflect neurological damage characteristics of different kinds of dementia. Our aim was to investigate the role of brain single photon emission tomography (SPET) with semiquantitative analysis of Brodmann areas in dementia, by technetium-99m - hexamethyl-propylenamine- oxime ((99m)Tc-HMPAO) brain SPET with semiquantitative analysis of Brodmann areas in patients with Alzheimer's disease (AD), frontotemporal dementia (FTD) and mild cognitive impairment (MCI). We studied 75 patients, 25 with AD (NiNCDS ADRDA criteria), 25 with FTD (Lund and Manchester criteria), 25 with MCI (EADC criteria). After i.v. injection of 740MBq of (99m)Tc-HMPAO, each patient underwent brain SPET. A software application was used able to map the SPET brain image to a stereotaxic atlas (Talairach), providing an affine co-registration by blocks of data defined in the Talairach space. A normal database calculating voxel by voxel the mean and the standard deviation of the measured values was built. Functional SPET data of 3D regions of interest (ROI) of predefined Brodmann's area templates were compared with those of a database of healthy subjects of the same age and gender. Mean values obtained in the Brodmann area ROI in the different groups of patients studied were evaluated. Our results showed that different Brodmann areas were significantly impaired in the different categories of dementia subjects. Both areas 37 (temporal gyrus) and 39 (angular gyrus) of AD patients (mean+/-SD: 37L= -1.6+/-1.0; 37R= -1.5+/-1.1; 39L= -2.3+/-1.3; 39R= -1.9+/-1.2) showed significant hypoperfusion (Pareas 40 (supramarginal gyrus) (40L= -2.6+/-1.0; 40R= -2.3+/-1.1) with respect to MCI patients (40L= -1.8+/-0.9; 40R= -1.7+/-1.2). Finally, FTD patients showed significant hypoperfusion (Pareas 47 (frontal association cortex) (47L= -1.8+/-0.8; 47R= -1.1+/-0.8) in comparison with MCI subjects (47L= -1.2+/-0.9; 47R= -0.9+/-0.9). In conclusion, our results suggest that semiquantitative

  5. Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis

    Science.gov (United States)

    Valotassiou, V.; Papatriantafyllou, J.; Sifakis, N.; Karageorgiou, C.; Tsougos, I.; Tzavara, C.; Zerva, C.; Georgoulias, P.

    2009-05-01

    Introduction. Brain perfusion studies with single-photon emission computed tomography (SPECT) have been applied in demented patients to provide better discrimination between frontotemporal dementia (FTD) and Alzheimer's disease (AD). Aim. To assess the perfusion of specific Brodmann (Br) areas of the brain cortex in FTD and AD patients, using NeuroGam processing program to provide 3D voxel-by-voxel cerebral SPECT analysis. Material and methods. We studied 34 consecutive patients. We used the established criteria for the diagnosis of dementia and the specific established criteria for the diagnosis of FTD and AD. All the patients had a neuropsychological evaluation with a battery of tests including the mini-mental state examination (MMSE).Twenty-six patients (16 males, 10 females, mean age 68.76±6.51 years, education 11.81±4.25 years, MMSE 16.69±9.89) received the diagnosis of FTD and 8 patients (all females, mean age 71.25±10.48 years, education 10±4.6 years, MMSE 12.5±3.89) the diagnosis of AD. All the patients underwent a brain SPECT. We applied the NeuroGam Software for the evaluation of brain perfusion in specific Br areas in the left (L) and right (R) hemispheres. Results. Statistically significant hypoperfusion in FTD compared to AD patients, was found in the following Br areas: 11L (pareas. Conclusion. NeuroGam processing program of brain perfusion SPECT could result in enhanced accuracy for the differential diagnosis between AD and FTD patients.

  6. Comparison of grey matter and metabolic reductions in frontotemporal dementia using FDG-PET and voxel-based morphometric MR studies

    Energy Technology Data Exchange (ETDEWEB)

    Kanda, Tomonori; Uemura, Takafumi; Miyamoto, Naokazu; Yoshikawa, Toshiki; Kono, Atsushi K. [Hyogo Brain and Heart Center, Department of Radiology and Nuclear Medicine, Himeji, Hyogo (Japan); Ishii, Kazunari [Hyogo Brain and Heart Center, Department of Radiology and Nuclear Medicine, Himeji, Hyogo (Japan); Hyogo Institute for Aging Brain and Cognitive Disorders, Division of Neuroimaging Research, Himeji, Hyogo (Japan); Mori, Etsuro [Hyogo Institute for Aging Brain and Cognitive Disorders, Division of Clinical Neurosciences, Himeji, Hyogo (Japan); Tohoku University Graduate School of Medicine, Behavioral Neurology and Cognitive Neuroscience, Sendai, Miyagi (Japan)

    2008-12-15

    The aim of this study was to investigate the regional differences between the morphologic and functional changes in the same patients with frontotemporal dementia (FTD) using statistical parametric mapping and voxel-based morphometry (VBM). Thirteen FTD patients (mean age, 64.9 years old; mean MMSE score, 17.7), 20 sex-matched Alzheimer's disease (AD) patients (mean age, 65.0 years old; mean MMSE score, 17.5), and 20 normal volunteers (mean age, 65.2 years old; mean MMSE score, 29.0) underwent both [{sup 18}F]FDG positron emission tomography and three-dimensional spoiled gradient echo MRI. Statistical parametric mapping was used to conduct a VBM analysis of the morphologic data, which were compared voxel by voxel with the results of a similar analysis of glucose metabolic data. FTD patients showed decreased grey matter volume and decreased glucose metabolism in the frontal lobe and anterior temporal lobe. In addition, there was a clear asymmetry in grey matter volume in FTD patients by the VBM analysis while the glucose metabolic data showed little asymmetry. In AD patients, glucose metabolic reduction occurred in the bilateral posterior cingulate gyri and parietal lobules while grey matter density decreased the least in the same patients. In FTD, metabolic and morphologic changes occur in the bilateral frontal lobe and temporal lobe with a limited asymmetry whereas there was considerable discordance in the AD group. (orig.)

  7. A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic, and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts.

    Science.gov (United States)

    Ingre, Caroline; Landers, John E; Rizik, Naji; Volk, Alexander E; Akimoto, Chizuru; Birve, Anna; Hübers, Annemarie; Keagle, Pamela J; Piotrowska, Katarzyna; Press, Rayomand; Andersen, Peter Munch; Ludolph, Albert C; Weishaupt, Jochen H

    2013-06-01

    Profilin 1 is a central regulator of actin dynamics. Mutations in the gene profilin 1 (PFN1) have very recently been shown to be the cause of a subgroup of amyotrophic lateral sclerosis (ALS). Here, we performed a large screen of US, Nordic, and German familial and sporadic ALS and frontotemporal dementia (FTLD) patients for PFN1 mutations to get further insight into the spectrum and pathogenic relevance of this gene for the complete ALS/FTLD continuum. Four hundred twelve familial and 260 sporadic ALS cases and 16 ALS/FTLD cases from Germany, the Nordic countries, and the United States were screened for PFN1 mutations. Phenotypes of patients carrying PFN1 mutations were studied. In a German ALS family we identified the novel heterozygous PFN1 mutation p.Thr109Met, which was absent in controls. This novel mutation abrogates a phosphorylation site in profilin 1. The recently described p.Gln117Gly sequence variant was found in another familial ALS patient from the United States. The ALS patients with mutations in PFN1 displayed spinal onset motor neuron disease without overt cognitive involvement. PFN1 mutations were absent in patients with motor neuron disease and dementia, and in patients with only FTLD. We provide further evidence that PFN1 mutations can cause ALS as a Mendelian dominant trait. Patients carrying PFN1 mutations reported so far represent the "classic" ALS end of the ALS-FTLD spectrum. The novel p.Thr109Met mutation provides additional proof-of-principle that mutant proteins involved in the regulation of cytoskeletal dynamics can cause motor neuron degeneration. Moreover, this new mutation suggests that fine-tuning of actin polymerization by phosphorylation of profilin 1 might be necessary for motor neuron survival.

  8. Performance of patients with frontotemporal lobar degeneration on artistic tasks: A pilot study

    Directory of Open Access Journals (Sweden)

    Maria Cristina Anauate

    Full Text Available ABSTRACT Several studies have addressed visuospatial and executive skills in artistic activities in Frontotemporal Lobar Degeneration (FTLD and Alzheimer's disease (AD. Objective: To investigate the performance of FTLD patients compared to controls on two artistic tasks. Methods: Four FTLD patients with mean age of 57 (8.7 years and schooling of 12.2 (4.5 years plus 10 controls with mean age of 62.9 (8.6 years and schooling of 12.3 (4.6 years, were assessed using the Lowenstein Occupational Therapy Cognitive Assessment (LOTCA and by a three-stage artistic protocol including visual observation, copying and collage, based on a Sisley painting. Results: FTLD patients had lower scores than controls on Visuospatial Perception, Copy, Collage, Examiner's Observation, and Total, showing distinct patterns of performance according to FTLD sub-type: semantic PPA, nonfluent PPA and bvFTD. Conclusion: FTLD patients presented impairment in the visuospatial and executive skills required to perform artistic tasks. We demonstrated that the application of the instrument as a complimentary method for assessing cognitive skills in this group of patients is possible. Further studies addressing larger and more homogeneous samples of FTLD patients as well as other dementias are warranted.

  9. The CERAD Neuropsychological Battery in Patients with Frontotemporal Lobar Degeneration

    Directory of Open Access Journals (Sweden)

    Ramona M. Haanpää

    2015-04-01

    Full Text Available Background/Aims: The diagnosis of frontotemporal lobar degeneration (FTLD is based on neuropsychological examination in addition to clinical symptoms and brain imaging. There is no simple, validated, cognitive tool available in screening for FTLD. The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NB was originally devised to identify the early cognitive changes related to Alzheimer's disease (AD. Our aim was to investigate the utility of the CERAD-NB in FTLD. Methods: Patients with FTLD (n = 95 and AD (n = 90 were assessed with the CERAD-NB, Trail Making Test parts A and B and single-letter Phonemic Fluency. Results: FTLD patients were more severely impaired in the Verbal Fluency subtest in the CERAD-NB and Trail Making Test part A compared to AD patients. In addition, AD patients were more impaired in memory subtests compared to FTLD patients. Conclusion: The CERAD-NB may be a useful tool in screening for FTLD. Impaired performance in Verbal Fluency with moderately well-preserved Delayed Recall and Memory Tests may help in identifying patients with probable FTLD and discriminating FTLD from AD. Adding the Trail Making Test to the battery might enhance its value as a screening instrument for FTLD.

  10. Drug Utilization Pattern in Patients with Different Types of Dementia in Western India

    Directory of Open Access Journals (Sweden)

    Mansi Patel

    2014-01-01

    Full Text Available Background. Dementia is one of the most frequent disorders among elderly patients, reaching to epidemic proportions with an estimated 4.6 million new cases globally annually. Partially effective treatments are available for dementia. Aims & Objectives. We aim to study drugs used in dementia and find out frequency of types of Dementia. Method. This was an observational study conducted at rurally based tertiary care hospital. Prospective data was collected from outpatient department, while retrospective data was collected from medical records. Descriptive statistics were used to analyze data. Result. Total 125 prescriptions of patients diagnosed with dementia were analyzed. Alzheimer’s dementia was most common (65.6%, followed by vascular dementia (21.6%, and frontotemporal dementia (10.4%, with the rarest being Lewy body dementia in (2.4% cases. 60.57% of patients were males. Mini Mental Score Examination mean score was 15.93 ± 1.37. Frontal Battery Assessment mean score was 4.75 ± 1.01. Prescribed drugs were Donepezil (68.49%, Rivastigmine (13.63%, Donepezil + Memantine (6.43% and Galantamine (12.83%, Quetiapine (38.46%, Lorazepam (23.07%, Clozapine (11.53%, Escitalopram (10.25%, Haloperidol (3.84%, Zolpidem, Sertraline, Olanzepine (2.56%, Nitrazepine, Lamotrigine, Fluoxetine, Tianeptine (1.28%, Folic acid, and Vitamin B12, respectively. Conclusion. Alzheimer’s is the most common type of dementia while Donepezil was the most frequent drug.

  11. Recognition of facial expressions of different emotional intensities in patients with frontotemporal lobar degeneration

    NARCIS (Netherlands)

    Kessels, Roy P. C.; Gerritsen, Lotte; Montagne, Barbara; Ackl, Nibal; Diehl, Janine; Danek, Adrian

    2007-01-01

    Behavioural problems are a key feature of frontotemporal lobar degeneration (FTLD). Also, FTLD patients show impairments in emotion processing. Specifically, the perception of negative emotional facial expressions is affected. Generally, however, negative emotional expressions are regarded as more d

  12. Clinical, genetic and neuropathological features of frontotemporal dementia: an update and guide.

    Science.gov (United States)

    Pelicano Paulos, Jorge; Massano, João

    2013-01-01

    Introdução: A Degenerescência Lobar Frontotemporal engloba um conjunto de situações heterogéneas que partilham sintomas cognitivos e comportamentais, bem como características patológicas macroscópicas. As bases genéticas e características histopatológicas são bastante diversas e formam a base da classificação molecular das várias doenças, sendo difícil fazer uma correlação com os achados clínicos e síndromas. A investigação científica trouxe um conjunto vasto de conhecimentos, nem sempre fáceis de acompanhar,especialmente nos últimos anos em relação à genética e histopatologia.Material e Métodos: Os autores fizeram uma pesquisa de literatura neste tema, escolheram referências relevantes, extraíram e sistematizaram os dados.Resultados e Conclusão: o texto apresenta uma revisão atualizada dos aspetos clínicos, genéticos e histopatológicos da Degenerescência Lobar Frontotemporal, com ênfase especial na Demência Frontotemporal, a doença mais comum. O tratamento é também revisto e são propostas pelos autores estratégias relativamente à escolha dos testes genéticos na prática clínica. Deveriam serpromovidos a atenção e conhecimento públicos sobre este grupo de doenças.

  13. MMP-9 and MMP-2 Contribute to Neuronal Cell Death in iPSC Models of Frontotemporal Dementia with MAPT Mutations

    Directory of Open Access Journals (Sweden)

    Md Helal U. Biswas

    2016-09-01

    Full Text Available How mutations in the microtubule-associated protein tau (MAPT gene cause frontotemporal dementia (FTD remains poorly understood. We generated and characterized multiple induced pluripotent stem cell (iPSC lines from patients with MAPT IVS10+16 and tau-A152T mutations and a control subject. In cortical neurons differentiated from these and other published iPSC lines, we found that MAPT mutations do not affect neuronal differentiation but increase the 4R/3R tau ratio. Patient neurons had significantly higher levels of MMP-9 and MMP-2 and were more sensitive to stress-induced cell death. Inhibitors of MMP-9/MMP-2 protected patient neurons from stress-induced cell death and recombinant MMP-9/MMP-2 were sufficient to decrease neuronal survival. In tau-A152T neurons, inhibition of the ERK pathway decreased MMP-9 expression. Moreover, ectopic expression of 4R but not 3R tau-A152T in HEK293 cells increased MMP-9 expression and ERK phosphorylation. These findings provide insights into the molecular pathogenesis of FTD and suggest a potential therapeutic target for FTD with MAPT mutations.

  14. Voxel-based comparison of rCBF SPET images in frontotemporal dementia and Alzheimer's disease highlights the involvement of different cortical networks

    Energy Technology Data Exchange (ETDEWEB)

    Varrone, Andrea; Pappata, Sabina; Quarantelli, Mario; Alfano, Bruno [Biostructure and Bioimaging Institute, National Research Council, Via S. Pansini 5, 80131 Napoli (Italy); Caraco, Corradina [Institute of Experimental Medicine and Biotechnology, Piano Lago Mangone (Cosenza) (Italy); Soricelli, Andrea [Faculty of Motor Sciences, University ' ' Parthenope' ' , Napoli (Italy); Milan, Graziella; Postiglione, Alfredo [Department of Clinical and Experimental Medicine, University ' ' Federico II' ' of Napoli (Italy); Salvatore, Marco [Department of Biomorphological and Functional Sciences, University ' ' Federico II' ' of Napoli (Italy)

    2002-11-01

    Characteristic patterns of regional cerebral blood flow (rCBF) reduction, as detected by technetium-99m hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO) single-photon emission tomography (SPET), may help clinicians in differentiating patients with frontotemporal dementia (FTD) from those with Alzheimer's disease (AD). However, in some cases these patients may share common rCBF abnormalities and the visual analysis and/or the region of interest (ROI) approach may not sensitively detect more localised focal changes that could be more specific for each pathology. Recently, automated voxel-by-voxel statistical analysis of perfusion brain maps has been applied to SPET images. This method has the advantage of including the rCBF information for the whole brain for statistical analysis without any a priori hypothesis regarding the regions possibly involved. This could result in a better characterisation of rCBF differences in brain regions while also reducing the operator's subjectivity and the time required for data analysis. The purpose of this study was to apply such a technique to highlight the specific brain areas showing a relative functional involvement in FTD and AD. Thus, we compared the relative rCBF patterns obtained in eight FTD patients with those obtained in 21 AD patients using {sup 99m}Tc-HMPAO SPET and statistical parametric mapping (SPM). When FTD patients were compared with AD patients, relatively lower rCBF was observed in right medial frontal cortex (BA 8, 9, 10), right anterior cingulate cortex (BA 32), right temporal cortex (BA 21/22), right orbitofrontal cortex (BA 11) and ventrolateral prefrontal cortex (BA 47); in BA 47 the reduction was evident bilaterally but was more marked on the right side. On the other hand, when AD patients were compared with FTD patients, a significant relative rCBF decrease was found in the bilateral superior parietal cortex (BA 7); this decrease was more extensive on the left side, where it also included the

  15. Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia.

    Science.gov (United States)

    Skillbäck, Tobias; Farahmand, Bahman Y; Rosén, Christoffer; Mattsson, Niklas; Nägga, Katarina; Kilander, Lena; Religa, Dorota; Wimo, Anders; Winblad, Bengt; Schott, Jonathan M; Blennow, Kaj; Eriksdotter, Maria; Zetterberg, Henrik

    2015-09-01

    Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-β1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-β1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-β1-42 and amyloid-β1-42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-β1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-β1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with

  16. An analysis of communication in conversation in patients with dementia.

    Science.gov (United States)

    Rousseaux, Marc; Sève, Amandine; Vallet, Marion; Pasquier, Florence; Mackowiak-Cordoliani, Marie Anne

    2010-11-01

    Patients with degenerative dementia often show language disorders, but little is known about their verbal (VC) and non-verbal communication (NVC). Our aim was to analyse VC and NVC in patients with standard criteria of mild-moderately severe dementia (MMSE ≥14/30) resulting from Alzheimer's disease (AD; 29 cases), behavioural variant of frontotemporal dementia (FTD; 16), or dementia with Lewy bodies (DLB; 13). We used the Lille Communication Test, which addresses three domains: participation in communication (PC: greeting, attention, participation), VC (verbal comprehension, speech outflow, intelligibility, word production, syntax, verbal pragmatics and verbal feedback), and NVC (understanding gestures, affective expressivity, producing gestures, pragmatics and feedback). Patients were compared with 47 matching control subjects. AD patients were partially impaired (p≤0.01) in PC (greeting), and more definitely in VC, especially by verbal comprehension and word finding difficulties and to a much lesser degree in verbal pragmatics (responding to open questions, presenting new information), while NVC was mostly preserved. FTD patients were severely impaired in PC. VC difficulties were related to lexical-semantic, syntactic and more specifically pragmatic problems. NVC was impaired by difficulties in affective expressivity, pragmatics and feedback management. DLB patients showed modest difficulties with VC. PC, VC and NVC strongly correlated with performance in the dementia rating scale. In conclusion, the profile of communication difficulties was quite different between groups. FTD patients showed most severe difficulties in PC and verbal and non-verbal pragmatics, in relation to their frontal lesions. AD patients had prominent impairment of lexical-semantic operations.

  17. The influence of singing on social engagement for persons with severe frontotemporal dementia

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    2010-01-01

    Panksepp (2010) describes how the pain of social loss opens the gateway to depression, and how the chronic sense of aloneness pervades many mental health illnesses and pathologies. In relation to this, psychological and behavioural symptoms of neurodegenerative diseases like dementia are reported...... and behavioural symptoms of dementia. Based on evidence from clinical research (Ridder 2003; Ridder, Wigram & Ottesen 2009) the method of intervention utilises the musical and communicative aspects of therapeutic singing in order to focus attention, retrieve memory, regulate arousal and engage in social...

  18. Psychological Impact of Predictive Genetic Testing in VCP Inclusion Body Myopathy, Paget Disease of Bone and Frontotemporal Dementia.

    Science.gov (United States)

    Surampalli, Abhilasha; Khare, Manaswitha; Kubrussi, Georgette; Wencel, Marie; Tanaja, Jasmin; Donkervoort, Sandra; Osann, Kathryn; Simon, Mariella; Wallace, Douglas; Smith, Charles; M McInerney-Leo, Aideen; Kimonis, Virginia

    2015-10-01

    Inclusion Body Myopathy associated with Paget's disease of bone and Fronto-temporal Dementia, also known as multisystem proteinopathy is an autosomal dominant, late onset neurodegenerative disorder caused by mutations in Valosin containing protein (VCP) gene. This study aimed to assess uptake and decision making for predictive genetic testing and the impact on psychological well-being. Individuals who had participated in the gene discovery study with a 50 % a priori risk of inheriting VCP disease were sent a letter of invitation offering genetic counseling and testing and were also invited to participate in this psychosocial study. A total of 102 individuals received an invitation and 33 individuals participated in genetic counseling and testing (32.3 %) with 29 completing baseline questionnaires. Twenty completed the follow-up post-test Hospital Anxiety and Depression Scale questionnaire including 13 of the 18 who had tested positive. Mean risk perception at baseline was 50.1 %. Reasons for testing included planning for the future, relieving uncertainty, informing children and satisfying curiosity. At baseline, one quarter of the participants had high levels of anxiety. However, scores were normal one year following testing. In this small cohort, one third of individuals at 50 % risk chose pre-symptomatic testing. Although one quarter of those choosing testing had high anxiety at baseline, this was not evident at follow-up.

  19. A Comparison of Magnetic Resonance Imaging and Neuropsychological Examination in the Diagnostic Distinction of Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

    Science.gov (United States)

    Wang, Jingjing; Redmond, Stephen J; Bertoux, Maxime; Hodges, John R; Hornberger, Michael

    2016-01-01

    The clinical distinction between Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) remains challenging and largely dependent on the experience of the clinician. This study investigates whether objective machine learning algorithms using supportive neuroimaging and neuropsychological clinical features can aid the distinction between both diseases. Retrospective neuroimaging and neuropsychological data of 166 participants (54 AD; 55 bvFTD; 57 healthy controls) was analyzed via a Naïve Bayes classification model. A subgroup of patients (n = 22) had pathologically-confirmed diagnoses. Results show that a combination of gray matter atrophy and neuropsychological features allowed a correct classification of 61.47% of cases at clinical presentation. More importantly, there was a clear dissociation between imaging and neuropsychological features, with the latter having the greater diagnostic accuracy (respectively 51.38 vs. 62.39%). These findings indicate that, at presentation, machine learning classification of bvFTD and AD is mostly based on cognitive and not imaging features. This clearly highlights the urgent need to develop better biomarkers for both diseases, but also emphasizes the value of machine learning in determining the predictive diagnostic features in neurodegeneration.

  20. The influence of singing on social engagement for persons with severe frontotemporal dementia

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    2010-01-01

    Panksepp (2010) describes how the pain of social loss opens the gateway to depression, and how the chronic sense of aloneness pervades many mental health illnesses and pathologies. In relation to this, psychological and behavioural symptoms of neurodegenerative diseases like dementia are reported...... functioning (e.g. the lost ability to process language, to focus attention, to remember and to act in what is defined as a socially appropriate manner) makes it very challenging to engage in social interaction, especially in groups. Music therapy is applied as a non-pharmacological treatment of psychological...... and behavioural symptoms of dementia. Based on evidence from clinical research (Ridder 2003; Ridder, Wigram & Ottesen 2009) the method of intervention utilises the musical and communicative aspects of therapeutic singing in order to focus attention, retrieve memory, regulate arousal and engage in social...

  1. Evidence of semantic processing impairments in behavioural variant frontotemporal dementia and Parkinson's disease.

    Science.gov (United States)

    Cousins, Katheryn A Q; Grossman, Murray

    2017-09-13

    Category-specific impairments caused by brain damage can provide important insights into how semantic concepts are organized in the brain. Recent research has demonstrated that disease to sensory and motor cortices can impair perceptual feature knowledge important to the representation of semantic concepts. This evidence supports the grounded cognition theory of semantics, the view that lexical knowledge is partially grounded in perceptual experience and that sensory and motor regions support semantic representations. Less well understood, however, is how heteromodal semantic hubs work to integrate and process semantic information. Although the majority of semantic research to date has focused on how sensory cortical areas are important for the representation of semantic features, new research explores how semantic memory is affected by neurodegeneration in regions important for semantic processing. Here, we review studies that demonstrate impairments to abstract noun knowledge in behavioural variant frontotemporal degeneration (bvFTD) and to action verb knowledge in Parkinson's disease, and discuss how these deficits relate to disease of the semantic selection network. Findings demonstrate that semantic selection processes are supported by the left inferior frontal gyrus (LIFG) and basal ganglia, and that disease to these regions in bvFTD and Parkinson's disease can lead to categorical impairments for abstract nouns and action verbs, respectively.

  2. Anatomical Correlates of Non-Verbal Perception in Dementia Patients

    Directory of Open Access Journals (Sweden)

    Pin-Hsuan Lin

    2016-08-01

    Full Text Available Purpose: Patients with dementia who have dissociations in verbal and non-verbal sound processing may offer insights into the anatomic basis for highly related auditory modes. Methods: To determine the neuronal networks on non-verbal perception, 16 patients with Alzheimer’s dementia (AD, 15 with behavior variant fronto-temporal dementia (bv-FTD, 14 with semantic dementia (SD were evaluated and compared with 15 age-matched controls. Neuropsychological and auditory perceptive tasks were included to test the ability to compare pitch changes, scale-violated melody and for naming and associating with environmental sound. The brain 3D T1 images were acquired and voxel-based morphometry (VBM was used to compare and correlated the volumetric measures with task scores. Results: The SD group scored the lowest among 3 groups in pitch or scale-violated melody tasks. In the environmental sound test, the SD group also showed impairment in naming and also in associating sound with pictures. The AD and bv-FTD groups, compared with the controls, showed no differences in all tests. VBM with task score correlation showed that atrophy in the right supra-marginal and superior temporal gyri was strongly related to deficits in detecting violated scales, while atrophy in the bilateral anterior temporal poles and left medial temporal structures was related to deficits in environmental sound recognition. Conclusions: Auditory perception of pitch, scale-violated melody or environmental sound reflects anatomical degeneration in dementia patients and the processing of non-verbal sounds is mediated by distinct neural circuits.

  3. Anatomical Correlates of Non-Verbal Perception in Dementia Patients

    Science.gov (United States)

    Lin, Pin-Hsuan; Chen, Hsiu-Hui; Chen, Nai-Ching; Chang, Wen-Neng; Huang, Chi-Wei; Chang, Ya-Ting; Hsu, Shih-Wei; Hsu, Che-Wei; Chang, Chiung-Chih

    2016-01-01

    Purpose: Patients with dementia who have dissociations in verbal and non-verbal sound processing may offer insights into the anatomic basis for highly related auditory modes. Methods: To determine the neuronal networks on non-verbal perception, 16 patients with Alzheimer’s dementia (AD), 15 with behavior variant fronto-temporal dementia (bv-FTD), 14 with semantic dementia (SD) were evaluated and compared with 15 age-matched controls. Neuropsychological and auditory perceptive tasks were included to test the ability to compare pitch changes, scale-violated melody and for naming and associating with environmental sound. The brain 3D T1 images were acquired and voxel-based morphometry (VBM) was used to compare and correlated the volumetric measures with task scores. Results: The SD group scored the lowest among 3 groups in pitch or scale-violated melody tasks. In the environmental sound test, the SD group also showed impairment in naming and also in associating sound with pictures. The AD and bv-FTD groups, compared with the controls, showed no differences in all tests. VBM with task score correlation showed that atrophy in the right supra-marginal and superior temporal gyri was strongly related to deficits in detecting violated scales, while atrophy in the bilateral anterior temporal poles and left medial temporal structures was related to deficits in environmental sound recognition. Conclusions: Auditory perception of pitch, scale-violated melody or environmental sound reflects anatomical degeneration in dementia patients and the processing of non-verbal sounds are mediated by distinct neural circuits. PMID:27630558

  4. Genotype-specific differences between mouse CNS stem cell lines expressing frontotemporal dementia mutant or wild type human tau.

    Directory of Open Access Journals (Sweden)

    Miranda E Orr

    Full Text Available Stem cell (SC lines that capture the genetics of disease susceptibility provide new research tools. To assess the utility of mouse central nervous system (CNS SC-containing neurosphere cultures for studying heritable neurodegenerative disease, we compared neurosphere cultures from transgenic mice that express human tau with the P301L familial frontotemporal dementia (FTD mutation, rTg(tau(P301L4510, with those expressing comparable levels of wild type human tau, rTg(tau(wt21221. rTg(tau(P301L4510 mice express the human tau(P301L variant in their forebrains and display cellular, histological, biochemical and behavioral abnormalities similar to those in human FTD, including age-dependent differences in tau phosphorylation that distinguish them from rTg(tau(wt21221 mice. We compared FTD-hallmark tau phosphorylation in neurospheres from rTg(tau(P301L4510 mice and from rTg(tau(wt21221 mice. The tau genotype-specific phosphorylation patterns in neurospheres mimicked those seen in mice, validating use of neurosphere cultures as models for studying tau phosphorylation. Genotype-specific tau phosphorylation was observed in 35 independent cell lines from individual fetuses; tau in rTg(tau(P301L4510 cultures was hypophosphorylated in comparison with rTg(tau(wt21221 as was seen in young adult mice. In addition, there were fewer human tau-expressing cells in rTg(tau(P301L4510 than in rTg(tau(wt21221 cultures. Following differentiation, neuronal filopodia-spine density was slightly greater in rTg(tau(P301L4510 than rTg(tau(wt21221 and control cultures. Together with the recapitulation of genotype-specific phosphorylation patterns, the observation that neurosphere lines maintained their cell line-specific-differences and retained SC characteristics over several passages supports the utility of SC cultures as surrogates for analysis of cellular disease mechanisms.

  5. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer’s and Parkinson’s diseases

    Science.gov (United States)

    Ferrari, Raffaele; Wang, Yunpeng; Vandrovcova, Jana; Guelfi, Sebastian; Witeolar, Aree; Karch, Celeste M; Schork, Andrew J; Fan, Chun C; Brewer, James B; Schellenberg, Gerard S; Dillon, William P; Sugrue, Leo P; Hess, Christopher P; Yokoyama, Jennifer S; Bonham, Luke W; Rabinovici, Gil D; Miller, Bruce L; Andreassen, Ole A; Dale, Anders M; Hardy, John; Desikan, Rahul S

    2016-01-01

    Background Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer’s disease (AD) and Parkinson’s disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap between FTD, AD and PD to assess shared pathobiology and identify novel genetic variants associated with increased risk for FTD. Methods Summary statistics were obtained from the International FTD Genomics Consortium, International PD Genetics Consortium and International Genomics of AD Project (n>75 000 cases and controls). We used conjunction false discovery rate (FDR) to evaluate genetic pleiotropy and conditional FDR to identify novel FTD-associated SNPs. Relevant variants were further evaluated for expression quantitative loci. Results We observed SNPs within the HLA, MAPT and APOE regions jointly contributing to increased risk for FTD and AD or PD. By conditioning on polymorphisms associated with PD and AD, we found 11 loci associated with increased risk for FTD. Meta-analysis across two independent FTD cohorts revealed a genome-wide signal within the APOE region (rs6857, 3′-UTR=PVRL2, p=2.21×10−12), and a suggestive signal for rs1358071 within the MAPT region (intronic=CRHR1, p=4.91×10−7) with the effect allele tagging the H1 haplotype. Pleiotropic SNPs at the HLA and MAPT loci associated with expression changes in cis-genes supporting involvement of intracellular vesicular trafficking, immune response and endo/lysosomal processes. Conclusions Our findings demonstrate genetic pleiotropy in these neurodegenerative diseases and indicate that sporadic FTD is a polygenic disorder where multiple pleiotropic loci with small effects contribute to increased disease risk. PMID:27899424

  6. The emerging roles of microRNAs in the pathogenesis of frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum disorders.

    Science.gov (United States)

    Gascon, Eduardo; Gao, Fen-Biao

    2014-01-01

    Increasing evidence suggests that frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) share some clinical, pathological, and molecular features as part of a common neurodegenerative spectrum disorder. In recent years, enormous progress has been made in identifying both pathological proteins and genetic mutations associated with FTD-ALS. However, the molecular pathogenic mechanisms of disease onset and progression remain largely unknown. Recent studies have uncovered unexpected links between FTD-ALS and multiple aspects of RNA metabolism, setting the stage for further understanding of the disorder. Here, the authors will focus on microRNAs and review the emerging roles of these small RNAs in several aspects of FTD-ALS pathogenesis.

  7. CSF neurofilament proteins in the differential diagnosis of dementia

    NARCIS (Netherlands)

    de Jong, D; Jansen, R W M M; Pijnenburg, Y A L; van Geel, W J A; Borm, G F; Kremer, Berry; Verbeek, M.

    BACKGROUND: Neurofilament (NF) proteins are major cytoskeletal constituents of neurons. Increased CSF NF levels may reflect neuronal degeneration. OBJECTIVE: To investigate the diagnostic value of CSF NF analysis to discriminate in relatively young dementia patients between frontotemporal lobe

  8. CSF neurofilament proteins in the differential diagnosis of dementia.

    NARCIS (Netherlands)

    Jong, D. de; Jansen, R.W.M.M.; Pijnenburg, Y.A.; Geel, W.J.A. van; Borm, G.F.; Kremer, H.P.H.; Verbeek, M.M.

    2007-01-01

    BACKGROUND: Neurofilament (NF) proteins are major cytoskeletal constituents of neurons. Increased CSF NF levels may reflect neuronal degeneration. OBJECTIVE: To investigate the diagnostic value of CSF NF analysis to discriminate in relatively young dementia patients between frontotemporal lobe

  9. The 5-HTTLPR variant in the serotonin transporter gene modifies degeneration of brain regions important for emotion in behavioral variant frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Jennifer S. Yokoyama

    2015-01-01

    Full Text Available The serotonin transporter length polymorphism (5-HTTLPR short allele (5-HTTLPR-s has been associated with differential susceptibility for anxiety and depression in multiple psychiatric disorders. 5-HTTLPR-s modifies the serotonergic systems that support emotion and behavioral regulation by reducing gene expression, which slows the reuptake of serotonin, and is associated with distinct morphological and functional effects. Serotonergic systems are also shown to be dysfunctional in behavioral variant frontotemporal dementia (bvFTD, a disease characterized by marked socioemotional dysfunction. However, studies of 5-HTTLPR-s effects in bvFTD have been inconsistent. Our objective was to investigate the patterns of gray matter volume by 5-HTTLPR-s genotype in both healthy older controls and bvFTD patients. We performed voxel-based morphometry of 179 cognitively normal older adults and 24 bvFTD cases to determine brain changes associated with dose (0/1/2 of 5-HTTLPR-s allele. 5-HTTLPR-s frequency did not differ between controls and bvFTD. We found a significant interaction effect whereby carrying more 5-HTTLPR-s alleles in bvFTD was associated with smaller volume in left inferior frontal gyrus (T = 4.86, PFWE = 0.03 and larger volume in right temporal lobe (T = 5.01, PFWE = 0.01. These results suggest that the 5-HTTLPR-s allele differentially influences brain morphology in bvFTD. We propose that patients with bvFTD and 5-HTTLPR-s have altered volumes in regions that support socioemotional behavior, which may be a developmental or disease-related compensation for altered serotonergic activity.

  10. Social influence on associative learning: double dissociation in high-functioning autism, early-stage behavioural variant frontotemporal dementia and Alzheimer's disease.

    Science.gov (United States)

    Kéri, Szabolcs

    2014-05-01

    Most of our learning activity takes place in a social context. I examined how social interactions influence associative learning in neurodegenerative diseases and atypical neurodevelopmental conditions primarily characterised by social cognitive and memory dysfunctions. Participants were individuals with high-functioning autism (HFA, n = 18), early-stage behavioural variant frontotemporal dementia (bvFTD, n = 16) and Alzheimer's disease (AD, n = 20). The leading symptoms in HFA and bvFTD were social and behavioural dysfunctions, whereas AD was characterised by memory deficits. Participants received three versions of a paired associates learning task. In the game with boxes test, objects were hidden in six candy boxes placed in different locations on the computer screen. In the game with faces, each box was labelled by a photo of a person. In the real-life version of the game, participants played with real persons. Individuals with HFA and bvFTD performed well in the computer games, but failed on the task including real persons. In contrast, in patients with early-stage AD, social interactions boosted paired associates learning up to the level of healthy control volunteers. Worse performance in the real life game was associated with less successful recognition of complex emotions and mental states in the Reading the Mind in the Eyes Test. Spatial span did not affect the results. When social cognition is impaired, but memory systems are less compromised (HFA and bvFTD), real-life interactions disrupt associative learning; when disease process impairs memory systems but social cognition is relatively intact (early-stage AD), social interactions have a beneficial effect on learning and memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Patient and caregiver goals for dementia care.

    Science.gov (United States)

    Jennings, Lee A; Palimaru, Alina; Corona, Maria G; Cagigas, Xavier E; Ramirez, Karina D; Zhao, Tracy; Hays, Ron D; Wenger, Neil S; Reuben, David B

    2017-03-01

    Most health outcome measures for chronic diseases do not incorporate specific health goals of patients and caregivers. To elicit patient-centered goals for dementia care, we conducted a qualitative study using focus groups of people with early-stage dementia and dementia caregivers. We conducted 5 focus groups with 43 participants (7 with early-stage dementia and 36 caregivers); 15 participants were Spanish-speaking. Verbatim transcriptions were independently analyzed line-by-line by two coders using both deductive and inductive approaches. Coded texts were grouped into domains and developed into a goal inventory for dementia care. Participants identified 41 goals for dementia care within five domains (medical care, physical quality of life, social and emotional quality of life, access to services and supports, and caregiver support). Caregiver goals included ensuring the safety of the person with dementia and managing caregiving stress. Participants with early-stage dementia identified engaging in meaningful activity (e.g., work, family functions) and not being a burden on family near the end of life as important goals. Participants articulated the need to readdress goals as the disease progressed and reported challenges in goal-setting when goals differed between the person with dementia and the caregiver (e.g., patient safety vs. living independently at home). While goals were similar among English- and Spanish-speaking participants, Spanish-speaking participants emphasized the need to improve community education about dementia. Patient- and caregiver-identified goals for care are different than commonly measured health outcomes for dementia. Future work should incorporate patient-centered goals into clinical settings and assess their usefulness for dementia care.

  12. Induced pluripotent stem cells (iPSCs) derived from af pre-symptomatic carrier of a R406W mutation in microtubule-associated protein tau (MAPT) causing frontotemporal dementia

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena Elisabeth; Hasholt, Lis Frydenreich

    2016-01-01

    Skin fibroblasts were obtained from a 28-year-old pre-symptomatic woman carrying a R406W mutation in microtubule-associated protein tau (MAPT), known to cause frontotemporal dementia. Induced pluripotent stem cell (iPSCs) were established by electroporation with episomal plasmids containing hOCT4...

  13. The Ekman 60 Faces Test as a diagnostic instrument in frontotemporal dementia

    National Research Council Canada - National Science Library

    Diehl-Schmid, Janine; Pohl, Corina; Ruprecht, Carolin; Wagenpfeil, Stefan; Foerstl, Hans; Kurz, Alexander

    2007-01-01

    .... The aim of the present study was to investigate if the Ekman 60 Faces Test, an instrument to test the recognition of basic facial emotions, enables the differentiation between patients with mild FTD...

  14. Imaging dementias

    Energy Technology Data Exchange (ETDEWEB)

    Savoiardo, M.; Grisoli, M. [Dept. of Neuroradiology, Istituto Nazionale Neurologico, Milan (Italy)

    2001-03-01

    Dementia is the progressive loss of intellectual functions due to involvement of cortical or subcortical areas. Specific involvement of certain brain areas in the different diseases leads to impairment of different functions, e. g., memory, language, visuospatial abilities, and behavior. Magnetic resonance imaging and other neuroradiological studies may indicate which structures are mainly or selectively involved in a demented patient, thus allowing clinical-radiological correlations. Clinical presentation and evolution of the disease, supported by imaging studies, may lead to a highly probable diagnosis. The most common disorders, or the most relevant from the neuroradiological point of view, such as Alzheimer's disease, frontotemporal dementia, vascular dementias, dementia associated with parkinsonism, Huntington's disease, Creutzfeldt-Jakob disease, and normal-pressure hydrocephalus, are briefly discussed. (orig.)

  15. Endogenous progesterone levels and frontotemporal dementia: modulation of TDP-43 and Tau levels in vitro and treatment of the A315T TARDBP mouse model

    Directory of Open Access Journals (Sweden)

    Theresa N. T. Dang

    2013-09-01

    Frontotemporal dementia (FTD is associated with motor neurone disease (FTD-MND, corticobasal syndrome (CBS and progressive supranuclear palsy syndrome (PSPS. Together, this group of disorders constitutes a major cause of young-onset dementia. One of the three clinical variants of FTD is progressive nonfluent aphasia (PNFA, which is focused on in this study. The steroid hormone progesterone (PROG is known to have an important role as a neurosteroid with potent neuroprotective and promyelination properties. In a case-control study of serum samples (39 FTD, 91 controls, low serum PROG was associated with FTD overall. In subgroup analysis, low PROG levels were significantly associated with FTD-MND and CBS, but not with PSPS or PNFA. PROG levels of >195 pg/ml were significantly correlated with lower disease severity (frontotemporal dementia rating scale for individuals with CBS. In the human neuroblastoma SK-N-MC cell line, exogenous PROG (9300–93,000 pg/ml had a significant effect on overall Tau and nuclear TDP-43 levels, reducing total Tau levels by ∼1.5-fold and increasing nuclear TDP-43 by 1.7- to 2.0-fold. Finally, elevation of plasma PROG to a mean concentration of 5870 pg/ml in an Ala315Thr (A315T TARDBP transgenic mouse model significantly reduced the rate of loss of locomotor control in PROG-treated, compared with placebo, mice. The PROG treatment did not significantly increase survival of the mice, which might be due to the limitation of the transgenic mouse to accurately model TDP-43-mediated neurodegeneration. Together, our clinical, cellular and animal data provide strong evidence that PROG could be a valid therapy for specific related disorders of FTD.

  16. Music Therapy System for Patients with Dementia

    OpenAIRE

    大島, 千佳; 中山, 功一; 安田, 清; 伊藤, 直樹; 西本, 一志; 細井, 尚人; 奥村, 浩

    2011-01-01

    We introduced three types of music therapy system. They were made for purpose of helping caregivers and/or patients with dementia enjoying a music performance. We discussed the efficacy of these systems for the caregivers and the patients.

  17. Agraphia in Mobile Text Messages in a Case of Amyotrophic Lateral Sclerosis with Frontotemporal Dementia.

    Science.gov (United States)

    Maeda, Kengo; Shiraishi, Tomoyuki; Idehara, Ryo

    2015-01-01

    We herein describe the case of a woman with amyotrophic lateral sclerosis (ALS) showing errors in her choice of Japanese kana characters in her mobile text messages and agraphia of the kana in her handwriting in spite of the absence of weakness, ataxia, or apraxia of her hands. Magnetic resonance imaging showed the atrophy of the frontal lobes. Single-photon emission computed tomography revealed hypoperfusion of the frontal lobes including Exner's area. Although patients with bulbar-onset ALS have been reported to show agraphia of handwriting, in this case the basis of her agraphia might have been the disturbance of the pathway converting phones to graphemes in series, by which errors of spelling or writing would appear in any modality of output.

  18. White matter tract signatures of impaired social cognition in frontotemporal lobar degeneration

    OpenAIRE

    Downey, Laura E.; Mahoney, Colin J.; Buckley, Aisling H.; Golden, Hannah L.; Henley, Susie M.; Nicole Schmitz; Schott, Jonathan M.; Simpson, Ivor J.; Sebastien Ourselin; Fox, Nick C.; Sebastian J. Crutch; Warren, Jason D.

    2015-01-01

    Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progre...

  19. Frontotemporal Dementias: Diagnosis

    Science.gov (United States)

    ... Studies Observational Studies Sharing our Stories Stories and Poems Blogs Art and Multimedia Published Tributes Resources Comstock ... diagnosis of FTD. This often results in a long and frustrating process of testing for other disorders ...

  20. Frontotemporal Dementia: Genetics

    Science.gov (United States)

    ... Calendar of Events Fundraising Events Conferences Press Releases Genetics of FTD After receiving a diagnosis of FTD ... that recent advances in science have brought the genetics of FTD into much better focus. In 2012, ...

  1. Frontotemporal Dementia (Pick's Disease)

    Science.gov (United States)

    ... been shown to slow the progression of FTD. Behavior modification may help control unacceptable or dangerous behaviors. Aggressive, ... been shown to slow the progression of FTD. Behavior modification may help control unacceptable or dangerous behaviors. Aggressive, ...

  2. Targeting TDP-43 phosphorylation by Casein Kinase-1δ inhibitors: a novel strategy for the treatment of frontotemporal dementia.

    Science.gov (United States)

    Alquezar, Carolina; Salado, Irene G; de la Encarnación, Ana; Pérez, Daniel I; Moreno, Fermín; Gil, Carmen; de Munain, Adolfo López; Martínez, Ana; Martín-Requero, Ángeles

    2016-04-30

    Mutations in the progranulin gene (GRN) are the most common cause of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). TDP-43 pathology is characterized by the hyperphosphorylation of the protein at Serine 409/410 residues. Casein kinase-1δ (CK-1δ) was reported to phosphorylate TDP-43 directly. Previous works from our laboratory described the presence of CDK6/pRb-dependent cell cycle alterations, and cytosolic accumulation of TDP-43 protein in lymphoblast from FTLD-TDP patients carriers of a loss-of function mutation in GRN gene (c.709-1G > A). In this work, we have investigated the effects of two brain penetrant CK-1δ inhibitors (IGS-2.7 and IGS-3.27) designed and synthetized in our laboratory on cell proliferation, TDP-43 phosphorylation and subcellular localization, as well as their effects on the known nuclear TDP-43 function repressing the expression of CDK6. We report here that both CK-1δ inhibitors (IGS-2.7 and IGS-3.27) normalized the proliferative activity of PGRN-deficient lymphoblasts by preventing the phosphorylation of TDP-43 fragments, its nucleo-cytosol translocation and the overactivation of the CDK6/pRb cascade. Moreover, ours results show neuroprotective effects of CK-1δ inhibitors in a neuronal cell model of induced TDP-43 phosphorylation. Our results suggest that modulating CK-1δ activity could be considered a novel therapeutic approach for the treatment of FTLD-TDP and other TDP-43 proteinopathies.

  3. Caregiver Stress and the Patient With Dementia.

    Science.gov (United States)

    Sanders, Amy E

    2016-04-01

    Informal caregivers (often, but not exclusively, family members) are essential to the clinical care of a patient with dementia. Most caregivers are untrained and unpaid. As a result, caregivers often experience stress caused by the caregiving experience; they are the "invisible second patients" in dementia care. Clinicians can help caregivers by supporting them in their role and by referring them to additional resources for support.

  4. Tetrabenazine treatment for stereotypies and tics associated with dementia.

    Science.gov (United States)

    Ondo, William G

    2012-01-01

    Stereotypies are frequently reported in frontotemporal dementia. Their pathophysiology and optimal treatment are largely unexplored. The author reports seven cases of marked stereotype in patients with probable frontotemporal dementia who were treated with tetrabenazine, a monoamine inhibitor. All patients had near-complete resolution of stereotypy. Six patients stopped tetrabenazine at some point, with return of their stereotype within 24 hours, which again improved in the four who restarted therapy. Efficacy has not waned over time. Tetrabenazine dramatically improved stereotypies in patients with dementia. This observation could increase understanding of this interesting phenotype.

  5. Tc-99m ECD brain SPET in the evaluation of dementia for institutionalized elderly patients

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Hoon; Park, Chan H.; Yoon, Seok Na.; Hwang, Kyung Hoon [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    2001-07-01

    Dementia is one of the clinically recognized indications of regional cerebral blood flow (rCBF) measurement by Tc-99m ECD brain SPET (Single Photon Emission Tomography). There is only limited number of institutions for elderly demented patients who are institutionalized in Korea and SPET is nor available at these institutions. The aim of the study is to evaluate rCBF SPET findings of the patients from such an institution. Thirty-one patients were reffered for rCBF SPET from Yongin Hyoja Hospital, Yongin. They were screened using NINCDS-ADRDA criteria for probable Alzheimers disease (AD) and dementia severity was assumed by the Mini-Mental State examination. In a quite, dim light room, patients were injected with 740 mBq (20mCi) Tc-99m ethyl cysteinate dimmer (ECD), Neurolite R, Dupont Pharmaceuticals, Billerica, MA, USA). SPET was acquired using fanbeam collimators and triple-head gamma camera (MultiSPECT III, Siemens medical systems. Inc. Hoffman Estates, III.USA). SPET was done one hour after the tracer injection and most of the patients needed sedation 30 minutes before the scan. SPET was evaluated visually by 2 nuclear medicine physicians blinded to clinical information. The SPET scans of 31 patients revealed 3 typical AD, 9 atypical AD patterns. Other dementia patterns were 4 cases of frontotemporal lobe dementia, 5 cases of frontal lobe dementia and 2 multifocal infarctions. Only cerebral atrophy is depicted in 8 patients and normal SPECT findings was noted in one patient. Patients who are institutionalized for dementia have varying SPET patterns as expected and SPET findings are useful in the management of these patients with more clearer clinical insight.

  6. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia

    Science.gov (United States)

    Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D'Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C.; Maletta, Raffaele G.; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, Massimo; Puca, Annibale A.; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew; Cusi, Daniele; Hardy, John; Momeni, Parastoo

    2015-01-01

    Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10−7 and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of –cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD–genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis. PMID:26154020

  7. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia.

    Science.gov (United States)

    Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D'Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C; Maletta, Raffaele G; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, Massimo; Puca, Annibale A; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew; Cusi, Daniele; Hardy, John; Momeni, Parastoo

    2015-10-01

    Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10(-7) and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis.

  8. Reduced miR-659-3p levels correlate with progranulin increase in hypoxic conditions: implications for frontotemporal dementia.

    Directory of Open Access Journals (Sweden)

    Paola ePiscopo

    2016-05-01

    Full Text Available Progranulin (PGRN is a secreted protein expressed ubiquitously throughout the body, including the brain, where it localizes in neurons and activated microglia. Loss-of-function mutations in the GRN gene are an important cause of familial Frontotemporal Lobar Degeneration (FTLD. PGRN has a neurotrophic and anti-inflammatory activity, and it is neuroprotective in several injury conditions, such as oxygen or glucose deprivation, oxidative injury, and hypoxic stress. Indeed, we have previously demonstrated that hypoxia induces the up-regulation of GRN transcripts. Several studies have shown microRNAs involvement in hypoxia. Moreover, in FTLD patients with a genetic variant of GRN (rs5848, the reinforcement of miR-659-3p binding site has been suggested to be a risk factor. Here, we report that miR-659-3p interacts directly with GRN 3’UTR as shown by luciferase assay in HeLa cells and ELISA and Western Blot analysis in HeLa and Kelly cells. Moreover, we demonstrate the physical binding between GRN mRNA and miR-659-3p employing a miRNA capture-affinity technology in SK-N-BE and Kelly cells. In order to study miRNAs involvement in hypoxia-mediated up-regulation of GRN, we evaluated miR-659-3p levels in SK-N-BE cells after 24h of hypoxic treatment, finding them inversely correlated to GRN transcripts. Furthermore, we analyzed an animal model of asphyxia, finding that GRN mRNA levels increased at post-natal day (pnd 1 and pnd 4 in rat cortices subjected to asphyxia in comparison to control rats and miR-659-3p decreased at pnd 4 just when GRN reached the highest levels. Our results demonstrate the interaction between miR-659-3p and GRN transcript and the involvement of miR-659-3p in GRN up-regulation mediated by hypoxic/ischemic insults.

  9. Creativity and dementia: a review.

    Science.gov (United States)

    Palmiero, Massimiliano; Di Giacomo, Dina; Passafiume, Domenico

    2012-08-01

    In these last years, creativity was found to play an important role for dementia patients in terms of diagnosis and rehabilitation strategies. This led us to explore the relationships between dementia and creativity. At the aim, artistic creativity and divergent thinking are considered both in non-artists and artists affected by different types of dementia. In general, artistic creativity can be expressed in exceptional cases both in Alzheimer's disease and Frontotemporal dementia, whereas divergent thinking decreases in dementia. The creation of paintings or music is anyway important for expressing emotions and well-being. Yet, creativity seems to emerge when the right prefrontal cortex, posterior temporal, and parietal areas are relatively intact, whereas it declines when these areas are damaged. However, enhanced creativity in dementia is not confirmed by controlled studies conducted in non-artists, and whether artists with dementia can show creativity has to be fully addressed. Future research directions are suggested.

  10. Capillary electrophoresis-mass spectrometry-based metabolome analysis of serum and saliva from neurodegenerative dementia patients.

    Science.gov (United States)

    Tsuruoka, Mayuko; Hara, Junko; Hirayama, Akiyoshi; Sugimoto, Masahiro; Soga, Tomoyoshi; Shankle, William R; Tomita, Masaru

    2013-10-01

    Despite increasing global prevalence, the precise pathogenesis and terms for objective diagnosis of neurodegenerative dementias remain controversial, and comprehensive understanding of the disease remains lacking. Here, we conducted metabolomic analysis of serum and saliva obtained from patients with neurodegenerative dementias (n = 10), including Alzheimer's disease, frontotemporal lobe dementia, and Lewy body disease, as well as from age-matched healthy controls (n = 9). Using CE-TOF-MS, six metabolites in serum (β-alanine, creatinine, hydroxyproline, glutamine, iso-citrate, and cytidine) and two in saliva (arginine and tyrosine) were significantly different between dementias and controls. Using multivariate analysis, serum was confirmed as a more efficient biological fluid for diagnosis compared to saliva; additionally, 45 metabolites in total were identified as candidate markers that could discriminate at least one pair of diagnostic groups from the healthy control group. These metabolites possibly provide an objective method for diagnosing dementia-type by multiphase screening. Moreover, diagnostic-type-dependent differences were observed in several tricarboxylic acid cycle compounds detected in serum, indicating that some pathways in glucose metabolism may be altered in dementia patients. This pilot study revealed novel alterations in metabolomic profiles between various neurodegenerative dementias, which would contribute to etiological investigations.

  11. Anesthesia for the patient with dementia

    DEFF Research Database (Denmark)

    Funder, Kamilia S; Steinmetz, Jacob; Rasmussen, Lars S

    2010-01-01

    With a growing aging population, more patients suffering from dementia are expected to undergo surgery, thus being exposed to either general or regional anesthesia. This calls for specific attention ranging from the legal aspects of obtaining informed consent in demented patients to deciding...

  12. Anesthesia for the patient with dementia

    DEFF Research Database (Denmark)

    Funder, Kamilia S; Steinmetz, Jacob; Rasmussen, Lars S

    2010-01-01

    With a growing aging population, more patients suffering from dementia are expected to undergo surgery, thus being exposed to either general or regional anesthesia. This calls for specific attention ranging from the legal aspects of obtaining informed consent in demented patients to deciding...

  13. Music Therapy with Ethnic Music for Dementia Patients

    Directory of Open Access Journals (Sweden)

    Yuki Tanaka

    2012-12-01

    Conclusion: Our results revealed characteristic responses of dementia patients onto the Japanese music, and we expect our result provides an evidence for better music therapy for dementia patients with Japanese culture.

  14. Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration.

    Science.gov (United States)

    Davidson, Yvonne S; Robinson, Andrew C; Flood, Louis; Rollinson, Sara; Benson, Bridget C; Asi, Yasmine T; Richardson, Anna; Jones, Matthew; Snowden, Julie S; Pickering-Brown, Stuart; Lashley, Tammaryn; Mann, David M A

    2017-06-30

    Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter personality and cognition. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP E2 was performed on sections of frontal and temporal cortex with hippocampus from 80 patients with FTLD, stratified by pathology into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those with no known mutation, and on 10 healthy controls. Semi-quantitative analysis assessed hnRNP staining in frontal and temporal cortex, and in dentate gyrus (DG) of hippocampus, in the different pathology and genetic groups. We find that hnRNP E2 immunostaining detects the TDP-43 positive dystrophic neurites (DN) within frontal and temporal cortex, and the neuronal cytoplasmic inclusions (NCI) seen in DG granule cells, characteristic of patients with Semantic Dementia (SD) and type C TDP-43 pathology, but did not detect TDP-43 or tau inclusions in any of the other pathological or genetic variants of FTLD. Double immunofluorescence for hnRNP E2 and TDP-43 showed most TDP-43 immunopositive DN to contain hnRNP E2. Present findings indicate an association between TDP-43 and hnRNP E2 which might underlie the pathogenetic mechanism of this form of FTLD.

  15. COMPARATIVE EFFECTIVENESS OF MCI and DEMENTIA TREATMENTS IN A COMMUNITY-BASED DEMENTIA PRACTICE

    Science.gov (United States)

    2016-08-04

    Mild Cognitive Impairment; Dementia; Hypoxia; Hyperhomocysteinemia; Vitamin B 12 Deficiency; Iron Deficiency; Anemia; TBI; Neurodegenerative Disorders; Alzheimer's Disease; Vascular Dementia; Brain Injuries; Tauopathies; Parkinson's Disease; Lewy Body Dementia; Frontotemporal Dementia; TDP-43 Proteinopathies

  16. Mild behavioral impairment and risk of dementia

    Science.gov (United States)

    Taragano, FE; Allegri, RF; Krupitzki, H; Sarasola, D; Serrano, CM; Loñ, L; Lyketsos, CG

    2009-01-01

    Background Mild cognitive impairment (MCI) is a transitional state between normal ageing and dementia, at least for some patients. Behavioral symptoms in MCI are associated with a higher risk of dementia, but their association with dementia risk in patients without MCI is unknown. Mild Behavioral Impairment (MBI) refers to a late life syndrome with prominent psychiatric and related behavioral symptoms in the absence of prominent cognitive symptoms, which may also be a dementia prodrome. Objective To compare MCI and MBI patients and to estimate the risk of dementia development in these two groups. Method A consecutive series of 358 patients (239 with MCI; and 119 with MBI) presenting to an outpatient general hospital specialty clinic were followed for up to 5 years until conversion to dementia or censoring. Results 34% of MCI patients and over 70% of patients with MBI developed dementia (Logrank p=0.011). MBI patients without cognitive symptoms were more likely to develop dementia (Logrank p<0.001). MBI patients were more likely to develop dementia due to frontotemporal degeneration (FTD) as opposed to Alzheimer’s dementia (AD). Conclusion MBI appears to be a transitional state between normal ageing and dementia. MBI (specifically those without cognitive symptoms) may confer a higher risk for dementia than MCI and is likely an FTD prodrome in many cases. These findings have implications for the early detection, prevention, and treatment of patients with dementia in late life, by focusing on the emergence of new behavioral symptoms. PMID:19323967

  17. Recent advance of MAPT gene in frontotemporal dementia%额颞叶痴呆MAPT基因的研究进展

    Institute of Scientific and Technical Information of China (English)

    李明月; 王群

    2015-01-01

    额颞叶痴呆是一种隐匿起病、进行性的神经变性性疾病,是仅次于阿尔茨海默病的第二大常见早发型痴呆类型,具有高度遗传异质性。近年来,额颞叶痴呆的基因研究正在如火如荼进行,目前已证实7种单基因突变可导致额颞叶痴呆。其中MAPT基因是最早被发现与额颞叶痴呆有关的致病基因,也是最主要最常见的一种致病基因。本文将就MAPT基因的结构、功能及其突变类型、动物模型、未来治疗方向在额颞叶痴呆中的研究现状进行综述。%Frontotemporal dementia (FTD) is an insidious onset, progressive neurodegenerative disease and is the second most common young-onset dementia after Alzheimer’s disease (AD), with genetic heterogeneity. In recent years, genetic research in FTD is gaining momentum. Seven single causative genes have been discovered, whose mutations could lead to FTD. Among these, microtubule associated protein tau (MAPT) was the first gene to be discovered, which is the most important and the most common causative gene. This article introduced the structure, function, mutation types, animal models and potential therapeutic strategies of MAPT on FTD.

  18. miRNA expression profiles in cerebrospinal fluid and blood of patients with Alzheimer’s disease and other types of dementia: an exploratory study

    DEFF Research Database (Denmark)

    Sølvsten Sørensen, Sofie; Nygaard Hillig, Ann-Britt; Christensen, Thomas

    2016-01-01

    BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules that function as posttranscriptional regulators of gene expression. Measurements of miRNAs in cerebrospinal fluid (CSF) and blood have just started gaining attention as a novel diagnostic tool for various neurological conditions....... The purpose of this exploratory investigation was to analyze the expression of miRNAs in CSF and blood of patients with Alzheimer's disease (AD) and other neurodegenerative disorders in order to identify potential miRNA biomarker candidates able to separate AD from other types of dementia. METHODS: CSF...... was collected by lumbar puncture performed on 10 patients diagnosed with AD and 10 patients diagnosed with either vascular dementia, frontotemporal dementia or dementia with Lewy bodies. Blood samples were taken immediately after. Total RNA was extracted from cell free fractions of CSF and plasma...

  19. Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability

    Directory of Open Access Journals (Sweden)

    M. Catarina Silva

    2016-09-01

    Full Text Available Frontotemporal dementia (FTD and other tauopathies characterized by focal brain neurodegeneration and pathological accumulation of proteins are commonly associated with tau mutations. However, the mechanism of neuronal loss is not fully understood. To identify molecular events associated with tauopathy, we studied induced pluripotent stem cell (iPSC-derived neurons from individuals carrying the tau-A152T variant. We highlight the potential of in-depth phenotyping of human neuronal cell models for pre-clinical studies and identification of modulators of endogenous tau toxicity. Through a panel of biochemical and cellular assays, A152T neurons showed accumulation, redistribution, and decreased solubility of tau. Upregulation of tau was coupled to enhanced stress-inducible markers and cell vulnerability to proteotoxic, excitotoxic, and mitochondrial stressors, which was rescued upon CRISPR/Cas9-mediated targeting of tau or by pharmacological activation of autophagy. Our findings unmask tau-mediated perturbations of specific pathways associated with neuronal vulnerability, revealing potential early disease biomarkers and therapeutic targets for FTD and other tauopathies.

  20. Frontotemporal dementia linked to chromosome 3 (FTD-3)--current concepts and the detection of a previously unknown branch of the Danish FTD-3 family

    DEFF Research Database (Denmark)

    Lindquist, S.G.; Braedgaard, H.; Svenstrup, K.

    2008-01-01

    entities of FTD have involved identification of several new causative genes. METHODS AND RESULTS: We report the finding of a truncating mutation in the CHMP2B gene (c.532-1G>C) in a patient with early onset dementia. The patient was previously not known to be related to the single Danish pedigree known...

  1. Transcranial magnetic stimulation in patients with early cortical dementia: A pilot study

    Directory of Open Access Journals (Sweden)

    Thomas Gregor Issac

    2013-01-01

    Full Text Available Context: The diagnostic accuracy of the currently available tools carries poor sensitivity resulting in significant delay in specific diagnosis of cortical dementias. Considering the properties of default mode networking of the brain it is highly probable that specific changes may be seen in frontotemporal dementias (FTDs and Alzheimer′s disease sufficiently early. Aim: The aim of this study is to look for changes in Transcranial Magnetic Stimulation (TMS in cortical dementia. Materials and Methods: Evaluated with a single pulse TMS with the figure of eight coil and recorded from right first dorsal interossei (FDI. Resting Motor Threshold (RMT was estimated on the opposite motor cortex (T1. Second site of stimulation was cervical spine at C7-T2. Central motor conduction time (CMCT is equal toT1-T2.Silent Period (SP identified by applying TMS pulse to contracting FDI. Conclusions: RMT was reduced in seven out of eight Alzheimer′s dementias. CMCT was in the upper limit of normal in both patients with FTD. The most consistent observation was that SP was reduced and there were escape discharges noticed during the SP suggesting increased cortical excitability and decreased cortical inhibition. This suggests probable early asymptomatic changes in the gamma-aminobutyric acid (GABA nergic and cholinergic system is taking place. This if confirmed may give some insight into early diagnosis and therapeutic role of GABA agonists in these disorders.

  2. Transcranial magnetic stimulation in patients with early cortical dementia: A pilot study.

    Science.gov (United States)

    Issac, Thomas Gregor; Chandra, S R; Nagaraju, B C

    2013-10-01

    The diagnostic accuracy of the currently available tools carries poor sensitivity resulting in significant delay in specific diagnosis of cortical dementias. Considering the properties of default mode networking of the brain it is highly probable that specific changes may be seen in frontotemporal dementias (FTDs) and Alzheimer's disease sufficiently early. The aim of this study is to look for changes in Transcranial Magnetic Stimulation (TMS) in cortical dementia. Evaluated with a single pulse TMS with the figure of eight coil and recorded from right first dorsal interossei (FDI). Resting Motor Threshold (RMT) was estimated on the opposite motor cortex (T1). Second site of stimulation was cervical spine at C7-T2. Central motor conduction time (CMCT) is equal toT1-T2. Silent Period (SP) identified by applying TMS pulse to contracting FDI. RMT was reduced in seven out of eight Alzheimer's dementias. CMCT was in the upper limit of normal in both patients with FTD. The most consistent observation was that SP was reduced and there were escape discharges noticed during the SP suggesting increased cortical excitability and decreased cortical inhibition. This suggests probable early asymptomatic changes in the gamma-aminobutyric acid (GABA) nergic and cholinergic system is taking place. This if confirmed may give some insight into early diagnosis and therapeutic role of GABA agonists in these disorders.

  3. Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

    Science.gov (United States)

    2017-08-23

    FTLD; Progressive Supranuclear Palsy (PSP); Frontotemporal Dementia (FTD); Corticobasal Degeneration (CBD); PPA Syndrome; Behavioral Variant Frontotemporal Dementia (bvFTD); Semantic Variant Primary Progressive Aphasia (svPPA); Nonfluent Variant Primary Progressive Aphasia (nfvPPA); FTD With Amyotrophic Lateral Sclerosis (FTD/ALS); Amyotrophic Lateral Sclerosis (ALS); Oligosymptomatic PSP (oPSP); Corticobasal Syndrome (CBS)

  4. Recognition of Facial Expressions of Different Emotional Intensities in Patients with Frontotemporal Lobar Degeneration

    Directory of Open Access Journals (Sweden)

    Roy P. C. Kessels

    2007-01-01

    Full Text Available Behavioural problems are a key feature of frontotemporal lobar degeneration (FTLD. Also, FTLD patients show impairments in emotion processing. Specifically, the perception of negative emotional facial expressions is affected. Generally, however, negative emotional expressions are regarded as more difficult to recognize than positive ones, which thus may have been a confounding factor in previous studies. Also, ceiling effects are often present on emotion recognition tasks using full-blown emotional facial expressions. In the present study with FTLD patients, we examined the perception of sadness, anger, fear, happiness, surprise and disgust at different emotional intensities on morphed facial expressions to take task difficulty into account. Results showed that our FTLD patients were specifically impaired at the recognition of the emotion anger. Also, the patients performed worse than the controls on recognition of surprise, but performed at control levels on disgust, happiness, sadness and fear. These findings corroborate and extend previous results showing deficits in emotion perception in FTLD.

  5. Sexual disinhibition and dementia.

    Science.gov (United States)

    Cipriani, Gabriele; Ulivi, Martina; Danti, Sabrina; Lucetti, Claudio; Nuti, Angelo

    2016-03-01

    To describe inappropriate sexual behaviour (ISB) observed in patients with dementia, we conducted searches using the Cochrane Library, PubMed, and Web of Science to find relevant articles, chapters, and books published from 1950 to 2014. Search terms used included 'hypersexuality', 'inappropriate sexual behaviors', and 'dementia'. Publications found through this indexed search were reviewed for further relevant references. Sexuality is a human's need to express intimacy, but persons with dementia may not know how to appropriately meet their needs for closeness and intimacy due to their decline in cognition. Generally, the interaction among brain, physical, psychological, and environmental factors can create what we call ISB. The most likely change in the sexual behaviour of a person with dementia is indifference. However, ISB in dementia appear to be of two types--intimacy-seeking and disinhibited--that differ in their association with dementia type, dementia severity and, possibly, other concurrent behavioural disorder. Tensions develop from uncertainties regarding which, or when, behaviours are to be considered 'inappropriate' (i.e. improper) or abnormal. While most ISB occur in the moderate to severe stages of Alzheimer's dementia, they may also be seen in early stages of frontotemporal dementia because of the lack of insight and disinhibition. ISB are often better managed by non-pharmacological means, as patients may be less responsive to psychoactive therapies, but non-pharmacological interventions do not always stop the behaviour. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  6. Neuropsychological patterns in magnetic resonance imaging-defined subgroups of patients with degenerative dementia

    Science.gov (United States)

    LISTERUD, JOHN; POWERS, CHIVON; MOORE, PEACHIE; LIBON, DAVID J.; GROSSMAN, MURRAY

    2010-01-01

    We hypothesized that specific neuropsychological deficits were associated with specific patterns of atrophy. A magnetic resonance imaging volumetric study and a neuropsychological protocol were obtained for patients with several frontotemporal lobar dementia phenotypes including a social/dysexecutive (SOC/EXEC, n = 17), progressive nonfluent aphasia (n = 9), semantic dementia (n = 7), corticobasal syndrome (n = 9), and Alzheimer’s disease (n = 21). Blinded to testing results, patients were partitioned according to pattern of predominant cortical atrophy; our partitioning algorithm had been derived using seriation, a hierarchical classification technique. Neuropsychological test scores were regressed versus these atrophy patterns as fixed effects using the covariate total atrophy as marker for disease severity. The results showed the model accounted for substantial variance. Furthermore, the “large-scale networks” associated with each neuropsychological test conformed well to the known literature. For example, bilateral prefrontal cortical atrophy was exclusively associated with SOC/EXEC dysfunction. The neuropsychological principle of “double dissociation” was supported not just by such active associations but also by the “silence” of locations not previously implicated by the literature. We conclude that classifying patients with degenerative dementia by specific pattern of cortical atrophy has the potential to predict individual patterns of cognitive deficits. PMID:19402932

  7. Functional Neuroimaging in Dementia

    NARCIS (Netherlands)

    J.M. Papma (Janne)

    2012-01-01

    textabstractDementia refers to a clinical syndrome of cognitive deterioration and difficulty in the performance of activities of daily living. The most common cause of dementia is Alzheimer’s disease (AD), followed by vascular dementia (VaD) at old age and frontotemporal dementia (FTD) at young onse

  8. Novel marker for the onset of frontotemporal dementia: early increase in activity-dependent neuroprotective protein (ADNP in the face of Tau mutation.

    Directory of Open Access Journals (Sweden)

    Yulie Schirer

    Full Text Available Tauopathy, a major pathology in Alzheimer's disease, is also found in ~50% of frontotemporal dementias (FTDs. Tau transcript, a product of a single gene, undergoes alternative splicing to yield 6 protein species, each with either 3 or 4 microtubule binding repeat domains (tau 3R or 4R, associated with dynamic and stable microtubules, respectively. While the healthy human brain shows a 1/1 ratio of tau 3R/4R, this ratio may be dramatically changed in the FTD brain. We have previously discovered that activity-dependent neuroprotective protein (ADNP is essential for brain formation in the mouse, with ADNP+/- mice exhibiting tauopathy, age-driven neurodegeneration and behavioral deficits. Here, in transgenic mice overexpressing a mutated tau 4R species, in the cerebral cortex but not in the cerebellum, we showed significantly increased ADNP expression (~3-fold transcripts in the cerebral cortex of young transgenic mice (~disease onset, but not in the cerebellum, as compared to control littermates. The transgene-age-related increased ADNP expression paralleled augmented dynamic tau 3R transcript level compared to control littermates. Blocking mutated tau 4R transgene expression resulted in normalization of ADNP and tau 3R expression. ADNP was previously shown to be a member of the SWItch/Sucrose NonFermentable (SWI/SNF chromatin remodeling complex. Here, Brahma (Brm, a component of the SWI/SNF complex regulating alternative splicing, showed a similar developmental expression pattern to ADNP. Immunoprecipitations further suggested Brm-ADNP interaction coupled to ADNP - polypyrimidine tract-binding protein (PTB-associated splicing factor (PSF-binding, with PSF being a direct regulator of tau transcript splicing. It should be noted that although we have shown a correlation between levels of ADNP and tau isoform expression three months of age, we are not presenting evidence of a direct link between the two. Future research into ADNP/tau relations is

  9. Induced pluripotent stem cells (iPSCs) derived from a symptomatic carrier of a S305I mutation in the microtubule-associated protein tau (MAPT)-gene causing frontotemporal dementia

    DEFF Research Database (Denmark)

    Nimsanor, Natakarn; Jørring, Ida; Rasmussen, Mikkel A.

    2016-01-01

    Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the gene coding the microtubule-associated protein tau (MAPT) can cause FTDP-17 but the underlying mechanisms of the disease are still unknown. Induce...... pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required neuronal cell type. Here, we report the generation of iPSCs from a 44-year-old symptomatic woman carrying a S305I mutation in the MAPT-gene....

  10. [Spontaneous speech prosody and discourse analysis in schizophrenia and Fronto Temporal Dementia (FTD) patients].

    Science.gov (United States)

    Martínez, Angela; Felizzola Donado, Carlos Alberto; Matallana Eslava, Diana Lucía

    2015-01-01

    Patients with schizophrenia and Frontotemporal Dementia (FTD) in their linguistic variants share some language characteristics such as the lexical access difficulties, disordered speech with disruptions, many pauses, interruptions and reformulations. For the schizophrenia patients it reflects a difficulty of affect expression, while for the FTD patients it reflects a linguistic issue. This study, through an analysis of a series of cases assessed Clinic both in memory and on the Mental Health Unit of HUSI-PUJ (Hospital Universitario San Ignacio), with additional language assessment (analysis speech and acoustic analysis), present distinctive features of the DFT in its linguistic variants and schizophrenia that will guide the specialist in finding early markers of a differential diagnosis. In patients with FTD language variants, in 100% of cases there is a difficulty understanding linguistic structure of complex type; and important speech fluency problems. In patients with schizophrenia, there are significant alterations in the expression of the suprasegmental elements of speech, as well as disruptions in discourse. We present how depth language assessment allows to reassess some of the rules for the speech and prosody analysis of patients with dementia and schizophrenia; we suggest how elements of speech are useful in guiding the diagnosis and correlate functional compromise in everyday psychiatrist's practice. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  11. EFFECT OF ACUPUNCTURE ON THE INTELLIGENCE OF CEREBROVASCULAR DEMENTIA PATIENT

    Institute of Scientific and Technical Information of China (English)

    陈邦国

    2000-01-01

    Cerebrovascular dementia is a common disese in the old and medium-aged people. Its morbidity constitutes about 10-20% of all the dementia patients and results mainly from all-round decline of the brain function due to cerebral atheroscleorsis and cerebral infarction. The author of the present paper adopted acupuncture therapy to; treat this kind of disease and observed its effect on dementia patient's intelligence. Here is the report.

  12. [Prevalence of dementia in institutionalized patients. The RESYDEM study].

    Science.gov (United States)

    López Mongil, Rosa; López Trigo, J Antonio; Castrodeza Sanz, F Javier; Tamames Gómez, Sonia; León Colombo, Teresa

    2009-01-01

    To determine the prevalence of dementia in nursing homes in Spain and to analyze the associated factors in an elderly population in the institutional setting. We performed a multicenter, cross-sectional, observational study of 852 residents of public, private and state-assisted nursing homes throughout Spain. Dementia was diagnosed according to the DSM-IV-TR clinical criteria. The Hughes Clinical Dementia Rating scale was used to measure global impairment or the global severity of dementia. Sociodemographic, clinical and neuropsychological variables, together with the pharmacological treatments prescribed to the participants, were recorded. The overall prevalence of dementia was 61.7% (95% CI 58.4-65.1) and that of Alzheimer's disease was 16.9% (95% CI 14.3-19.5). Vascular dementia was found in 7.3% (95% CI 5.5-9.1). Female sex was independently associated with a greater frequency of dementia. The prevalence of dementia increased with age. Only 18.8% (95% CI 15.4-22.3) of the patients diagnosed with dementia received specific treatment for the disorder. Two-thirds of the elderly persons living in nursing homes in Spain have dementia. Undertreatment of this disease is common. Increased awareness among health care professionals is important for the early diagnosis and appropriate management of dementia, which would represent a radical change in the approach to this disease.

  13. Advances in art therapy for patients with dementia

    Institute of Scientific and Technical Information of China (English)

    Qiu-Yue Wang; Dong-Mei Li

    2016-01-01

    In this article, the theoretical basis and development status of art therapy are introduced, and the intervention methods and effectiveness of art therapy in patients with dementia are reviewed. To date, nursing intervention via art therapy with dementia patients in China has been rarely investigated, and the design of this type of investigation must be improved.

  14. Language Assessment in Hindi-English Bilingual Patients with Dementia

    Science.gov (United States)

    Pauranik, Apoorva

    2010-01-01

    The paper provides detailed assessment of a multilingual dementia patients using Boston Diagnostic Aphasia Examination (BDAE) adapted into Hindi by the author. After providing a brief review of literature on Dementia as understood in the west, the responses of the patient under different components of the BDAE are presented. The latter part of…

  15. Diminished self-conscious emotional responding in frontotemporal lobar degeneration patients.

    Science.gov (United States)

    Sturm, Virginia E; Ascher, Elizabeth A; Miller, Bruce L; Levenson, Robert W

    2008-12-01

    Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that dramatically alters social and emotional behavior. Recent work has suggested that self-conscious emotions (e.g., embarrassment) may be particularly vulnerable to disruption in this disease. Self-conscious emotions require the ability to monitor the self in relation to others. These abilities are thought to be subserved by brain regions (e.g., medial prefrontal, anterior cingulate, and insula) that are particularly vulnerable to damage in FTLD. This study examined emotional responding (expressive behavior, peripheral physiology, and subjective experience) in 24 FTLD patients and 16 cognitively normal control participants using a karaoke task known to elicit self-conscious emotion reliably and a nonemotional control task (isometric handgrip). Results indicated that FTLD patients showed diminished self-conscious emotional behavior (embarrassment and amusement) and diminished physiological responding while watching themselves singing. No differences were found between patients and controls in the nonemotional control task. These findings offer evidence of marked disruption of self-conscious emotional responding in FTLD. Diminished self-conscious emotional responding likely contributes significantly to social inappropriateness and other behavioral abnormalities in FTLD.

  16. Faulty Suppression of Irrelevant Material in Patients with Thought Disorder Linked to Attenuated Frontotemporal Activation

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    S. M. Arcuri

    2012-01-01

    Full Text Available Formal thought disorder is a feature schizophrenia that manifests as disorganized, incoherent speech, and is associated with a poor clinical outcome. The neurocognitive basis of this symptom is unclear but it is thought to involve an impairment in semantic processing classically described as a loosening of meaningful associations. Using a paradigm derived from the n400 event-related, potential, we examined the extent to which regional activation during semantic processing is altered in schizophrenic patients with formal thought disorder. Ten healthy control and 18 schizophrenic participants (9 with and 9 without formal thought disorder performed a semantic decision sentence task during an event-related functional magnetic resonance imaging experiment. We employed analysis of variance to estimate the main effects of semantic congruency and groups on activation and specific effects of formal thought disorder were addressed using post-hoc comparisons. We found that the frontotemporal network, normally engaged by a semantic decision task, was underactivated in schizophrenia, particularly in patients with FTD. This network is implicated in the inhibition of automatically primed stimuli and impairment of its function interferes with language processing and contributes to the production of incoherent speech.

  17. Oral Findings and Health Status among Turkish Geriatric Patients with or without Dementia (Oral Lesions and Dementia Patients

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    Hakki Oguz Kazancioglu

    2013-06-01

    Conclusion: Oral mucosal lesions are more common in patients with dementia and dental care should be performed regularly for this group. In addition, because removable prostheses can be lost by patients with dementia, implant-supported fixed prostheses should be preferred for this group.

  18. SSUES OF THE CARE OF PATIENTS WITH SYNDROM OF DEMENTIA

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    Jedlinská Martina

    2013-12-01

    Full Text Available This article aims to acquaint the reader with the characteristics and problems of care for patients with dementia and options selected inpatient care for these patients in the Pardubice region. The theoretical part provides an overview of the issue of care for patients with dementia or dementia. The empirical part focuses on the description of selected characteristics of clients in the health-care facility, which is an example of good practice care for the elderly. In these age group is the greatest prevalence of dementia and syndrom of dementia as diagnosed disease. The discussion paper presents a reflection on the possible reasons for placing these clients in various types of inpatient facilities after discharge from aftercare and the circumstances of care for these clients.

  19. Time trends in antipsychotic drug use in patients with dementia

    DEFF Research Database (Denmark)

    Nørgaard, Ane; Jensen-Dahm, Christina; Gasse, Christiane;

    2016-01-01

    BACKGROUND: Antipsychotics are often used to treat neuropsychiatric symptoms in dementia, but the evidence for effect is limited. Antipsychotics have been associated with increased risk of adverse events and mortality in patients with dementia, leading to safety regulations worldwide. OBJECTIVE......: To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses......, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012...

  20. Ethnic Variations in Prognosis of Patients with Dementia

    DEFF Research Database (Denmark)

    Agyemang, Charles; van de Vorst, Irene E.; Koek, Huiberdina L.

    2017-01-01

    rate, ethnic minority patients with dementia did not have a worse prognosis. Given the poor prognosis of dementia, timely and targeted advance care planning is essential, particularly in ethnic minority groups who are mired by cultural barriers and where uptake of advance care planning is known...

  1. Dementias show differential physiological responses to salient sounds

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    Phillip David Fletcher

    2015-03-01

    Full Text Available Abnormal responsiveness to salient sensory signals is often a prominent feature of dementia diseases, particularly the frontotemporal lobar degenerations, but has been little studied. Here we assessed processing of one important class of salient signals, looming sounds, in canonical dementia syndromes. We manipulated tones using intensity cues to create percepts of salient approaching (‘looming’ or less salient withdrawing sounds. Pupil dilatation responses and behavioural rating responses to these stimuli were compared in patients fulfilling consensus criteria for dementia syndromes (semantic dementia, n=10; behavioural variant frontotemporal dementia, n=16, progressive non-fluent aphasia, n=12; amnestic Alzheimer’s disease, n=10 and a cohort of 26 healthy age-matched individuals. Approaching sounds were rated as more salient than withdrawing sounds by healthy older individuals but this behavioural response to salience did not differentiate healthy individuals from patients with dementia syndromes. Pupil responses to approaching sounds were greater than responses to withdrawing sounds in healthy older individuals and in patients with semantic dementia: this differential pupil response was reduced in patients with progressive nonfluent aphasia and Alzheimer’s disease relative both to the healthy control and semantic dementia groups, and did not correlate with nonverbal auditory semantic function. Autonomic responses to auditory salience are differentially affected by dementias and may constitute a novel biomarker of these diseases.

  2. Lexical-semantic knowledge about food in patients with different types of dementia

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    Raffaella Ida Rumiati

    2014-04-01

    Full Text Available While many theories agree that the conceptual knowledge is organized in categories, there is less agreement on the underlying organizational principle (e.g. Warrington & Shallice, 1984, Caramazza & Shelton, 1998; Capitani et al., 2003. Previous neuropsychological studies on semantic categories failed to clearly characterize the status of food as a category as they did not carefully distinguish between natural food and transformed food. Exploring how natural food and transformed food items are processed in patients suffering from primary dementia can allow us to test the theories of how semantic knowledge is organized in the brain. Thirty patients and 15 healthy controls matched for age and education took part in the study . Thirteen patients received a presumptive diagnosis of fronto-temporal dementia (FTD, 3 patients of Semantic Dementia (SD, and 14 of Alzheimer Dementia (AD. All participants performed 3 tasks tapping lexical-semantic knowledge about food and non-food items: confrontation naming (Task 1, categorization (Task 2, and word-to-picture matching (Task 3. Moreover, half food items were natural (e.g., apple and half transformed (e.g. grana cheese, while non-food items were half non edible natural items (e.g., plant and half kitchen implements. The results showed that, overall, patients performed poorer than controls on Tasks 1 and 3, with FTD-SD patients being more impaired than AD patients. When we compared performance on food versus non-food items, we observed that patients performed better on naming food than non-food items (Task 1. Specifically, FTD-SD patients displayed a significant difference between food and non-food items, while AD patients showed no difference. On Task 3 the same pattern was obtained. In addition, we observed that, across tasks, transformed food was processed better than natural food. These findings suggest that lexical-semantic processes are more prone to degradation in patients FTD-SD than in AD patients

  3. Prevalence of dementia in elderly patients with hip fracture.

    Science.gov (United States)

    Yiannopoulou, Konstantina G; Anastasiou, Ioannis P; Ganetsos, Theodore K; Efthimiopoulos, Petros; Papageorgiou, Sokratis G

    2012-01-01

    Hip fractures occur commonly and are a cause of disability for older adults and lead to increased dependence and requirements for social support. Dementia is one of the possible risk factors for falling and hip fracture, a potential source for complications during surgery and during the postoperative period, difficulties in rehabilitation and a risk factor for hip fracture reccurence. However, in previous studies of hip fracture patients, cognitive status has not been formally assessed during the inpatient stay and diagnosis was based only on previous history. Additionally, no previous studies have compared prevalence of dementia between elderly patients with hip fracture and patients with other surgical pathology. Our aim was to define whether dementia was more prevalent in older subjects with hip fracture than in other elderly patients undergoing surgery. In this study, we prospectively assessed all patients aged 68 and older admitted to our hospital for hip fracture surgery during a one year period and compared them with age and gender matched patients attending other surgical departments. 80 hip fracture patients and 80 controls were assessed for dementia. Dementia was common in both groups, presumably reflecting the advanced mean age of both groups and cognitive deterioration due to hospitalization-status. Dementia was significantly higher in the hip fracture group (85%) compared to the control group (61.5%; p=0.002). Dementia is very common in older patients admitted for surgery to a general hospital and extremely common in those with hip fracture. It seems that dementia is under diagnosed in elderly hospitalised patients. Our data confirm that dementia is a major risk factor for hip fracture in the elderly.

  4. Differential regional cerebral glucose metabolism in clinical syndromes of frontotemporal lobar degeneration: a study with FDG PET

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    Park, J. M.; Cho, S. S.; Na, D. L.; Lee, K. H.; Choi, Y.; Choe, Y. S.; Kim, B. T.; Kim, S. E. [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    2001-07-01

    Frontotemporal lobar degeneration( FTLD) is the third most common dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neurobehavioral syndromes can be produced by FTLD: frontotemporal dementia (FTD), frontotemporal dementia with motor neuron disease (MND), semantic dementia (SD), and progressive aphasia (PA). We investigated patterns of metabolic impairment in patient with FTLD presented with four different clinical syndromes. We analysed glucose metabolic patterns on FDG PET images obtained from 34 patients with a clinical diagnosis of FTLD (19 FTD, 6 MND, 6 SD, and 3 PA, according to a consensus criteria for clinical syndromes associated with FTLD) and 7 age-matched healthy controls using SPM99. Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral premotor are was shown in patients with MND. Patients with SD had metabolic deficit in the left posterior temporal cortex including Wernicke's area, while hypometabolism in the bilateral inferior frontal gyrus including Broca's area and left angular gyrus was seen in patients with PA. These metabolic patterns were well correlated with clinical features of FTLD syndromes. These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD.

  5. Increasing progranulin levels and blockade of the ERK1/2 pathway: upstream and downstream strategies for the treatment of progranulin deficient frontotemporal dementia.

    Science.gov (United States)

    Alquezar, Carolina; Esteras, Noemí; de la Encarnación, Ana; Moreno, Fermín; López de Munain, Adolfo; Martín-Requero, Ángeles

    2015-03-01

    Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder marked by mild-life onset and progressive changes in behavior, social cognition, and language. Loss-of-function progranulin gene (GRN) mutations are the major cause of FTLD with TDP-43 protein inclusions (FTLD-TDP). Disease-modifying treatments for FTLD-TDP are not available yet. Mounting evidence indicates that cell cycle dysfunction may play a pathogenic role in neurodegenerative disorders including FTLD. Since cell cycle re-entry of posmitotic neurons seems to precede neuronal death, it was hypothesized that strategies aimed at preventing cell cycle progression would have neuroprotective effects. Recent research in our laboratory revealed cell cycle alterations in lymphoblasts from FTLD-TDP patients carrying a null GRN mutation, and in PGRN deficient SH-SY5Y neuroblastoma cells, involving overactivation of the ERK1/2 signaling pathway. In this work, we have investigated the effects of PGRN enhancers drugs and ERK1/2 inhibitors, in these cellular models of PGRN-deficient FTLD. We report here that both restoring the PGRN content, by suberoylanilide hydroxamic acid (SAHA) or chloroquine (CQ), as blocking ERK1/2 activation by selumetinib (AZD6244) or MEK162 (ARRY-162), normalized the CDK6/pRb pathway and the proliferative activity of PGRN deficient cells. Moreover, we found that SAHA and selumetinib prevented the cytosolic TDP-43 accumulation in PGRN-deficient lymphoblasts. Considering that these drugs are able to cross the blood-brain barrier, and assuming that the alterations in cell cycle and signaling observed in lymphoblasts from FTLD patients could be peripheral signs of the disease, our results suggest that these treatments may serve as novel therapeutic drugs for FTLD associated to GRN mutations.

  6. Prosopagnosia: A rare presenting manifestation of frontotemporal lobar degeneration

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    George Arun

    2009-01-01

    Full Text Available Frontotemporal dementia is an important neurodegenerative disorder accounting for a significant proportion of dementia cases with onset before 60 years of age. Apart from the well recognized behavioral changes the disease has many other distinctive features like predominant language involvement alone or associated features of motor neuron disease or parkinsonism etc. which at times may be the presenting manifestation itself. In the following article we describe a rare presenting manifestation; prosopagnosia, in the setting of frontotemporal degeneration

  7. Semantic memory: Nouns and action verbs in cognitively unimpaired individuals and frontotemporal lobar degeneration

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    Leticia Lessa Mansur

    Full Text Available ABSTRACT Among the instruments to evaluate semantic memory, the Pyramids and Palm Trees (PPT and the Kissing and Dancing (KDT tests are widely used but none have a performance referential for cognitively normal and impaired Brazilian populations. Objective: [A] To study these two tests in a sample of young healthy Brazilian individuals living in São Paulo; [B] To apply the results to the evaluation of two cases diagnosed with frontotemporal lobar degeneration. Methods: We evaluated 50 normal participants (41 females and 9 males aged between 20-63 years, with schooling level of 14-20 years. In addition, two individuals diagnosed with frontotemporal lobar degeneration were examined, one with behavioral-variant frontotemporal dementia and the other with semantic dementia. Results: On the two tests, no effects of age, gender and schooling on the performance of normal individuals were observed. According to the performance of the sample of controls, scores below 46 points on the PPT and below 47 on the KDT are suggestive of deficits in semantic memory. The analyses of both cases indicated double dissociation in establishing associations between nouns and action verbs. Although the two patients had low scores on both tests, the patient with behavioral-variant frontotemporal dementia performed better on the PPT compared to the KDT, while the patient with semantic dementia showed the reverse, performing better on the KDT. Conclusion: The PPT and KDT are suitable tests for use in the Brazilian population, with minimal need for adjustments. They are applicable tools both for cognitive assessment and research in semantic memory. In the present study, we obtained representative values of performance for cognitively unimpaired individuals and demonstrated the utility of these instruments for cognitive assessment of patients with FTLD.

  8. Evaluative Conditioning with Facial Stimuli in Dementia Patients.

    Science.gov (United States)

    Blessing, Andreas; Zöllig, Jacqueline; Weierstall, Roland; Dammann, Gerhard; Martin, Mike

    2013-01-01

    We present results of a study investigating evaluative learning in dementia patients with a classic evaluative conditioning paradigm. Picture pairs of three unfamiliar faces with liked, disliked, or neutral faces, that were rated prior to the presentation, were presented 10 times each to a group of dementia patients (N = 15) and healthy controls (N = 14) in random order. Valence ratings of all faces were assessed before and after presentation. In contrast to controls, dementia patients changed their valence ratings of unfamiliar faces according to their pairing with either a liked or disliked face, although they were not able to explicitly assign the picture pairs after the presentation. Our finding suggests preserved evaluative conditioning in dementia patients. However, the result has to be considered preliminary, as it is unclear which factors prevented the predicted rating changes in the expected direction in the control group.

  9. Evaluative Conditioning with Facial Stimuli in Dementia Patients

    Directory of Open Access Journals (Sweden)

    Andreas Blessing

    2013-01-01

    Full Text Available We present results of a study investigating evaluative learning in dementia patients with a classic evaluative conditioning paradigm. Picture pairs of three unfamiliar faces with liked, disliked, or neutral faces, that were rated prior to the presentation, were presented 10 times each to a group of dementia patients (N = 15 and healthy controls (N = 14 in random order. Valence ratings of all faces were assessed before and after presentation. In contrast to controls, dementia patients changed their valence ratings of unfamiliar faces according to their pairing with either a liked or disliked face, although they were not able to explicitly assign the picture pairs after the presentation. Our finding suggests preserved evaluative conditioning in dementia patients. However, the result has to be considered preliminary, as it is unclear which factors prevented the predicted rating changes in the expected direction in the control group.

  10. Music recognition in frontotemporal lobar degeneration and Alzheimer disease.

    Science.gov (United States)

    Johnson, Julene K; Chang, Chiung-Chih; Brambati, Simona M; Migliaccio, Raffaella; Gorno-Tempini, Maria Luisa; Miller, Bruce L; Janata, Petr

    2011-06-01

    To compare music recognition in patients with frontotemporal dementia, semantic dementia, Alzheimer disease, and controls and to evaluate the relationship between music recognition and brain volume. Recognition of familiar music depends on several levels of processing. There are few studies about how patients with dementia recognize familiar music. Subjects were administered tasks that assess pitch and melody discrimination, detection of pitch errors in familiar melodies, and naming of familiar melodies. There were no group differences on pitch and melody discrimination tasks. However, patients with semantic dementia had considerable difficulty naming familiar melodies and also scored the lowest when asked to identify pitch errors in the same melodies. Naming familiar melodies, but not other music tasks, was strongly related to measures of semantic memory. Voxel-based morphometry analysis of brain magnetic resonance imaging showed that difficulty in naming songs was associated with the bilateral temporal lobes and inferior frontal gyrus, whereas difficulty in identifying pitch errors in familiar melodies correlated with primarily the right temporal lobe. The results support a view that the anterior temporal lobes play a role in familiar melody recognition, and that musical functions are affected differentially across forms of dementia.

  11. Clinical features of delusional jealousy in elderly patients with dementia.

    Science.gov (United States)

    Hashimoto, Mamoru; Sakamoto, Shinichi; Ikeda, Manabu

    2015-06-01

    Delusional jealousy is a psychotic syndrome characterized by a belief in the infidelity of one's spouse that reaches delusional intensity. Although delusional jealousy has been described in relation to organic psychosis, little is known concerning the actual role of delusional jealousy in dementia. The aim of the present study was to investigate the clinical features of delusional jealousy and possible mechanisms whereby delusional jealousy arises in patients with dementia. We studied 208 consecutive outpatients with dementia (diagnosis based on DSM-III-R criteria; mean [SD] age of 77.0 [8.0] years; study period: September 2011-August 2012). Delusional jealousy was defined as a false belief derived from a pathological jealousy that makes the patient believe that his or her spouse is unfaithful. The prevalence of delusional jealousy was compared between Alzheimer's disease, dementia with Lewy bodies, and vascular dementia. Patients with and without delusional jealousy were compared in terms of general characteristics. In addition, each patient with delusional jealousy and their primary caregivers were interviewed about the clinical features of the syndrome. Of the 208 patients with dementia, 18 (8.7%) showed delusional jealousy. The prevalence of delusional jealousy in patients who had dementia with Lewy bodies (26.3%) was significantly higher than that in patients with Alzheimer's disease (5.5%) (P delusional jealousy in regard to gender (P = 1.00), age (P = .81), educational attainment (P = .29), presence of other persons living with the couple (P = .22), and Mini-Mental State Examination score (P = .47). On the other hand, delusional jealousy was preceded by the onset of serious physical diseases in nearly half of the patients. Delusional jealousy resolved within 12 months after treatment in 15 of 18 patients (83%). Although delusional jealousy is a considerable problem in dementia, the prognosis of delusional jealousy in demented patients appears to be

  12. EEG and dementia indicators in AIDS patients' Rorschach test

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    G. Fernandes do Prado

    1994-09-01

    Full Text Available We studied the EEG and Rorschach test (RT of nineteen AIDS patients and eight normal people in the same age group. Eight patients presented slow alpha rhythms (8 to 9 Hz; three, not-slow alpha rhythms (>9 to 13Hz; and eight, beta rhythms in background activity. Paroxystic activity, characterized by diffuse theta or delta waves, was present in eleven patients. We observed Oberholzer syndrome (organic dementia diagnosed by RT in ten patients and Piotrowski syndrome (organic dementia diagnosed by RT in eleven patients; six presented both. When considering only the group of AIDS patients, we did not observe a significant relation among slow alpha rhythm, not-slow alpha rhythm and the presence of paroxystic activity with the above-mentioned syndromes. AIDS patients with slow alpha rhythms showed a significantly greater number of Piotrowski syndrome dementia indicators when compared to normal individuals or those with slow alpha rhythms. We did not observe the same with Oberholzer syndrome.

  13. Dementia

    Science.gov (United States)

    ... performing familiar tasks. People who have dementia may struggle with simple things, like getting dressed. They may ... to the visit with them. This lets you speak with the doctor in private. You can tell ...

  14. Dementia

    Science.gov (United States)

    ... Publication View Full Treatment Information View Hope Through Research Publication Definition Dementia is not a specific disease. It is a descriptive term for a collection of symptoms that can ...

  15. Psychotropic Polypharmacy in Patients with Dementia

    DEFF Research Database (Denmark)

    Nørgaard, Ane; Jensen-Dahm, Christina; Gasse, Christiane

    2017-01-01

    classes (psychotropic polypharmacy) may also pose a risk for patients. OBJECTIVE: To investigate the prevalence and predictors associated with use of psychotropic polypharmacy in patients with dementia. METHODS: A population-based study using nationwide registers. Patients with dementia were identified......,403) used at least one other psychotropic drug during the antipsychotic treatment period. Nursing home residency, number of non-psychotropic medications used in 2011, and prior psychiatric diagnosis were associated with psychotropic polypharmacy among antipsychotic drug users. The most frequent combination...... cause adverse events, and potential consequences for patients' safety call for further investigation....

  16. Epidemiological Survey of Frontotemporal Lobar Degeneration in Tottori Prefecture, Japan

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    Kenji Wada-Isoe

    2012-09-01

    Full Text Available Background: The prevalence of frontotemporal lobar degeneration (FTLD in Japan is unknown. An epidemiological survey study of FTLD was undertaken in Tottori Prefecture, a district in the western region of Japan. Methods: Hospitals in Tottori Prefecture were surveyed by a two-step questionnaire in 2010, and the prevalence of FTLD per 100,000 inhabitants was calculated using the actual number of patients and inhabitants in Tottori Prefecture on the prevalence day of October 1, 2010. Results: In this survey, 66 patients were diagnosed with FTLD. The subtypes of FTLD were as follows: 62 cases of frontotemporal dementia (FTD, 3 cases of progressive nonfluent aphasia, and 1 case of semantic dementia. Among the FTD cases, 5 cases were FTD with motor neuron disease and 1 case was FTD with parkinsonism linked to chromosome 17. The prevalence of FTD in the total population of Tottori Prefecture was 11.2 per 100,000 inhabitants. Based on these results, the prevalence of FTLD in Japan in 2008 was estimated to be 9.5 per 100,000 individuals. Conclusions: Our epidemiological survey results suggest that there are at least 12,000 FTLD patients in Japan, indicating that FTLD is not a rare disease.

  17. Pain assessment in patients with possible vascular dementia

    NARCIS (Netherlands)

    Scherder, EJA; Slaets, J; Deijen, JB; Gorter, Y; Ooms, ME; Ribbe, M; Vuijk, PJ; Feldt, K; van de Valk, M; Bouma, A; Sergeant, JA

    2003-01-01

    PREVIOUS studies comparing Alzheimer's disease (AD) patients with the normal elderly suggest that AD patients experience less pain. In the present study, pain reporting in 20 patients with possible vascular dementia (VaD) was compared to 20 nondemented elderly who had comparable pain conditions. It

  18. Anaesthesia for the patient with dementia undergoing outpatient surgery

    DEFF Research Database (Denmark)

    Funder, Kamilia S; Steinmetz, Jacob; Rasmussen, Lars S

    2009-01-01

    PURPOSE OF REVIEW: Dementia is common in elderly patients, and anaesthesiologists are increasingly challenged in managing these patients who are especially vulnerable. The aim of this article is to highlight some of the most important perioperative issues relating to demented patients, both...

  19. Dementia and delirium, the outcomes in elderly hip fracture patients

    Science.gov (United States)

    Mosk, Christina A; Mus, Marnix; Vroemen, Jos PAM; van der Ploeg, Tjeerd; Vos, Dagmar I; Elmans, Leon HGJ; van der Laan, Lijckle

    2017-01-01

    Background Delirium in hip fractured patients is a frequent complication. Dementia is an important risk factor for delirium and is common in frail elderly. This study aimed to extend the previous knowledge on risk factors for delirium and the consequences. Special attention was given to patients with dementia and delirium. Methods This is a retrospective cohort study performed in the Amphia Hospital, Breda, the Netherlands. A full electronic patient file system (Hyperspace Version IU4: Epic, Inc., Verona, WI, USA) was used to assess data between January 2014 and September 2015. All patients presented were aged ≥70 years with a hip fracture, who underwent surgery with osteosynthesis or arthroplasty. Patients were excluded in case of a pathological or a periprosthetic hip fracture, multiple traumatic injuries, and high-energy trauma. Patient and surgical characteristics were documented. Postoperative outcomes were noted. Delirium was screened using Delirium Observation Screening Scale and dementia was assessed from medical notes. Results Of a total of 566 included patients, 75% were females. The median age was 84 years (interquartile range: 9). Delirium was observed in 35%. Significant risk factors for delirium were a high American Society of Anesthesiology score, delirium in medical history, functional dependency, preoperative institutionalization, low hemoglobin level, and high amount of blood transfusion. Delirium was correlated with a longer hospital stay (P=0.001), increased association with complications (PPatients with dementia (N=168) had a higher delirium rate (57.7%, Ppatients with (34.0%) and without dementia (26.3%). Conclusion Elderly patients with a hip fracture are vulnerable for delirium, especially when the patient has dementia. Patients who underwent an episode of delirium were at increased risk for adverse outcomes. PMID:28331300

  20. Communication Problems Within Families With Patients With Dementia

    Directory of Open Access Journals (Sweden)

    Polina Balkanska

    2012-10-01

    Full Text Available Dementia in later age is an extreme hardship for the affected families. More than 90% of these patients in Bulgaria live with their families. The results from the conducted study pointed out that a big share of the specific problems of these families is related to the lack of communication skills on the part of the relatives of the patient. This was to a great extent due to the lack of information on the characteristics of the process of dementia as well as on the concurrent personality changes in the patient. This article reviews the main difficulties of the families in taking care of patients with dementia as well as clarifies appropriate psychological forms of support aimed at lowering the family distress originating from the disease.

  1. Frontotemporal cognitive function in X-linked spinal and bulbar muscular atrophy (SBMA): a controlled neuropsychological study of 20 patients.

    Science.gov (United States)

    Soukup, Georg Rüdiger; Sperfeld, Anne-Dorte; Uttner, Ingo; Karitzky, Jochen; Ludolph, Albert Christian; Kassubek, Jan; Schreiber, Herbert

    2009-11-01

    A cross-sectional neuropsychological study of cognitive functions in 20 male patients with genetically proven spinal and bulbar muscular atrophy (SBMA) was performed, with a comparison of their cognitive performance with that of 20 age- and education-matched control subjects. Neuropsychological assessment covered executive functioning, memory, and attentional control. The SBMA patients revealed deficits in verbal and non-verbal fluency as well as concept formation. Additionally, they showed significant memory deficits in all of the investigated domains of working memory, short-term and long-term memory. With respect to attentional control, the SBMA patients underperformed in relevant subtests, although performance differences did not reach significance overall. We conclude that fronto-temporal cognitive functions are impaired in SMBA, although at a subclinical level. Thus, functional deficits in SBMA are not confined to motor neurons but also affect extramotor networks.

  2. Neuropathology of frontotemporal lobar degeneration: A review

    Directory of Open Access Journals (Sweden)

    Valéria Santoro Bahia

    Full Text Available ABSTRACT Frontotemporal lobar degeneration (FTLD is the second most common cause of presenile dementia. Three main clinical variants are widely recognized within the FTLD spectrum: the behavioural variant of frontotemporal dementia (bvFTD, semantic dementia (SD and progressive non-fluent aphasia (PNFA. FTLD represents a highly heterogeneous group of neurodegenerative disorders which are best classified according to the main protein component of pathological neuronal and glial inclusions. The most common pathological class of FTLD is associated with the TDP-43 protein (FTLD-TDP, while FTLD-Tau is considered slightly less common while the FTLD-FUS (Fused in sarcoma protein pathology is rare. In this review, these three major pathological types of FTLD are discussed.

  3. Dementia and delirium, the outcomes in elderly hip fracture patients.

    Science.gov (United States)

    Mosk, Christina A; Mus, Marnix; Vroemen, Jos Pam; van der Ploeg, Tjeerd; Vos, Dagmar I; Elmans, Leon Hgj; van der Laan, Lijckle

    2017-01-01

    Delirium in hip fractured patients is a frequent complication. Dementia is an important risk factor for delirium and is common in frail elderly. This study aimed to extend the previous knowledge on risk factors for delirium and the consequences. Special attention was given to patients with dementia and delirium. This is a retrospective cohort study performed in the Amphia Hospital, Breda, the Netherlands. A full electronic patient file system (Hyperspace Version IU4: Epic, Inc., Verona, WI, USA) was used to assess data between January 2014 and September 2015. All patients presented were aged ≥70 years with a hip fracture, who underwent surgery with osteosynthesis or arthroplasty. Patients were excluded in case of a pathological or a periprosthetic hip fracture, multiple traumatic injuries, and high-energy trauma. Patient and surgical characteristics were documented. Postoperative outcomes were noted. Delirium was screened using Delirium Observation Screening Scale and dementia was assessed from medical notes. Of a total of 566 included patients, 75% were females. The median age was 84 years (interquartile range: 9). Delirium was observed in 35%. Significant risk factors for delirium were a high American Society of Anesthesiology score, delirium in medical history, functional dependency, preoperative institutionalization, low hemoglobin level, and high amount of blood transfusion. Delirium was correlated with a longer hospital stay (P=0.001), increased association with complications (Pdelirium rate (57.7%, Pdelirium, especially when the patient has dementia. Patients who underwent an episode of delirium were at increased risk for adverse outcomes.

  4. Trajectories of cognitive decline in different types of dementia.

    Science.gov (United States)

    Smits, L L; van Harten, A C; Pijnenburg, Y A L; Koedam, E L G E; Bouwman, F H; Sistermans, N; Reuling, I E W; Prins, N D; Lemstra, A W; Scheltens, P; van der Flier, W M

    2015-04-01

    To investigate trajectories of cognitive decline in patients with different types of dementia compared to controls in a longitudinal study. In 199 patients with Alzheimer's disease (AD), 10 with vascular dementia (VaD), 26 with dementia with Lewy bodies (DLB), 20 with behavioural variant frontotemporal dementia (bvFTD), 15 with language variant frontotemporal dementia (lvFTD) and 112 controls we assessed five cognitive domains: memory, language, attention, executive and visuospatial functioning, and global cognition (Mini-Mental State Examination, MMSE). All subjects had at least two neuropsychological assessments (median 2, range 2-7). Neuropsychological data were standardized into z scores using baseline performance of controls as reference. Linear mixed models (LMMs) were used to estimate baseline cognitive functioning and cognitive decline over time for each group, adjusted for age, gender and education. At baseline, patients with dementia performed worse than controls in all cognitive domains (p cognitive domains (p cognitive domain except language and global cognition. bvFTD showed rapid decline in memory, language, attention and executive functioning (all p cognitive trajectories of different types of dementia. These estimations of natural disease course have important value for the design of clinical trials as neuropsychological measures are increasingly being used as outcome measures.

  5. Behind the Veil: Mandala Drawings by Dementia Patients.

    Science.gov (United States)

    Couch, Janet Beaujon

    1997-01-01

    Examines the Mandala (circular) drawings of elderly patients diagnosed with dementia in order to explore the drawings' role in artmaking and patients' internal processes. Categorized drawings using the MARI Card Test (a projective psychological instrument). Describes the six MARI stages drawn most frequently and colors used most often. (RJM)

  6. [Handling of patients with dementia--scenario 2050].

    Science.gov (United States)

    Jordan, Wolfgang

    2014-07-01

    The relationship between social attitudes, normative ethics, health care elite's and individual failure has been highlighted in a scenario for patients with dementia. Inhuman abuse may be protected by sense of responsibility, duty to social being, inclusion of psychiatric patients, and the foundation of human dignity.

  7. Behind the Veil: Mandala Drawings by Dementia Patients.

    Science.gov (United States)

    Couch, Janet Beaujon

    1997-01-01

    Examines the Mandala (circular) drawings of elderly patients diagnosed with dementia in order to explore the drawings' role in artmaking and patients' internal processes. Categorized drawings using the MARI Card Test (a projective psychological instrument). Describes the six MARI stages drawn most frequently and colors used most often. (RJM)

  8. Management strategies for problem behaviors in the patient with dementia.

    Science.gov (United States)

    Lehninger, F W; Ravindran, V L; Stewart, J T

    1998-04-01

    Psychiatric and behavioral problems are present in most patients with dementia and are usually the clinician's main focus of management. Differential diagnosis of these problems can be challenging, but the effort is essential for planning appropriate therapy. Pharmacologic interventions are available for treatment of depression, agitation, aggression, psychotic symptoms, wandering, and sleep disorders. Given the less than favorable risk-benefit ratio of most psychotropic drugs in the population of older patients with dementia, the importance of nonpharmacologic strategies and limiting treatment goals should not be overlooked.

  9. Computed tomography in patients with dementia probably due to toxic encephalopathy.

    Science.gov (United States)

    Skjødt, T; Torfing, K F; Teisen, H

    1988-01-01

    Computed tomography (CT) was performed in 181 patients with dementia probably caused by organic solvents. No treatable causes of dementia were revealed. All but one of the patients had dementia symptoms for more than one year. Only three patients had focal neurologic signs. No indication for cranial CT was found in this group of patients, owing to the fact that no treatable causes of dementia were revealed.

  10. Computed tomography in patients with dementia probably due to toxic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Skjoedt, T.; Torfing, K.F.; Teisen, H.

    Computed tomography (CT) was performed in 181 patients with dementia probably caused by organic solvents. No treatable causes of dementia were revealed. All but one of the patients had dementia symptoms for more than one year. Only three patients had focal neurologic signs. No indication for cranial CT was found in this group of patients, owing to the fact that no treatable causes of dementia were revealed.

  11. Diagnosis and Management of Patients with Dementia

    Institute of Scientific and Technical Information of China (English)

    Jean-Mare Orgogozo

    2001-01-01

    @@ Dementia is becoming a major concern worldwide because its prevalence and incidence rise exponentially with increasing age. The prevalence rates double with every 5 years of age, from about 5% (4-12%depending on the studies) in those aged 65 and older to about 40% over 90[1], and up to 58% in those 95 and older[2]. The annual incidence rate of dementia is 2.2% per year over age 65[3]. According to 1996 United Nations projections, the number of individuals ~ed 65 and older in the more developed countries will increase from 169 million (14.2% of the population) to 287 million (24. 7% of the population)[3]. Besides the huge human and social costs, the economic burden of dementia is enormous in countries with a long lifeexpectancy[3], both from direct costs, i.e., those that result in actual monetary expenditures, such as hospital care, physician visits, medications, home health care workers or institutional care and indirect costs, i.e.,those that do not result in actual monetary expenditures, such as time spouses or other caregivers spend helping and caring.

  12. Acupuncture on Gnosia and Acetylcholinesterase in Senile Dementia Patients

    Institute of Scientific and Technical Information of China (English)

    TANG Yong; YU Shu-guang; CHEN Jin; ZHANG Wei

    2003-01-01

    Purpose To observe the effect of acupuncture on gnosia and acetylcholinesterase in patients with senile dementia. Methods Eight patients diagnosed with mild or moderate senile dementia were treated by acupuncture of Sishencong ( Ex-HN 1 ), Shenmen ( HT 7) and Taixi ( KI 3) for I month; gnosia was evaluated by Mini-mental state examination before and after the treatment; plasma acetylcholin esterase activity was measured by flourier before and after the treatment. Results There was a significant difference in gnosia between pre- and post--treatment with acupuncture (P<0.01); there was no significant difference in acetyl- cholinesterase activity between pre- and posttreatment ( P>0.05 ). Conclusion Acupuncture has a certain improving effect on gnosia in senile dementia;one month's acupuncture treatment had little effect on plasma acetyl-cholinesterase activity.

  13. Dementia and delirium, the outcomes in elderly hip fracture patients

    Directory of Open Access Journals (Sweden)

    Mosk CA

    2017-03-01

    Full Text Available Christina A Mosk,1 Marnix Mus,1 Jos PAM Vroemen,1 Tjeerd van der Ploeg,2 Dagmar I Vos,1 Leon HGJ Elmans,3 Lijckle van der Laan1 1Department of Surgery, Amphia Hospital, Breda, 2Department of Public Health, Erasmus MC–University Medical Center, Rotterdam, 3Department of Orthopedic Surgery, Amphia Hospital, Breda, the Netherlands Background: Delirium in hip fractured patients is a frequent complication. Dementia is an important risk factor for delirium and is common in frail elderly. This study aimed to extend the previous knowledge on risk factors for delirium and the consequences. Special attention was given to patients with dementia and delirium.Methods: This is a retrospective cohort study performed in the Amphia Hospital, Breda, the Netherlands. A full electronic patient file system (Hyperspace Version IU4: Epic, Inc., Verona, WI, USA was used to assess data between January 2014 and September 2015. All patients presented were aged ≥70 years with a hip fracture, who underwent surgery with osteosynthesis or arthroplasty. Patients were excluded in case of a pathological or a periprosthetic hip fracture, multiple traumatic injuries, and high-energy trauma. Patient and surgical characteristics were documented. Postoperative outcomes were noted. Delirium was screened using Delirium Observation Screening Scale and dementia was assessed from medical notes.Results: Of a total of 566 included patients, 75% were females. The median age was 84 years (interquartile range: 9. Delirium was observed in 35%. Significant risk factors for delirium were a high American Society of Anesthesiology score, delirium in medical history, functional dependency, preoperative institutionalization, low hemoglobin level, and high amount of blood transfusion. Delirium was correlated with a longer hospital stay (P=0.001, increased association with complications (P<0.001, institutionalization (P<0.001, and 6-month mortality (P<0.001. Patients with dementia (N=168 had a

  14. Improving activity and engagement for patients with dementia.

    Science.gov (United States)

    Bray, Jennifer; Evans, Simon; Bruce, Mary; Carter, Christine; Brooker, Dawn; Milosevic, Sarah; Thompson, Rachel; Hutt, Louise

    2015-10-01

    This is the second in a short series that presents case study examples of the positive work achieved by trusts that participated in the Royal College of Nursing's development programme to improve dementia care in acute hospitals. Staff often think that there is insufficient time to get to know patients and carers, especially with large and challenging workloads. Combined with a lack of activities and stimulation for patients with dementia in hospital, this can result in poor engagement and a disconnect between staff and patients. To improve these relationships and give staff more time with patients, Cambridge University Hospitals NHS Foundation Trust has introduced bay nursing for patients with dementia, where one nurse is responsible for monitoring a bay alongside a healthcare assistant for an entire shift. Part of Betsi Cadwaladr University Health Board, Glan Clwyd Hospital in north Wales has focused on improving stimulation by creating an activity room with a specially trained activity worker, providing a relaxed and friendly setting where patients with dementia can take part in a range of activities and have lunch together.

  15. Barriers, motivators, and facilitators of physical activity in dementia patients : A systematic review

    NARCIS (Netherlands)

    van Alphen, Helena J. M.; Hortobagyi, Tibor; van Heuvelen, Marieke J. G.

    2016-01-01

    Purpose: Physical activity (PA) has the potential to slow the progression of dementia patients' cognitive and physical decline. A better understanding of the factors that facilitate or hamper dementia patients' PA participation will increase the success rate of implementing PA in dementia patients'

  16. Barriers, motivators, and facilitators of physical activity in dementia patients : A systematic review

    NARCIS (Netherlands)

    van Alphen, Helena J. M.; Hortobagyi, Tibor; van Heuvelen, Marieke J. G.

    2016-01-01

    Purpose: Physical activity (PA) has the potential to slow the progression of dementia patients' cognitive and physical decline. A better understanding of the factors that facilitate or hamper dementia patients' PA participation will increase the success rate of implementing PA in dementia patients'

  17. Coprophagia and Entomophagia in a Patient with Alcohol Related Dementia

    Directory of Open Access Journals (Sweden)

    João B. Fonseca

    2017-01-01

    Full Text Available Coprophagia and entomophagia are two phenomena not commonly reported in the medical literature and their occurrence is usually associated with mental disorders. We present the case of a 59-year-old man with a history of alcohol abuse who was evaluated due to cognitive deterioration and disturbed eating habits including feces and living insects. Organic causes were ruled out and an important cognitive impairment became evident on neuropsychological formal test. The behavior remitted after antipsychotic pharmacologic therapy and alcohol detoxification, leaving the diagnostic impression of alcohol related dementia. This report shows a rare association of these two conditions in a patient with dementia.

  18. Patients with rosacea have increased risk of dementia

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Hansen, Peter R; Gislason, G. H.

    2016-01-01

    Objective Rosacea is a common chronic inflammatory skin disorder where upregulation of matrix metalloproteinases (MMPs) and antimicrobial peptides (AMPs) is observed. Notably, inflammation, MMPs, and AMPs are also involved in the etiopathogenesis of neurodegenerative disorders including certain...... forms of dementia such as Alzheimer disease (AD). Based on several clinical observations, we investigated the association between rosacea and dementia, including AD in Danish registers. Methods All Danish citizens aged ≥18 years between January 1, 1997 and December 31, 2012 were linked at the individual...... level through administrative registers. Cox regression was used to calculate unadjusted and adjusted hazard ratios (HRs). Results The study comprised a total of 5,591,718 individuals, including 82,439 patients with rosacea. A total of 99,040 individuals developed dementia (any form) in the study period...

  19. [Therapeutic massage on behavioral disturbances of elderly patients with dementia].

    Science.gov (United States)

    Barquilla Ávila, Carolina; Rodríguez-Mansilla, Juan

    2015-12-01

    To know the efficacy of therapeutic massage on behavioral disturbances of elderly patients with dementia. Literature review. The literature search was done in six scientific databases: PubMed, Cochrane Library Plus, PEDro, Dialnet, Scopus and CSIC, between 1983 and 2013. The search terms were "massage", "dementia", "therapy", "behavior disorders" and "Alzheimer". Of the 496 articles analyzed, 11 scientific articles have met the selection criteria. Inclusion criteria were: clinical trials, published in English or Spanish, which had analyzed the effects of massage therapy on altered behaviors in people with dementia. The variables were massage benefits, type of massage and massage lubricant. Their authors use different massage techniques (effleurage, pétrissage, pressures, frictions and kneading), obtain better conduct disorders (aggression, anxiety, agitation, and resistance to care) of elderly. The therapeutic massage can be a complementary treatment in the rehabilitation program for better behavior disorders. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  20. [Canopy-enclosed bed for dementia patients with behavioural problems

    NARCIS (Netherlands)

    Molleman, P.W.; Kesteren, J.B. van; Ubink-Bontekoe, C.J.; Zoomer-Hendriks, M.P.; Wetzels, R.B.

    2015-01-01

    Patients with dementia almost all have one or more symptoms of problem behaviour. This problem behaviour includes a wide range of symptoms including depression, anxiety and apathy, and behavioural problems such as aggression, general restlessness, compulsion to walk, disinhibition and calling, and p

  1. Nursing diagnoses, interventions and outcomes for institutionalized patients with dementia

    Directory of Open Access Journals (Sweden)

    Paula,Escalada-Hernández

    2015-04-01

    Full Text Available Aim: To describe the most frequent NANDA-I nursing diagnoses and the associated NIC in-terventions and NOC outcomes used in nursing care plans for a sample of institutionalized patients with dementia. Methods: Descriptive analyses were performed based on a subsample from a multicentric and cross-sectional study. Data were obtained retrospectively from the electronic patient records and included socio-demografic details, NANDA-I, NIC and NOC labels and the HoNOS scale. Results: In total, 108 patients diagnosed with dementia were included. The nine most prevalent NANDA-I nursing diagnoses and the NOC outcomes and NIC interventions linked to them were presented. According to HoNOS scale, the most common problems among elders with dementia were cognitive problems and problems with activities of daily living, with relationships and related to physical illness or disability. Conclusions: Thisstudy identified patterns of nursing care for institutionalized patients with dementia where the most prevalent nursing diagnoses, interventions and outcomes addressed a wide range of functional, psychosocial and physiological care needs.

  2. Enteral nutrition in patients with dementia and stroke.

    Science.gov (United States)

    Freeman, Cecilia; Ricevuto, Ashleigh; DeLegge, Mark H

    2010-03-01

    Patients suffering from dementia or significant cognitive impairment (SCI) due to neurologic injury routinely receive percutaneous endoscopic gastrostomy (PEG) due to swallowing difficulty or lack of appetite. This review discusses current data and opinion regarding the risks and benefits of PEG in these populations. The current data regarding PEG placement in patients with dementia or SCI due to neurologic injury do not confirm either improvement or worsening of survival. Significant risk factors for poor prognosis after PEG include sex, hypoalbuminemia, age, chronic heart failure, and subtotal gastrectomy. Complications associated with enteral nutrition are minor and easily controlled when managed by a nutritional team. Alternative options for feeding elderly demented patients are available for family members considering PEG. In contrast to previously published data regarding worse clinical outcomes in the dementia and SCI populations receiving PEG, recent data suggest that clinical outcomes in this population are no different than in other patient populations receiving PEG. A prospective, randomized study is needed to ascertain whether PEG is appropriate and beneficial in the dementia/SCI populations.

  3. Dementia and delirium, the outcomes in elderly hip fracture patients

    NARCIS (Netherlands)

    Mosk, C.A. (Christina A.); Mus, M. (Marnix); Vroemen, J.P.A.M. (Jos P. A. M.); T. van der Ploeg (Tjeerd); D.I. Vos (Dagmar); Elmans, L.H.G.J. (Leon H. G. J.); L. van der Laan (Lyckle)

    2017-01-01

    textabstractBackground: Delirium in hip fractured patients is a frequent complication. Dementia is an important risk factor for delirium and is common in frail elderly. This study aimed to extend the previous knowledge on risk factors for delirium and the consequences. Special attention was given to

  4. Christianity and Resilience as Experienced by Caregivers of Dementia Patients

    Science.gov (United States)

    Lackey, Steven L.

    2014-01-01

    The purpose of this study was to examine the role and relationship of the practice of Christian beliefs and resilience in the context of dementia patient caregivers' lives. The guiding question was "What is the relational nature of the practice of Christian beliefs and resilience in the lived experiences of caregivers of dementia…

  5. [Snoezelen and animal-assisted therapy in dementia patients].

    Science.gov (United States)

    Javelot, Hervé; Antoine-Bernard, Emilie; Garat, Jennifer; Javelot, Thierry; Weiner, Luisa; Mervelay, Véroníque

    2012-01-01

    A number of non medication-based methods of nursing care for geriatric patients have been developed over recent decades to treat non cognitive symptoms associated with dementia. Among these, Snoezelen rooms for multisensory behavioural therapy and animal-assisted therapy emerge as innovative strategies which could potentially complement other more frequently developed methods such as physical activity.

  6. Topical review: orofacial pain in dementia patients: a diagnostic challenge

    NARCIS (Netherlands)

    Lobbezoo, F.; Weijenberg, R.A.F.; Scherder, E.J.A.

    2011-01-01

    This article presents a comprehensive review of the literature on the diagnosis of pain in the orofacial region of patients suffering from a cognitive impairment or a dementia. This review was based on a literature search yielding 74 papers, most of which dealt with the assessment of pain in general

  7. Topical review: orofacial pain in dementia patients: a diagnostic challenge

    NARCIS (Netherlands)

    Lobbezoo, F.; Weijenberg, R.A.F.; Scherder, E.J.A.

    2011-01-01

    This article presents a comprehensive review of the literature on the diagnosis of pain in the orofacial region of patients suffering from a cognitive impairment or a dementia. This review was based on a literature search yielding 74 papers, most of which dealt with the assessment of pain in general

  8. Measurement of speech parameters in casual speech of dementia patients

    NARCIS (Netherlands)

    Ossewaarde, Roelant; Jonkers, Roel; Jalvingh, Fedor; Bastiaanse, Yvonne

    Measurement of speech parameters in casual speech of dementia patients Roelant Adriaan Ossewaarde1,2, Roel Jonkers1, Fedor Jalvingh1,3, Roelien Bastiaanse1 1CLCG, University of Groningen (NL); 2HU University of Applied Sciences Utrecht (NL); 33St. Marienhospital - Vechta, Geriatric Clinic Vechta

  9. Factors Associated with a Depressive Disorder in Alzheimer's Disease Are Different from Those Found for Other Dementia Disorders

    Science.gov (United States)

    Barca, Maria Lage; Engedal, Knut; Laks, Jerson; Selbaek, Geir

    2012-01-01

    Background This study explores factors associated with depression in Alzheimer's disease (AD) compared with mild cognitive impairment (MCI) and other dementia disorders. Method In a prospective study we included 195 patients: 31 with MCI, 112 with AD and 52 with other dementias. Results According to the ICD-10 and the DSM-IV criteria, 88 (44.1%) and 59 (30.3%), respectively, had a depressive disorder. An adjusted multiple regression analysis showed that previous depression (p depression in AD patients. Severity of dementia (p depressive disorder in a group of patients with frontotemporal dementia, vascular dementia, or dementia due to Lewy Body disease or Parkinson's disease. Conclusion We found different factors associated with a depressive disorder in AD compared to those found for other dementia disorders. PMID:22479262

  10. Nuclear inclusions mimicking poly(A)-binding protein nuclear 1 inclusions in a case of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia with a novel mutation in the valosin-containing protein gene.

    Science.gov (United States)

    Matsubara, Shiro; Shimizu, Toshio; Komori, Takashi; Mori-Yoshimura, Madoka; Minami, Narihiro; Hayashi, Yukiko K

    2016-07-01

    A middle-aged Japanese man presented with slowly progressive asymmetric weakness of legs and arm but had neither ptosis nor dysphagia. He had a family history of similar condition suggestive of autosomal dominant inheritance. A muscle biopsy showed mixture of neurogenic atrophy and myopathy with rimmed vacuoles. Furthermore we found intranuclear inclusions that had a fine structure mimicking that of inclusions reported in oculopharyngeal muscular dystrophy (OPMD). Immunohistochemical staining for polyadenylate-binding nuclear protein 1, which is identified within the nuclear inclusions of OPMD, demonstrated nuclear positivity in this case. However, OPMD was thought unlikely based on the clinical features and results of genetic analyses. Instead, a novel mutation in valosin-containing protein, c.376A>T (p.Ile126Phe), was revealed. A diagnosis of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia was made. This is the first report of polyadenylate-binding nuclear protein 1-positive nuclear inclusions in the muscle of this condition.

  11. Linking white matter integrity loss to associated cortical regions using structural connectivity information in Alzheimer's disease and fronto-temporal dementia: the Loss in Connectivity (LoCo) score.

    Science.gov (United States)

    Kuceyeski, Amy; Zhang, Yu; Raj, Ashish

    2012-07-16

    It is well known that gray matter changes occur in neurodegenerative diseases like Alzheimer's (AD) and fronto-temporal dementia (FTD), and several studies have investigated their respective patterns of atrophy progression. Recent work, however, has revealed that diffusion MRI that is able to detect white matter integrity changes may be an earlier or more sensitive biomarker in both diseases. However, studies that examine white matter changes only are limited in that they do not provide the functional specificity of GM region-based analysis. In this study, we develop a new metric called the Loss in Connectivity (LoCo) score that gives the amount of structural network disruption incurred by a gray matter region for a particular pattern of white matter integrity loss. Leveraging the relative strengths of WM and GM markers, this metric links areas of WM integrity loss to their connected GM regions as a first step in understanding their functional implications. The LoCo score is calculated for three groups: 18AD, 18 FTD, and 19 age-matched normal controls. We show significant correlations of the LoCo with the respective atrophy patterns in AD (R=0.51, p=2.2 × 10(-9)) and FTD (R=0.49, p=2.5 × 10(-8)) for a standard 116 region gray matter atlas. In addition, we demonstrate that the LoCo outperforms a measure of gray matter atrophy when classifying individuals into AD, FTD, and normal groups.

  12. Agraphia in Bulbar-Onset Amyotrophic Lateral Sclerosis: Not Merely a Consequence of Dementia or Aphasia

    Science.gov (United States)

    Ichikawa, Hiroo; Takahashi, Nobuyoshi; Hieda, Soutaro; Ohno, Hideki; Kawamura, Mitsuru

    2008-01-01

    The clinical significance and characteristics of writing errors in bulbar-onset amyotrophic lateral sclerosis (ALS) are not clear. We retrospectively investigated writing samples in 19 patients with bulbar-onset ALS without preceding extra-motor symptoms. Co-development of dementia and/or aphasia was also explored and single photon emission computed tomography (SPECT) images of the brain were reviewed. As a result, a high prevalence of writing errors (15 of the 19 patients) was found. Of note were isolated writing errors with neither dementia nor aphasia verified in 2 patients whose dysarthria was mild enough to evaluate spoken language. The remaining 13 patients also showed agraphia, but either dysarthria was too severe to evaluate aphasia or frontotemporal dementia (FTD)-like features co-existed. Of these patients, one who initially lacked dementia subsequently developed FTD-like features. The frequent writing errors were omission or substitution of kana letters and syntactic errors. SPECT images showed bilateral or left-side dominant hypoperfusion in the frontotemporal lobes as a consistent feature. These results show that patients with bulbar-onset ALS frequently exhibit agraphic writing errors and that these are not merely consequences of dementia or aphasia. However, these writing errors may indicate the involvement of frontotemporal language-related areas beyond the primary motor cortex. PMID:19641246

  13. Development of a caregiver burden questionnaire for the patients with dementia in Iran

    Directory of Open Access Journals (Sweden)

    Ibrahim Abdollahpour

    2010-01-01

    Conclusions: The new tool has good reliability and validity suit-able to Iranian dementia patients and their caregivers′ culture. Researchers can use this tool to monitor the pressure mounted on dementia caregivers and to assess interventions in this group.

  14. Pain medication and global cognitive functioning in dementia patients with painful conditions

    NARCIS (Netherlands)

    Plooij, B.; Spek, K. van der; Scherder, E.J.

    2012-01-01

    BACKGROUND: Dementia patients are at an increased risk for undertreatment of pain, compared with older people without dementia, suggesting a relationship between pain medication prescription and cognitive functioning. Studies on a possible relationship between pain medication and cognitive functioni

  15. Weight Loss in Patients with Dementia: Considering the Potential Impact of Pharmacotherapy

    NARCIS (Netherlands)

    Franx, B.A.; Arnoldussen, I.A.C.; Kiliaan, A.J.; Gustafson, D.R.

    2017-01-01

    Unintentional body weight loss is common in patients with dementia and is linked to cognitive impairment and poorer disease outcomes. It is proposed that some dementia medications with market approval, while aiming to improve cognitive and functional outcomes of a patient with dementia, are associat

  16. Prediction of dementia in primary care patients.

    Directory of Open Access Journals (Sweden)

    Frank Jessen

    Full Text Available BACKGROUND: Current approaches for AD prediction are based on biomarkers, which are however of restricted availability in primary care. AD prediction tools for primary care are therefore needed. We present a prediction score based on information that can be obtained in the primary care setting. METHODOLOGY/PRINCIPAL FINDINGS: We performed a longitudinal cohort study in 3.055 non-demented individuals above 75 years recruited via primary care chart registries (Study on Aging, Cognition and Dementia, AgeCoDe. After the baseline investigation we performed three follow-up investigations at 18 months intervals with incident dementia as the primary outcome. The best set of predictors was extracted from the baseline variables in one randomly selected half of the sample. This set included age, subjective memory impairment, performance on delayed verbal recall and verbal fluency, on the Mini-Mental-State-Examination, and on an instrumental activities of daily living scale. These variables were aggregated to a prediction score, which achieved a prediction accuracy of 0.84 for AD. The score was applied to the second half of the sample (test cohort. Here, the prediction accuracy was 0.79. With a cut-off of at least 80% sensitivity in the first cohort, 79.6% sensitivity, 66.4% specificity, 14.7% positive predictive value (PPV and 97.8% negative predictive value of (NPV for AD were achieved in the test cohort. At a cut-off for a high risk population (5% of individuals with the highest risk score in the first cohort the PPV for AD was 39.1% (52% for any dementia in the test cohort. CONCLUSIONS: The prediction score has useful prediction accuracy. It can define individuals (1 sensitively for low cost-low risk interventions, or (2 more specific and with increased PPV for measures of prevention with greater costs or risks. As it is independent of technical aids, it may be used within large scale prevention programs.

  17. New Perspective on Parkinsonism in Frontotemporal Lobar Degeneration

    Directory of Open Access Journals (Sweden)

    Hee Kyung Park

    2013-04-01

    Full Text Available Frontotemporal dementia (FTD is the second most common type of presenile dementia. Three clinical prototypes have been defined; behavioral variant FTD, semantic dementia, and progressive nonfluent aphasia. Progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease may possess clinical and pathological characteristics that overlap with FTD, and it is possible that they may all belong to the same clinicopathological spectrum. Frontotemporal lobar degeneration (FTLD is a clinicopathological syndrome that encompasses a heterogenous group of neurodegenerative disorders. Owing to the advancement in the field of molecular genetics, diagnostic imaging, and pathology, FTLD has been the focus of great interest. Nevertheless, parkinsonism in FTLD has received relatively less attention. Parkinsonism is found in approximately 20–30% of patients in FTLD. Furthermore, parkinsonism can be seen in all FTLD subtypes, and some patients with familial and sporadic FTLD can present with prominent parkinsonism. Therefore, there is a need to understand parkinsonism in FTLD in order to obtain a better understanding of the disease. With regard to the clinical characteristics, the akinetic rigid type of parkinsonism has predominantly been described. Parkinsonism is frequently observed in familial FTD, more specifically, in FTD with parkinsonism linked to chromosome 17q (FTDP-17. The genes associated with parkinsonism are microtubule associated protein tau (MAPT, progranulin (GRN or PGRN, and chromosome 9 open reading frame 72 (C9ORF72 repeat expansion. The neural substrate of parkinsonism remains to be unveiled. Dopamine transporter (DAT imaging revealed decreased uptake of DAT, and imaging findings indicated atrophic changes of the basal ganglia. Parkinsonism can be an important feature in FTLD and, therefore, increased attention is needed on the subject.

  18. Theory of mind impairments in patients with semantic dementia.

    Science.gov (United States)

    Duval, Céline; Bejanin, Alexandre; Piolino, Pascale; Laisney, Mickael; de La Sayette, Vincent; Belliard, Serge; Eustache, Francis; Desgranges, Béatrice

    2012-01-01

    Semantic dementia is characterized by semantic deficits and behavioural abnormalities that occur in the wake of bilateral inferolateral and predominantly left-sided anterior temporal lobe atrophy. The temporal poles have been shown to be involved in theory of mind, namely the ability to ascribe cognitive and affective mental states to others that regulates social interactions by predicting and interpreting human behaviour. However, very few studies have examined theory of mind in semantic dementia. In this study, we investigated both cognitive and affective theory of mind in a group of patients with semantic dementia, using separate objective and subjective assessment tasks. Results provided objective evidence of an impact of semantic dementia on cognitive and affective theory of mind, consistent with the patients' atrophy in the left temporal lobe and hypometabolism in the temporal lobes and the medial frontal cortex. However, the subjective assessment of theory of mind suggested that awareness of the affective but not cognitive theory of mind deficit persists into the moderate stage of the disease.

  19. Opening up the DNA methylome of dementia.

    Science.gov (United States)

    Delgado-Morales, R; Esteller, M

    2017-01-03

    Dementia is a complex clinical condition characterized by several cognitive impairments that interfere with patient independence in executing everyday tasks. Various neurodegenerative disorders have dementia in common among their clinical manifestations. In addition, these diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies and frontotemporal dementia, share molecular alterations at the neuropathological level. In recent years, the field of neuroepigenetics has expanded massively and it is now clear that epigenetic processes, such as DNA methylation, are mechanisms involved in both normal and pathological brain function. Despite the persistent methodological and conceptual caveats, it has been reported that several genes fundamental to the development of neurodegenerative disorders are deregulated by aberrant methylation patterns of their promoters, and even common epigenetic signatures for some dementia-associated pathologies have been identified. Therefore, understanding the epigenetic mechanisms that are altered in dementia, especially those associated with the initial phases, will allow us not only to understand the etiopathology of dementia and its progression but also to design effective therapies to reduce this global public health problem. This review provides an in-depth summary of our current knowledge about DNA methylation in dementia, focusing exclusively on the analyses performed in human brain.Molecular Psychiatry advance online publication, 3 January 2017; doi:10.1038/mp.2016.242.

  20. Risk factors and hospitalization costs of Dementia patients: Examining race and gender variations

    Directory of Open Access Journals (Sweden)

    Baqar Husaini

    2015-01-01

    Full Text Available Aims: To examine the variation in risk factors and hospitalization costs among four elderly dementia cohorts by race and gender. Materials and Methods: The 2008 Tennessee Hospital Discharged database was examined. The prevalence, risk factors and cost of inpatient care of dementia were examined for individuals aged 65 years and above, across the four race gender cohorts - white males (WM, black males (BM, white females (WF, and black females (BF. Results: 3.6% of patients hospitalized in 2008 had dementia. Dementia was higher among females than males, and higher among blacks than whites. Further, BF had higher prevalence of dementia than WF; similarly, BM had a higher prevalence of dementia than WM. Overall, six risk factors were associated with dementia for the entire sample including HTN, DM, CKD, CHF, COPD, and stroke. These risk factors varied slightly in predicting dementia by race and gender. Hospital costs were 14% higher among dementia patients compared to non-dementia patients. Conclusions: There exist significant race and gender disparities in prevalence of dementia. A greater degree of co-morbidity, increased duration of hospital stay, and more frequent hospitalizations, may result in a higher cost of inpatient dementia care. Aggressive management of risk factors may subsequently reduce stroke and cost of dementia care, especially in the black population. Race and gender dependent milestones for management of these risk factors should be considered.

  1. Neuronal ubiquitinated intranuclear inclusions in familial and non-familial frontotemporal dementia of the motor neuron disease type associated with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bigio, Eileen H; Johnson, Nancy A; Rademaker, Alfred W; Fung, Bing B; Mesulam, M-Marsel; Siddique, Nailah; Dellefave, Lisa; Caliendo, Janice; Freeman, Stefanie; Siddique, Teepu

    2004-08-01

    Ubiquitinated cytoplasmic inclusions (Ub-CIs) in superficial frontal cortex and dentate gyrus neurons are the hallmark of frontotemporal degeneration of the motor neuron disease-type (FTD-MND-type). To date, 2 reports have described intranuclear ubiquitinated inclusions (Ub-INIs) in 9 cases of familial FTD-MND-type (without clinical or pathologic motor neuron disease, MND). In the current study we found an additional 11 cases with Ub-INIs. We have identified for the first time among these cases 2 with a negative family history and 3 that have concomitant amyotrophic lateral sclerosis (ALS). The results of the present study i) confirm a previous report of significantly lower average brain weight and longer duration in cases with Ub-INIs, ii) reveal significantly greater striatal neuronal loss and gliosis in cases with intranuclear inclusions, and iii) demonstrate that intranuclear inclusions correlate with cytoplasmic inclusions and dystrophic neurites in frontal cortex and striatum but not in dentate gyrus. In addition, the current study confirms that Ub-INIs are found in familial FTD-MND-type, but also extends the presence of Ub-INIs to familial FTD-MND (with concomitant ALS), and probably also to non-familial FTD-MND-type.

  2. Epidemiology of early-onset dementia: a review of the literature

    Science.gov (United States)

    Vieira, Renata Teles; Caixeta, Leonardo; Machado, Sergio; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Carta, Mauro Giovanni

    2013-01-01

    Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it differs from Senile Dementia, and encloses a significant number of cases; nevertheless, it is still poorly understood and underdiagnosed. This study aims to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia, as well as to show the main causes of EOD and their prevalence in population and non-population based studies. The computer-supported search used the following databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were alcohol-associated dementia, Alzheimer’s disease, dementia, Creutzfeldt-jakob disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar degeneration, Huntington’s disease, mixed dementia, neurodegenerative disorders, Parkinson’s disease dementia, presenile dementia, traumatic brain injury, vascular dementia. Only papers published in English and conducted from 1985 up to 2012 were preferentially reviewed. Neurodegenerative diseases are the most common etiologies seen in EOD. Among the general population, the prevalence of EOD was found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years old, with an increasing incidence with age. The progression of EOD was found to range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years. Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of epidemiological studies to elucidate how environmental issues contribute to EOD are necessary, thus, we can collaborate in the planning and prevention of services toward dementia patients. PMID:23878613

  3. Lewy body dementia: the impact on patients and caregivers.

    Science.gov (United States)

    Zweig, Yael R; Galvin, James E

    2014-01-01

    Lewy body dementia (LBD) is the second most common neurodegenerative dementia in older adults, yet there remains a delay in diagnosis that limits healthcare providers' ability to maximize therapeutic outcomes and enhance patient and caregiver quality of life. The impact of LBD on patients includes limiting the potential exposure to medications that may cause adverse outcomes, and addressing how the disease manifestations, such as autonomic features and behavior, affect quality of life. LBD impact on caregivers has been discussed to a greater degree in the literature, and there is clear evidence of caregiver burden and grief associated with disease manifestations. Other common caregiving concerns, such as access to care, prevention of hospitalization, managing behavior, and reviewing prognosis and nursing home placement, are important to comprehensively address the needs of patients with LBD and their caregivers.

  4. The Mental Status Examination in Patients With Suspected Dementia

    Science.gov (United States)

    Grossman, Murray; Irwin, David J.

    2016-01-01

    ABSTRACT Purpose of Review: This article describes a comprehensive approach to the mental status examination and diagnostic workup of patients suspected of having an emerging neurodegenerative dementia. Key strategies for obtaining a history and bedside examination techniques are highlighted. Recent Findings: Classic descriptions of behavioral neurology syndromes were largely based on clinicopathologic correlations of strategic lesions in stroke patients. While still very important, advances in neuroimaging have expanded our armamentarium of cognitive evaluations to include assessments of findings in nonstroke anatomic distributions of disease. These efforts support comprehensive assessments of large-scale cerebral networks in cognitive neurology. Summary: A thorough and focused mental status examination is essential for the evaluation of patients with cognitive symptoms. Selective use of laboratory testing and neuroimaging can aid in the diagnosis of dementia by excluding non-neurodegenerative etiologies. Neurodegenerative disease–specific tests are in development and will enhance diagnosis and efforts for disease-modifying therapy development. PMID:27042900

  5. Inequalities in Access to Treatment and Care for Patients with Dementia and Immigrant Background

    DEFF Research Database (Denmark)

    Stevnsborg, Lea; Jensen-Dahm, Christina; Nielsen, Thomas R

    2016-01-01

    measure for adherence). Non-Western immigrants were significantly less likely to live in a nursing home (0.52 [0.41-0.65]). CONCLUSION: This nationwide registry-based study indicated a worrisome difference in access to anti-dementia treatment and care for dementia patients with an immigrant background......BACKGROUND: Previous studies demonstrated lower quality diagnostic assessment of dementia in immigrant populations, but knowledge about the quality of treatment and care for dementia is still lacking. OBJECTIVE: To conduct a nationwide registry-based study to determine whether inequality exists...... regarding access to anti-dementia treatment and care between immigrant and Danish-born patients with dementia. METHODS: A cross-sectional register-based study was conducted in the entire elderly (60≥years) population with dementia in Denmark in 2012 (n = 34,877). The use of anti-dementia drugs and residency...

  6. Occult CSF flow disturbance of patients with Alzheimer type dementia and vascular dementia; Results from Iotrolan CT-cisternography

    Energy Technology Data Exchange (ETDEWEB)

    Kono, Kazuhiko; Sugita, Yasuko; Funaki, Chiaki (Nagoya Univ. (Japan). Faculty of Medicine) (and others)

    1994-04-01

    We report results of Iotrolan CT-cisternography on 41 demented patients (13 males and 28 females) to find 'occult normal pressure hydrocephalus'. These patients were suspected to have CSF flow disturbance from clinical symptoms and simple brain CT scan findings. Their average age, duration of dementia, and score of Hasegawa's dementia scale (HDS) were 76.2 years, 5.9 years, 9.5/32.5,respectively. Before performing CT-cisternography, clinical diagnosis for their dementia were vascular dementia in 18 patients. Alzheimer type dementia in 12, suspect of NPH in 5, and other diagnoses in 6. From the results of cisternography, we found 13 patients with CSF flow disturbance (contrast material remained in the ventricle more than 48 hours after injection), and 17 patients with normal CSF flow. The former showed lower scores of HDS, higher urinary incontinence scores and smaller areas of the interhemispheric fissure on CT scan than the latter. But the former showed no significant difference from the latter in the average age, duration of dementia and width of the ventricles. (author).

  7. Theory of mind impairments in patients with semantic dementia

    Science.gov (United States)

    Duval, Céline; Bejanin, Alexandre; Piolino, Pascale; Laisney, Mickael; De La Sayette, Vincent; Belliard, Serge; Eustache, Francis; Desgranges, Béatrice

    2012-01-01

    Summary Semantic dementia is characterized by semantic deficits and behavioural abnormalities which occur in the wake of bilateral inferolateral and predominantly left-sided anterior temporal lobe atrophy. The temporal poles have been shown to be involved in theory of mind, namely the ability to ascribe cognitive and affective mental states to others that regulates social interactions by predicting and interpreting human behaviour. However, very few studies have examined theory of mind in semantic dementia. In this study, we investigated both cognitive and affective theory of mind in a group of semantic dementia patients, using separate objective and subjective assessment tasks. Results provided objective evidence of an impact of semantic dementia on cognitive and affective theory of mind, consistent with the patients’ atrophy in the left temporal lobe and hypometabolism in the temporal lobes and the medial frontal cortex. However, the subjective assessment of theory of mind suggested that awareness of the affective but not cognitive theory of mind deficit persists into the moderate stage of the disease. PMID:22232593

  8. Cerebrospinal Fluid Biomarkers in Dementia Patients with Cerebral Amyloid Angiopathy

    Institute of Scientific and Technical Information of China (English)

    Yan-feng Li; Fang-fang Ge; Yong Zhang; Hui You; Zhen-xin Zhang

    2015-01-01

    Objective To study the changes of biomarkers in cerebrospinal fluid (CSF) in cerebral amyloid angiopathy (CAA) dementia and Alzheimer's disease. Methods Levels of amyloid proteinβ (Aβ42, Aβ40) and phosphorylated Tau-protein (P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011. Results The levels of Aβ42, Aβ40, and P-tau in CSF and ratio of Aβ42/Aβ40 were (660.4±265.2) ng/L, (7111.0±1033.4) ng/L, (71.8±51.5) ng/L, and 0.077±0.033, respectively in CAA dementia and (663.6±365.6) ng/L, (5115.0±2931.1) ng/L, (47.7±38.8) ng/L, and 0.192±0.140, respectively in Alzheimer's disease patients. There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers (allP>0.05). Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.

  9. A Quest for Meaning: Hospice Social Workers and Patients with End-Stage Dementia

    Science.gov (United States)

    Sanders, Sara; Swails, Peggy

    2011-01-01

    Research shows that few social workers are interested in working with cognitively impaired older adults, such as those with Alzheimer's disease or a related dementia. As the number of individuals with dementia grows, the demand for social workers to provide services to patients with dementia will increase. Although much attention has been given to…

  10. CSF neurofilament concentration reflects disease severity in frontotemporal degeneration

    Science.gov (United States)

    Scherling, Carole S.; Hall, Tracey; Berisha, Flora; Klepac, Kristen; Karydas, Anna; Coppola, Giovanni; Kramer, Joel H.; Rabinovici, Gil; Ahlijanian, Michael; Miller, Bruce L.; Seeley, William; Grinberg, Lea T.; Rosen, Howard; Meredith, Jere; Boxer, Adam L.

    2014-01-01

    Objective Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders including frontotemporal degeneration (FTD). We investigated the clinical correlates of elevated CSF NfL levels in FTD. Methods CSF NfL, amyloid-β42 (Aβ42), tau and phosphorylated tau (ptau) concentrations were compared in 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) of FTD-causing mutations, 79 FTD (45 behavioral variant frontotemporal dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic dementia [SD]), 22 progressive supranuclear palsy, 50 Alzheimer’s disease, 6 Parkinson’s disease and 17 corticobasal syndrome patients. Correlations between CSF analyte levels were performed with neuropsychological measures and the Clinical Dementia Rating scale sum of boxes (CDRsb). Voxel-based morphometry of structural MR images determined the relationship between brain volume and CSF NfL. Results Mean CSF NfL concentrations were higher in bvFTD, SD and PNFA than other groups. NfL in NC2 was similar to NC. CSF NfL, but not other CSF measures, correlated with CDRsb and neuropsychological measures in FTD, and not in other diagnostic groups. Analyses in two independent FTD cohorts and a group of autopsy verified or biomarker enriched cases confirmed the larger group analysis. In FTD, gray and white matter volume negatively correlated with CSF NfL concentration, such that individuals with highest NfL levels exhibited the most atrophy. Interpretation CSF NfL is elevated in symptomatic FTD and correlates with disease severity. This measurement may be a useful surrogate endpoint of disease severity in FTD clinical trials. Longitudinal studies of CSF NfL in FTD are warranted. PMID:24242746

  11. Apraxias in neurodegenerative dementias

    Directory of Open Access Journals (Sweden)

    Sadanandavalli Retnaswami Chandra

    2015-01-01

    Full Text Available Background: Apraxia is a state of inability to carry out a learned motor act in the absence of motor, sensory or cerebellar defect on command processed through the Praxis circuit. Breakdown in default networking is one of the early dysfunction in cortical dementias and result in perplexity, awkwardness, omission, substitution errors, toying behavior and unrecognizable gestures in response to command with voluntary reflex dissociation where, when unobserved patient will carry out reflex movements normally. Awareness into the organicity of these phenomenas will help in early diagnosis, which will help in initiating appropriate treatment and slowing down the progression of the disease. Aims and Objectives: The aim was to look for the various kinds of apraxias in patients with dementia using appropriate simple tests. Patients and Methods: Three hundred patients satisfying Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for dementia were evaluated in detail with mandatory investigations for dementia followed by testing for ideational, ideomotor, limb-kinetic, buccopharyngeal, dressing apraxia, constructional apraxia and gait apraxias in addition to recording of rare apraxias when present. Results: Alzheimer′s disease showed maximum association with apraxias in all the phases of the disease ideational, ideomotor, dressing and constructional apraxias early and buccopharyngeal and gait apraxia late. Frontotemporal lobe dementia showed buccopharyngeal and gait apraxias late into the disease. Cortical basal ganglionic degeneration showed limb apraxias and diffuse Lewy body disease showed more agnosias and less apraxias common apraxias seen was Ideational and Ideomotor. Conclusion: Recognition of the apraxias help in establishing organicity, categorization, caregiver education, early strategies for treatment, avoiding anti-psychotics and introducing disease modifying pharmacotherapeutic agents and also prognosticating.

  12. A novel progranulin mutation causing frontotemporal lobar degeneration with heterogeneous phenotypic expression.

    Science.gov (United States)

    Rossi, Giacomina; Piccoli, Elena; Benussi, Luisa; Caso, Francesca; Redaelli, Veronica; Magnani, Giuseppe; Binetti, Giuliano; Ghidoni, Roberta; Perani, Daniela; Giaccone, Giorgio; Tagliavini, Fabrizio

    2011-01-01

    Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder characterized by behavioural disturbances and cognitive decline. Here we describe an Italian family with FTLD showing remarkable phenotypic heterogeneity. Based on low plasma levels of progranulin, we analyzed the progranulin gene (GRN) in two patients with early onset and found the novel frame-shift mutation T278SfsX7. mRNA analysis confirmed the null effect of the mutation. The patients were homozygous for H1 MAPT haplotype, a disease modifier factor that can account for early age at onset. Being predictive for GRN null mutations, plasma progranulin dosage should be included in diagnostic work-up of dementia.

  13. EEG Dominant Frequency Peak Differentiates Between Alzheimer's Disease and Frontotemporal Lobar Degeneration.

    Science.gov (United States)

    Goossens, Joery; Laton, Jorne; Van Schependom, Jeroen; Gielen, Jeroen; Struyfs, Hanne; Van Mossevelde, Sara; Van den Bossche, Tobi; Goeman, Johan; De Deyn, Peter Paul; Sieben, Anne; Martin, Jean-Jacques; Van Broeckhoven, Christine; van der Zee, Julie; Engelborghs, Sebastiaan; Nagels, Guy

    2017-01-01

    We investigated the power of EEG as biomarker in differential diagnosis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). EEG was recorded from 106 patients with AD or FTLD, of which 37 had a definite diagnosis, and 40 controls. Dominant frequency peaks were extracted for all 19 channels, for each subject. The average frequency of the largest dominant frequency peaks (maxpeak) was significantly lower in AD than FTLD patients and controls. Based on ROC analysis, classification could be made with diagnostic accuracy of 78.9%. Our findings show that quantitative analysis of EEG maxpeak frequency is an easy and useful measure for differential dementia diagnosis.

  14. Caring for elderly patients with dementia: nursing interventions

    OpenAIRE

    Joosse LL; Palmer D; Lang NM

    2013-01-01

    Laura L Joosse,1 Debra Palmer,1 Norma M Lang21University of Wisconsin-Milwaukee, College of Nursing, Milwaukee, WI, USA; 2University of Wisconsin-Milwaukee, College of Nursing, Knowledge Based Nursing Research Initiative, Milwaukee, WI, USAAbstract: Elderly patients suffering from chronic cognitive decline/dementia are susceptible to poor quality of care which further erodes their quality of life. Seemingly benign events can create cascade iatrogenesis in those whose compensatory ability is c...

  15. First Do No Harm: Euthanasia of Patients with Dementia in Belgium.

    Science.gov (United States)

    Cohen-Almagor, Raphael

    2016-02-01

    In Memory of Ed Pellegrino. Euthanasia in Belgium is not limited to terminally ill patients. It may be applied to patients with chronic degenerative diseases. Currently, people in Belgium wish to make it possible to euthanize incompetent patients who suffer from dementia. This article explains the Belgian law and then explores arguments for and against euthanasia of patients with dementia. It probes the dementia paradox by elucidating Dworkin's distinction between critical and experiential interests, arguing that at the end-of-life this distinction is not clearcut. It argues against euthanasia for patients with dementia, for respecting patients' humanity and for providing them with more care, compassion, and good doctoring.

  16. Processing ambiguity in a linguistic context: decision-making difficulties in non-aphasic patients with behavioral variant frontotemporal degeneration

    Science.gov (United States)

    Spotorno, Nicola; Healey, Meghan; McMillan, Corey T.; Rascovsky, Katya; Irwin, David J.; Clark, Robin; Grossman, Murray

    2015-01-01

    Some extent of ambiguity is ubiquitous in everyday conversations. For example, words have multiple meaning and very common pronouns, like “he” and “she” (anaphoric pronouns), have little meaning on their own and refer to a noun that has been previously introduced in the discourse. Ambiguity triggers a decision process that is not a subroutine of language processing but rather a more general domain resource. Therefore non-aphasic patients with limited decision-making capability can encounter severe limitation in language processing due to extra linguistic limitations. In the present study, we test patients with behavioral variant frontotemporal degeneration (bvFTD), focusing on anaphora as a paradigmatic example of ambiguity resolution in the linguistic domain. bvFTD is characterized by gray matter (GM) atrophy in prefrontal cortex, but relative sparing of peri-Sylvian cortex. A group of patients with parietal disease due to corticobasal syndrome (CBS) was also tested here in order to investigate the specific role of prefrontal cortex in the task employed in the current study. Participants were presented with a pair of sentences in which the first sentence contained two nouns while the second contained a pronoun. In the experimental (ambiguous) condition, both nouns are plausible referents of the pronoun, thus requiring decision-making resources. The results revealed that bvFTD patients are significantly less accurate than healthy seniors in identifying the correct referent of a pronoun in the ambiguous condition, although CBS patients were as accurate as healthy seniors. Imaging analyses related bvFTD patients’ performance to GM atrophy in ventromedial prefrontal cortex (vmPFC). These results suggest that bvFTD patients have difficulties in decision processes that involve the resolution of an ambiguity. PMID:26578928

  17. ACR-ASNR Practice Parameter for Brain PET/CT Imaging Dementia.

    Science.gov (United States)

    Frey, Kirk A; Lodge, Martin A; Meltzer, Carolyn Cidis; Peller, Patrick J; Wong, Terence Z; Hess, Christopher P; Petrella, Jeffrey R; Sair, Haris I; Subramaniam, Rathan M

    2016-02-01

    This practice parameter is for both FDG and amyloid brain PET or PET/computed tomography (CT) for patients with cognitive decline, and has been developed collaboratively by the American College of Radiology (ACR) and the American Society for Neuroradiology (ASNR). It is estimated that the number of people with dementia, 36.5 million worldwide in 2010, will increase to 65.7 million in 2030 and to 115 million in 2050. Four primary neurodegenerative etiologies of dementia have been defined: Alzheimer disease (AD), vascular dementia, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Alzheimer disease is the most common form of dementia, accounting for approximately 60%-80% of all cases. Indications for FDG and amyloid brain PET and qualifications for personnel are discussed in this practice parameter.

  18. Degenerative dementia: nosological aspects and results of single photon emission computed tomography; Les demences degeneratives: aspects nosologiques et resultats de la tomographie d'emission monophotonique

    Energy Technology Data Exchange (ETDEWEB)

    Dubois, B.; Habert, M.O. [Hopital Pitie-Salpetriere, 75 - Paris (France)

    1999-12-01

    Ten years ago, the diagnosis discussion of a dementia case for the old patient was limited to two pathologies: the Alzheimer illness and the Pick illness. During these last years, the frame of these primary degenerative dementia has fallen into pieces. The different diseases and the results got with single photon emission computed tomography are discussed. for example: fronto-temporal dementia, primary progressive aphasia, progressive apraxia, visio-spatial dysfunction, dementia at Lewy's bodies, or cortico-basal degeneration. (N.C.)

  19. Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration

    Directory of Open Access Journals (Sweden)

    Jennifer M. Harris

    2016-06-01

    Full Text Available Background/Objectives: We aimed to evaluate the co-occurrence of language and behavioural impairment in patients with frontotemporal lobar degeneration (FTLD spectrum pathology. Methods: Eighty-one dementia patients with pathological confirmation of FTLD were identified. Anonymized clinical records from patients' first assessment were rated for language and behavioural features from frontotemporal dementia consensus criteria, primary progressive aphasia (PPA criteria and 1998 FTLD criteria. Results: Over 90% of patients with FTLD pathology exhibited a combination of at least one behavioural and one language feature. Changes in language, in particular, were commonly accompanied by behavioural change. Notably, the majority of patients who displayed language features characteristic of semantic variant PPA exhibited ‘early perseverative, stereotyped or compulsive/ritualistic behaviour'. Moreover, ‘executive/generation deficits with relative sparing of memory and visuospatial functions' occurred in most patients with core features of non-fluent variant PPA. Conclusion: Behavioural and language symptoms frequently co-occur in patients with FTLD pathology. Current classifications, which separate behavioural and language syndromes, do not reflect this co-occurrence.

  20. The Rapid Assessment Interface and Discharge service and its implications for patients with dementia

    OpenAIRE

    Singh I; Ramakrishna S; Williamson K

    2013-01-01

    Inderpal Singh,1 Sharan Ramakrishna,1 Kathryn Williamson21Department of Geriatric Medicine, 2Department of Old Age Psychiatry, Ysbyty Ystrad Fawr, Ystrad Mynach, Caerphilly, United KingdomAbstract: The rising prevalence of dementia will have an effect on acute care hospitals around the world. At present, around 40% of patients older than 70 years with acute medical admissions have dementia, but only half of these patients have been diagnosed. Patients with dementia have poorer health outcomes...

  1. Dural Reduction Surgery: A Treatment Option for Frontotemporal Brain Sagging Syndrome.

    Science.gov (United States)

    Mostofi, Emily; Schievink, Wouter I; Sim, Valerie L

    2016-07-01

    Frontotemporal brain sagging syndrome is a dementia associated with hypersomnolence, personality changes, and features of intracranial hypotension on magnetic resonance imaging. The literature is sparse with respect to treatment options; many patients simply worsen. We present a case in which this syndrome responded to lumbar dural reduction surgery. Postoperative magnetic resonance imaging indicated normalization of brain sagging and lumbar intrathecal pressure. Although no evidence of cerebrospinal leak was found, extremely thin dura was noted intraoperatively, suggesting that a thin and incompetent dura could result in this low-pressure syndrome. Clinicians who encounter this syndrome should consider dural reduction surgery as a treatment strategy.

  2. FDG PET imaging dementia

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol [Kyungpook National University Medical School and Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2007-04-15

    Dementia is a major burden for many countries including South Korea, where life expectancy is continuously growing and the proportion of aged people is rapidly growing. Neurodegenerative disorders, such as, Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia. Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, Huntington disease, can cause dementia, and cerebrovascular disease also can cause dementia. Depression or hypothyroidism also can cause cognitive deficits, but they are reversible by management of underlying cause unlike the forementioned dementias. Therefore these are called pseudodementia. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new drugs postpone progression of dementias or target specific proteins that cause dementia. Efficient pharmacologic treatment of dementia needs not only to distinguish underlying causes of dementia but also to be installed as soon as possible. Therefore, differential diagnosis and early diagnosis of dementia are utmost importance. F-18 FDG PET is useful for clarifying dementing diseases and is also useful for early detection of the disease. Purpose of this article is to review the current value of FDG PET for dementing diseases including differential diagnosis of dementia and prediction of evolving dementia.

  3. MR spectroscopy in dementia; MR-Spektroskopie bei Demenz

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, T.; Gerigk, L.; Giesel, F.; Schuster, L.; Essig, M. [Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Abteilung E010, Radiologie, Heidelberg (Germany)

    2010-09-15

    With an increasingly aging population we are faced with the problem of an increasing number of dementia patients. In addition to clinical, neuropsychological and laboratory procedures, MRI plays an important role in the early diagnosis of dementia. In addition to various morphological changes functional changes can also help in the diagnosis and differential diagnosis of dementia. Overall the diagnosis of dementia can be improved by using parameters from MR spectroscopy. This article focuses on MR spectroscopic changes in the physiological aging process as well as on changes in mild cognitive impairment a precursor of Alzheimer's dementia, in Alzheimer's dementia, frontotemporal dementia, vascular dementia and Lewy body dementia. (orig.) [German] Angesichts einer immer aelter werdenden Bevoelkerung sind wir mit dem Problem einer zunehmenden Zahl an Demenzerkrankungen konfrontiert. Neben klinischen, neuropsychologischen und laborchemischen Verfahren spielt die MRT zur Fruehdiagnostik einer Demenz eine wichtige Rolle. Morphologische Veraenderungen wie auch verschiedene funktionelle Verfahren helfen bei der Diagnostik und Differenzialdiagnostik einer Demenz. Insgesamt kann mittels MR-spektroskopischer Parameter die Diagnostik einer Demenz verbessert werden. In diesem Artikel soll auf MR-spektroskopische Veraenderungen im Rahmen des physiologischen Alterungsprozesses eingegangen werden. Ferner werden speziell Veraenderungen bei leichter kognitiver Beeintraechtigung, einer Vorform der Alzheimer-Demenz, bei Alzheimer-, frontotemporaler, vaskulaerer und Lewy-Koerper-Demenz eroertert. (orig.)

  4. Dissecting molecular mechanisms in the living brain of dementia patients.

    Science.gov (United States)

    Barrio, Jorge R; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Petric, Andrej; Small, Gary W; Kepe, Vladimir

    2009-07-21

    Understanding the molecular mechanisms associated with the development of dementia is essential for designing successful interventions. Dementia, like cancer and cardiovascular disease, requires early detection to potentially arrest or prevent further disease progression. By the time a neurologist begins to manage clinical symptoms, the disease has often damaged the brain significantly. Because successful treatment is the logical goal, detecting the disease when brain damage is still limited is of the essence. The role of chemistry in this discovery process is critical. With the advent of molecular imaging, the understanding of molecular mechanisms in human neurodegenerative diseases has exploded. Traditionally, knowledge of enzyme and neurotransmitter function in humans has been extrapolated from animal studies, but now we can acquire data directly from both healthy and diseased human subjects. In this Account, we describe the use of molecular imaging probes to elucidate the biochemical and cellular bases of dementia (e.g., Alzheimer's disease) and the application of these discoveries to the design of successful therapeutic interventions. Molecular imaging permits observation and evaluation of the basic molecular mechanisms of disease progression in the living brains of patients. 2-Deoxy-2-[(18)F]fluoro-d-glucose is used to assess the effect of Alzheimer's disease progression on neuronal circuits projecting from and to the temporal lobe (one of the earliest metabolic signs of the disease). Recently, we have developed imaging probes for detection of amyloid neuropathology (both tau and beta-amyloid peptide deposits) and neuronal losses. These probes allow us to visualize the development of pathology in the living brain of dementia patients and its consequences, such as losses of critical neurons associated with memory deficits and other neuropsychiatric impairments. Because inflammatory processes are tightly connected to the brain degenerative processes

  5. Patient Preferences May Be Indicative of Normative Issues in Dementia Research.

    Science.gov (United States)

    Forlini, Cynthia

    2017-01-01

    Robillard and Feng highlight incongruence between patient preferences and the procedural aspects of research ethics as they relate to protocols for dementia research. Their findings break ground for a reassessment of how research ethics, researchers, and participants (including patients and caregivers) approach participation in dementia research. However, it is unclear whether patient preferences may also herald a normative gap between how dementia research is being conducted and how it should be done. This response uses one of Robillard and Feng's findings to illustrate how descriptive empirical data might be reinterpreted into normative questions that reframe current practices in the context of dementia research.

  6. Multimodal FMRI resting-state functional connectivity in granulin mutations: the case of fronto-parietal dementia.

    Directory of Open Access Journals (Sweden)

    Enrico Premi

    Full Text Available BACKGROUND: Monogenic dementias represent a great opportunity to trace disease progression from preclinical to symptomatic stages. Frontotemporal Dementia related to Granulin (GRN mutations presents a specific framework of brain damage, involving fronto-temporal regions and long inter-hemispheric white matter bundles. Multimodal resting-state functional MRI (rs-fMRI is a promising tool to carefully describe disease signature from the earliest disease phase. OBJECTIVE: To define local connectivity alterations in GRN related pathology moving from the presymptomatic (asymptomatic GRN mutation carriers to the clinical phase of the disease (GRN- related Frontotemporal Dementia. METHODS: Thirty-one GRN Thr272fs mutation carriers (14 patients with Frontotemporal Dementia and 17 asymptomatic carriers and 38 healthy controls were recruited. Local connectivity measures (Regional Homogeneity (ReHo, Fractional Amplitude of Low Frequency Fluctuation (fALFF and Degree Centrality (DC were computed, considering age and gender as nuisance variables as well as the influence of voxel-level gray matter atrophy. RESULTS: Asymptomatic GRN carriers had selective reduced ReHo in the left parietal region and increased ReHo in frontal regions compared to healthy controls. Considering Frontotemporal Dementia patients, all measures (ReHo, fALFF and DC were reduced in inferior parietal, frontal lobes and posterior cingulate cortex. Considering GRN mutation carriers, an inverse correlation with age in the posterior cingulate cortex, inferior parietal lobule and orbitofrontal cortex was found. CONCLUSIONS: GRN pathology is characterized by functional brain network alterations even decades before the clinical onset; they involve the parietal region primarily and then spread to the anterior regions of the brain, supporting the concept of molecular nexopathies.

  7. Qualitative aspects of learning, recall, and recognition in dementia

    Directory of Open Access Journals (Sweden)

    Ranjith Neelima

    2010-01-01

    Full Text Available Objective: To determine whether learning and serial position effect (SPE differs qualitatively and quantitatively among different types of dementia and between dementia patients and controls; we also wished to find out whether interference affects it. Materials and Methods: We administered the Malayalam version of the Rey Auditory Verbal Learning Test (RAVLT to 30 cognitively unimpaired controls and 80 dementia patients [30 with Alzheimer′s disease (AD, 30 with vascular dementia (VaD, and 20 with frontotemporal dementia (FTD] with mild severity on the Clinical Dementia Rating Scale. Results: All groups were comparable on education and age, except the FTD group, who were younger. Qualitatively, the learning pattern and SPE (with primacy and recency being superior to intermediate was retained in the AD, VaD, and control groups. On SPE in free recall, recency was superior to intermediate in the FTD group (P < 0.01 using Bonferroni correction. On recognition, the AD and VaD groups had more misses (P < 0.01, while the FTD group had more false positives (P < 0.01. Conclusion: Quantitative learning is affected by dementia. The pattern of qualitative learning remains unaltered in dementia in the early stages.

  8. Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study.

    Science.gov (United States)

    Liu, Ju-Chi; Hsu, Yi-Ping; Kao, Pai-Feng; Hao, Wen-Rui; Liu, Shing-Hwa; Lin, Chao-Feng; Sung, Li-Chin; Wu, Szu-Yuan

    2016-03-01

    Taiwan has the highest prevalence of chronic kidney disease (CKD) worldwide. CKD, a manifestation of vascular diseases, is associated with a high risk of dementia. Here, we estimated the association between influenza vaccination and dementia risk in patients with CKD. Data from the National Health Insurance Research Database of Taiwan were used in this study. The study cohort included all patients diagnosed with CKD (according to International Classification of Disease, Ninth Revision, Clinical Modification codes) at healthcare facilities in Taiwan (n = 32,844) from January 1, 2000, to December 31, 2007. Each patient was followed up to assess dementia risk or protective factors: demographic characteristics of age and sex; comorbidities of diabetes, hypertension, dyslipidemia, cerebrovascular diseases, parkinsonism, epilepsy, substance and alcohol use disorders, mood disorder, anxiety disorder, psychotic disorder, and sleep disorder; urbanization level; monthly income; and statin, metformin, aspirin, and angiotensin-converting enzyme inhibitor (ACEI) use. A propensity score was derived using a logistic regression model for estimating the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) of dementia among vaccinated and unvaccinated CKD patients. The study population comprised 11,943 eligible patients with CKD; 5745 (48%) received influenza vaccination and the remaining 6198 (52%) did not. The adjusted HRs (aHRs) of dementia decreased in vaccinated patients compared with those in unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.68, 0.58, and 0.64; P dementia in various models. A stronger protective effect against dementia risk was demonstrated during the noninfluenza season. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor and

  9. Pain in dementia: prevalence and associated factors: protocol of a multidisciplinary study

    NARCIS (Netherlands)

    J. van Kooten; S. Delwel; T.T. Binnekade; M. Smalbrugge; J.C. van der Wouden; R.S.G.M. Perez; D. Rhebergen; W.W.A. Zuurmond; M.L. Stek; F. Lobbezoo; C.M.P.M. Hertogh; E.J.A. Scherder

    2015-01-01

    Background Pain is a common problem in people with dementia, however the exact prevalence of pain in dementia subtypes, e.g. Alzheimer’s Disease (AD), Vascular Dementia (VaD), Frontotemporal Dementia (FTD) and dementia with Lewy Bodies (DLB), is unknown, as is the relation between pain and the diffe

  10. Neuropsychiatric symptoms in patients with dementia in primary care: a study protocol

    NARCIS (Netherlands)

    Borsje, P.; Wetzels, R.B.; Lucassen, P.L.B.J.; Pot, A.M.; Koopmans, R.T.C.M.

    2014-01-01

    BACKGROUND: Neuropsychiatric symptoms (NPS) frequently occur in patients with dementia. To date, prospective studies on the course of NPS have been conducted in patients with dementia in clinical centers or psychiatric services. The primary goal of this study is to investigate the course of NPS in p

  11. Prevalence of neuropsychiatric symptoms in a large sample of Dutch nursing home patients with dementia

    NARCIS (Netherlands)

    Zuidema, Sytse U; Derksen, Els; Verhey, Frans R J; Koopmans, Raymond T C M

    2007-01-01

    OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms of dementia patients in Dutch nursing homes. METHODS: Cross-sectional study in a large sample of 1322 demented patients living in 59 dementia special care units (SCUs) in The Netherlands. Symptoms were observed by licensed vocational

  12. Effectiveness of nonpharmacological interventions in delaying the institutionalization of patients with dementia: a meta-analysis.

    NARCIS (Netherlands)

    Spijker, A.; Vernooy-Dassen, M.J.F.J.; Vasse, E.; Adang, E.; Wollersheim, H.; Grol, R.P.T.M.; Verhey, F.

    2008-01-01

    Contemporary healthcare policies are designed to shape the conditions that can help delay the institutionalization of patients with dementia. This can be done by developing support programs that minimize healthcare risks for the patients with dementia and their informal caregivers. Many support prog

  13. Evaluation of Underlying Causes of Death in Patients with Dementia to Support Targeted Advance Care Planning

    NARCIS (Netherlands)

    Van De Vorst, Irene E.; Koek, Huiberdina L.; Bots, Michiel L.; Vaartjes, Ilonca

    2016-01-01

    Background: Insight in causes of death in demented patients may help physicians in end-of-life care. Objectives: To investigate underlying causes of death (UCD) in demented patients stratified by age, sex, dementia subtype [Alzheimer's disease (AD), vascular dementia (VaD)] and to compare them with

  14. Predictors of change and continuity in home care for dementia patients

    NARCIS (Netherlands)

    Vernooy-Dassen, M.J.F.J.; Felling, A.J.A.; Persoon, J.M.G.

    1997-01-01

    Objective. To investigate predictors of change in the sense of competence of primary caregivers and continuity in home care for dementia patients. Design. A prospective longitudinal study with a follow-up period of 10 months. Setting. Dementia patients living in the community selected by Dutch gener

  15. Quality of dementia diagnostic evaluation for ethnic minority patients: a nationwide study

    DEFF Research Database (Denmark)

    Nielsen, T Rune; Andersen, Birgitte Bo; Kastrup, Marianne

    2011-01-01

    Background/Aims: Diagnostic evaluation of dementia for ethnic minority patients may be challenging. This study aimed to evaluate the quality of diagnostic evaluation of dementia for patients from ethnic minorities in Denmark. Methods: The Danish national hospital registers were used to identify p...

  16. The executive interview as a screening test for executive dysfunction in patients with mild dementia

    DEFF Research Database (Denmark)

    Stokholm, Jette; Vogel, Asmus; Gade, Anders;

    2005-01-01

    To validate the Executive Interview (EXIT25) as a screening instrument for executive cognitive dysfunction in patients with mild dementia.......To validate the Executive Interview (EXIT25) as a screening instrument for executive cognitive dysfunction in patients with mild dementia....

  17. The structural neuroanatomy of music emotion recognition: evidence from frontotemporal lobar degeneration.

    Science.gov (United States)

    Omar, Rohani; Henley, Susie M D; Bartlett, Jonathan W; Hailstone, Julia C; Gordon, Elizabeth; Sauter, Disa A; Frost, Chris; Scott, Sophie K; Warren, Jason D

    2011-06-01

    Despite growing clinical and neurobiological interest in the brain mechanisms that process emotion in music, these mechanisms remain incompletely understood. Patients with frontotemporal lobar degeneration (FTLD) frequently exhibit clinical syndromes that illustrate the effects of breakdown in emotional and social functioning. Here we investigated the neuroanatomical substrate for recognition of musical emotion in a cohort of 26 patients with FTLD (16 with behavioural variant frontotemporal dementia, bvFTD, 10 with semantic dementia, SemD) using voxel-based morphometry. On neuropsychological evaluation, patients with FTLD showed deficient recognition of canonical emotions (happiness, sadness, anger and fear) from music as well as faces and voices compared with healthy control subjects. Impaired recognition of emotions from music was specifically associated with grey matter loss in a distributed cerebral network including insula, orbitofrontal cortex, anterior cingulate and medial prefrontal cortex, anterior temporal and more posterior temporal and parietal cortices, amygdala and the subcortical mesolimbic system. This network constitutes an essential brain substrate for recognition of musical emotion that overlaps with brain regions previously implicated in coding emotional value, behavioural context, conceptual knowledge and theory of mind. Musical emotion recognition may probe the interface of these processes, delineating a profile of brain damage that is essential for the abstraction of complex social emotions.

  18. Caring for elderly patients with dementia: nursing interventions

    Directory of Open Access Journals (Sweden)

    Joosse LL

    2013-08-01

    Full Text Available Laura L Joosse,1 Debra Palmer,1 Norma M Lang21University of Wisconsin-Milwaukee, College of Nursing, Milwaukee, WI, USA; 2University of Wisconsin-Milwaukee, College of Nursing, Knowledge Based Nursing Research Initiative, Milwaukee, WI, USAAbstract: Elderly patients suffering from chronic cognitive decline/dementia are susceptible to poor quality of care which further erodes their quality of life. Seemingly benign events can create cascade iatrogenesis in those whose compensatory ability is compromised by impairments in multiple domains. Under recognition, misrecognition, or failure to intervene and manage this vulnerable population leads to suboptimal care. This places them at risk for cognitive decline, functional decline, and challenging behaviors, creating financial and emotional burdens for not only the patients but also family, staff, and organizations that are attempting to provide care. Identifying, managing, and therapeutically responding to confused elderly is complex. Recognizing the challenges makes the development of tools that guide comprehensive assessment planning, interpretation of findings, and treatment plans imperative. Innovative and effective assessment and interventional approaches are present in the literature. This article synthesizes the scientific evidence to guide clinicians to implement in practice.Keywords: dementia, older adults, assessment, intervention, quality of life, elderly, cognitive decline

  19. Increased risk of hip fractures in patients with dementia: a nationwide population-based study

    OpenAIRE

    Wang, Hao-Kuang; Hung, Chao-Ming; Lin, Sheng-Hsiang; Tai, Yi-Cheng; Lu, Kang; Liliang, Po-Chou; Lin, Chi-Wei; Lee, Yi-Che; Fang, Pei-Hsuan; Chang, Li-Ching; Li, Ying-Chun

    2014-01-01

    Background Dementia has been associated with an increased risk of hip fracture. However, little research has been conducted on the impact of dementia on wrist or vertebral fracture development. The aim of this study was to investigate whether dementia is a risk factor for different types of fracture in Taiwan. Methods The study sample was drawn from Taiwan’s National Health Insurance Research Database of reimbursement claims, and comprised 1408 patients who visited ambulatory care centers or ...

  20. Efficacy of communication among nurses and elderly patients suffering from the dementia of Alzheimer type

    OpenAIRE

    Ahmad, Muhammad Nasir

    2014-01-01

    Dementia is a syndrome. It consists of multiple cognitive deficits sufficient to interfere with social and occupational functioning. The most common cause of dementia is Alzheimer disease. Patients with dementia have trouble with intentional communication because by definition, they have multiple cognitive deficits. They have difficulty producing linguistic information because they have trouble in thinking, generating, and ordering ideas. They have difficulty in comprehending language because...

  1. Caregivers' understanding of dementia predicts patients' comfort at death: a prospective observational study.

    Science.gov (United States)

    van der Steen, Jenny T; Onwuteaka-Philipsen, Bregje D; Knol, Dirk L; Ribbe, Miel W; Deliens, Luc

    2013-04-11

    Patients with dementia frequently do not receive adequate palliative care which may relate to poor understanding of the natural course of dementia. We hypothesized that understanding that dementia is a progressive and terminal disease is fundamental to a focus on comfort in dementia, and examined how family and professional caregivers' understanding of the nature of the disease was associated with patients' comfort during the dying process. We enrolled 372 nursing home patients from 28 facilities in The Netherlands in a prospective observational study (2007 to 2010). We studied both the families and the physicians (73) of 161 patients. Understanding referred to families' comprehension of complications, prognosis, having been counseled on these, and perception of dementia as "a disease you can die from" (5-point agreement scale) at baseline. Physicians reported on this perception, prognosis and having counseled on this. Staff-assessed comfort with the End-of-Life in Dementia - Comfort Assessment in Dying (EOLD-CAD) scale. Associations between understanding and comfort were assessed with generalized estimating equations, structural equation modeling, and mediator analyses. A family's perception of dementia as "a disease you can die from" predicted higher patient comfort during the dying process (adjusted coefficient -0.8, 95% confidence interval (CI): -1.5; -0.06 point increment disagreement). Family and physician combined perceptions (-0.9, CI: -1.5; -0.2; 9-point scale) were also predictive, including in less advanced dementia. Forty-three percent of the families perceived dementia as a disease you can die from (agreed completely, partly); 94% of physicians did. The association between combined perception and higher comfort was mediated by the families' reporting of a good relationship with the patient and physicians' perception that good care was provided in the last week. Awareness of the terminal nature of dementia may improve patient comfort at the end of life

  2. Tau Rather than TDP-43 Proteins are Potential Cerebrospinal Fluid Biomarkers for Frontotemporal Lobar Degeneration Subtypes: A Pilot Study

    NARCIS (Netherlands)

    Kuiperij, H.B.; Versleijen, A.A.; Beenes, M.; Verwey, N.A.; Benussi, L.; Paterlini, A.; Binetti, G.; Teunissen, C.E.; Raaphorst, J.; Schelhaas, H.J.; Kusters, B.; Pijnenburg, Y.A.; Ghidoni, R.; Verbeek, M.M.

    2016-01-01

    BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous disease both at the clinical, genetic, and pathobiological level. The underlying pathological spectrum (termed FTLD, frontotemporal lobar degeneration) is in most cases defined by accumulation of either tau (FTLD-tau) or TDP-43 proteins

  3. RISK OF DEMENTIA IN PERITONEAL DIALYSIS PATIENTS COMPARED WITH HEMODIALYSIS PATIENTS

    Science.gov (United States)

    Wolfgram, Dawn F.; Szabo, Aniko; Murray, Anne M.; Whittle, Jeff

    2016-01-01

    Background Compared with similarly aged controls, patients with end-stage renal disease (ESRD) have a higher prevalence of cognitive impairment and more rapid cognitive decline, which is not explained by traditional risk factors alone. Since previous small studies suggest an association of cognitive impairment with dialysis modality, we compared incident dementia among patients initiating hemodialysis (HD) versus peritoneal dialysis (PD) in a large national cohort. Methods This is a retrospective cohort study of incident dialysis patients in the United States from 2006 to 2008 with no diagnosis of dementia prior to beginning dialysis. We evaluated the effect of initial dialysis modality on incidence of dementia, diagnosed by Medicare claims data, adjusted for baseline demographic and clinical data from USRDS registry. Results Our analysis included 121,623 patients, of whom 8,663 initiated dialysis on PD. The mean age of our cohort was 69.2 years. Patients who initiated on PD had a lower cumulative incidence of dementia than those who initiated HD (1.0% versus 2.7%, 2.5% versus 5.3%, and 3.9% versus 7.3% at 1, 2, and 3 years, respectively). The risk of dementia for patients who started on PD was lower compared with those who started on HD, with a hazard ratio (HR) = 0.46 [0.41, 0.53], in an unadjusted model and HR 0.74 [0.64, 0.86] in a matched model. Conclusions Dialysis modality is associated with incident dementia in a cohort of older ESRD patients. This finding warrants further investigation of the effect of dialysis modality on cognitive function and evaluation for possible mechanisms. PMID:25742686

  4. Personality changes in dementia: are they disease specific and universal?

    Science.gov (United States)

    Torrente, Fernando; Pose, Mariángeles; Gleichgerrcht, Ezequiel; Torralva, Teresa; López, Pablo; Cetkovich-Bakmas, Marcelo; Manes, Facundo

    2014-01-01

    Previous studies about personality changes in dementia suggest that they may be due to the disruption of the biological basis of personality traits, and hence, that they are disease specific and universal. However, evidence about its specificity is still limited and scarce regarding culturally diverse populations. Accordingly, our aim was to compare personality changes in Argentinean patients with Alzheimer disease, behavioral variant of frontotemporal dementia, and primary progressive aphasia. The closest living relatives of patients diagnosed with Alzheimer disease (n=19), behavioral variant of frontotemporal dementia (n=16), and primary progressive aphasia (n=15) were asked to complete 2 versions of the personality inventory NEO Personality Inventory-Revised, one for assessing patients' premorbid personality traits, and the other for assessing current traits. All groups showed changes in several domains and facets of the NEO Personality Inventory-Revised. Globally, the observed pattern of changes was fairly consistent with previous studies based on the same model of personality. Nevertheless, our results regarding disease-specificity were less conclusive. Even if there were some indicators of specific differences between groups, most traits varied similarly across the 3 groups, revealing a pattern of generalized changes in personality expression after illness onset. More studies are needed that help to distinguish real personality changes from other affective or cognitive symptoms that accompany dementia, as well as further data from culturally diverse populations.

  5. Semantic dementia: Brazilian study of nineteen cases

    Directory of Open Access Journals (Sweden)

    Mirna Lie Hosogi Senaha

    Full Text Available Abstract The term semantic dementia was devised by Snowden et al. in 1989 and nowadays, the semantic dementia syndrome is recognized as one of the clinical forms of frontotemporal lobar degeneration (FTLD and is characterized by a language semantic disturbance associated to non-verbal semantic memory impairment. Objectives: The aim of this study was to describe a Brazilian sample of 19 semantic dementia cases, emphasizing the clinical characteristics important for differential diagnosis of this syndrome. Methods: Nineteen cases with semantic dementia were evaluated between 1999 and 2007. All patients were submitted to neurological evaluation, neuroimaging exams and cognitive, language and semantic memory evaluation. Results: All patients presented fluent spontaneous speech, preservation of syntactic and phonological aspects of the language, word-finding difficulty, semantic paraphasias, word comprehension impairment, low performance in visual confrontation naming tasks, impairment on tests of non-verbal semantic memory and preservation of autobiographical memory and visuospatial skills. Regarding radiological investigations, temporal lobe atrophy and/or hypoperfusion were found in all patients. Conclusions: The cognitive, linguistic and of neuroimaging data in our case series corroborate other studies showing that semantic dementia constitutes a syndrome with well defined clinical characteristics associated to temporal lobe atrophy.

  6. Apathy and depressive mood in nursing home patients with early-onset dementia.

    Science.gov (United States)

    Leontjevas, Ruslan; van Hooren, Susan; Waterink, Wim; Mulders, Ans

    2009-01-01

    The study explored whether apathy and depressive mood symptoms (DMS) are related to cognitive and functional features of dementia in 63 nursing home (NH) residents with early-onset dementia (EOD). All EOD residents from one NH (n = 41) and a random sample from another NH were assessed for depressive symptoms (Montgomery Asberg Depression Rating Scale [MADRS]), apathy (Neuropsychiatric Inventory [NPI]), global cognitive functions (Mini-Mental State Examination [MMSE]), activities of daily living (ADL, Minimum Data Set-Resident Assessment Instrument [MDS-RAI]), and overall dementia severity (Global Deterioration Scale [GDS]). DMS were not associated with apathy and dementia severity. Regression analyses adjusted for age, gender, the type of dementia, and DMS revealed that dementia severity measures accounted, respectively, for 14% (ADL), 13% (GDS), and 9% (MMSE) of the variance in apathy. In line with previous research in older patients, the higher apathy scores were associated with more cognitive and functional problems in EOD.

  7. Issues experienced while administering care to patients with dementia in acute care hospitals: A study based on focus group interviews

    OpenAIRE

    Risa Fukuda; Yasuko Shimizu; Natsuko Seto

    2015-01-01

    Objective: Dementia is a major public health problem. More and more patients with dementia are being admitted to acute care hospitals for treatment of comorbidities. Issues associated with care of patients with dementia in acute care hospitals have not been adequately clarified. This study aimed to explore the challenges nurses face in providing care to patients with dementia in acute care hospitals in Japan. Methods: This was a qualitative study using focus group interviews (FGIs). The setti...

  8. Examining the Association between Vitamin B12 Deficiency and Dementia in High-Risk Hospitalized Patients.

    Science.gov (United States)

    Siswanto, O; Smeall, K; Watson, T; Donnelly-Vanderloo, M; O'Connor, C; Foley, N; Madill, J

    2015-12-01

    To explore the association between vitamin B12 deficiency and dementia in patients at high risk for vitamin B12 deficiency. Chart review. Emergency, critical care/ trauma, neurology, medicine, and rehabilitation units of two hospitals in Southwestern Ontario, Canada. Adult patients (n = 666) admitted from 2010 to 2012. Data collection included: reason for admission, gender, age, clinical signs and symptoms of B12 deficiency, serum B12 concentration, and B12 supplementation. Patients with dementia were identified based on their medication profile and medical history. Vitamin B12 deficiency (pmol/L) was defined as serum B12 concentration 220. Comparisons between B12-deficient patients with and without dementia were examined using parametric and non-parametric tests. Serum B12 values were available for 60% (399/666) of the patients, of whom 4% (16/399) were B12-deficient and 14% (57/399) were marginally deficient. Patients with dementia were not more likely to be B12-deficient or marginally deficient [21% (26/121)] compared to those with no dementia [17% (47/278), p=0.27)]. Based on documentation, 34% (25/73) of the B12-deficient and marginally-deficient patients did not receive B12 supplementation, of whom 40% (10/25) had dementia. In this sample of patients, there was no association between B12 deficiency and dementia. However, appropriate B12 screening protocols are necessary for high risk patient to identify deficiency and then receive B12 supplementation as needed.

  9. The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Chen-Yi Wu

    Full Text Available Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study.To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study.12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD and degenerative dementia. Mortality incidence and hazard ratios (HRs were calculated.The median survival time was 3.39 years (95% confidence interval [CI]: 2.88-3.79 for VaD without medication, 6.62 years (95% CI: 6.24-7.21 for VaD with nootropics, 3.01 years (95% CI: 2.85-3.21 for degenerative dementia without medication, 8.11 years (95% CI: 6.30-8.55 for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73-6.17 for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02-9.87 for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55-2.83 without medication, 1.46 (95% CI: 1.39-1.54 with nootropics, 1.05 (95% CI: 0.82-1.34 with anti-dementia medication, and 0.92 (95% CI: 0.80-1.05 with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15-1.37 than VaD without medication (HR: 2.46, 95% CI: 2.22-2.72.Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.

  10. The Rapid Assessment Interface and Discharge service and its implications for patients with dementia

    Directory of Open Access Journals (Sweden)

    Singh I

    2013-08-01

    Full Text Available Inderpal Singh,1 Sharan Ramakrishna,1 Kathryn Williamson21Department of Geriatric Medicine, 2Department of Old Age Psychiatry, Ysbyty Ystrad Fawr, Ystrad Mynach, Caerphilly, United KingdomAbstract: The rising prevalence of dementia will have an effect on acute care hospitals around the world. At present, around 40% of patients older than 70 years with acute medical admissions have dementia, but only half of these patients have been diagnosed. Patients with dementia have poorer health outcomes, longer hospital stays, and higher rates of readmissions and institutionalization. Worldwide, health care budgets are severely constrained. National Institute for Health and Care Excellence (NICE has listed ten quality standards for supporting people in living well with dementia. NICE resource implications and commissioning support to implement these guidelines and improve dementia services have been recently published. Although most of the frail elderly patients with dementia are cared for by geriatricians, obstacles to making a diagnosis and to the management of dementia have been recognized. To provide a timely diagnosis of dementia, better care in acute hospital settings, and continuity of care in the community, services integrating all these elements are warranted. Extra resources also will be required for intermediate, palliative care, and mental health liaison services for people with dementia. The Birmingham Rapid Assessment Interface and Discharge service model uses a multiskilled team that provides comprehensive assessment of a person's physical and psychological well-being in a general hospital setting. It has been shown to be an effective model in terms of reducing both length of stay and avoiding readmission. The aim of this review is to discuss the implications of the Rapid Assessment Interface and Discharge model in people with dementia and to critically compare this model with similar published service provisions.Keywords: comorbidity, aged

  11. The impact of autonomic dysfunction on survival in patients with dementia with Lewy bodies and Parkinson's disease with dementia.

    Directory of Open Access Journals (Sweden)

    Kajsa Stubendorff

    Full Text Available INTRODUCTION: Autonomic dysfunction is a well-known feature in neurodegenerative dementias, especially common in α-synucleinopathies like dementia with Lewy bodies and Parkinson's disease with dementia. The most common symptoms are orthostatic hypotension, incontinence and constipation, but its relevance in clinical practice is poorly understood. There are no earlier studies addressing the influence of autonomic dysfunction on clinical course and survival. The aim of this study was to investigate the frequency of the three most common features of autonomic dysfunction and analyze how it affects survival. METHODS: Thirty patients with dementia with Lewy bodies and Parkinson's disease with dementia were included in this prospective, longitudinal follow-up study. Presence of incontinence and constipation was recorded at baseline. Blood pressure was measured at baseline, after 3 months and after 6 months according to standardized procedures, with 5 measurements during 10 minutes after rising. Orthostatic hypotension was defined using consensus definitions and persistent orthostatic hypotension was defined as 5 or more measurements with orthostatic hypotension. Difference in survival was analyzed 36 months after baseline. RESULTS: There was a high frequency of persistent orthostatic blood pressure (50%, constipation (30% and incontinence (30%. Patients with persistent orthostatic hypotension had a significantly shorter survival compared to those with no or non-persistent orthostatic hypotension (Log rank x(2 = 4.47, p = 0.034. Patients with constipation and/or urinary incontinence, in addition to persistent orthostatic hypotension, had a poorer prognosis compared to those with isolated persistent orthostatic hypotension or no orthostatic hypotension (Log rank x(2 = 6.370, p = 0.041. DISCUSSION: According to our findings, the identification of autonomic dysfunction seems to be of great importance in clinical practice, not only to

  12. Functional evaluation of cerebral cortex in dementia with Lewy bodies.

    Science.gov (United States)

    Di Lazzaro, Vincenzo; Pilato, Fabio; Dileone, Michele; Saturno, Eleonora; Profice, Paolo; Marra, Camillo; Daniele, Antonio; Ranieri, Federico; Quaranta, Davide; Gainotti, Guido; Tonali, Pietro A

    2007-08-15

    Neurochemical investigations have demonstrated central cholinergic dysfunction in patients with dementia with Lewy bodies (DLB). Central cholinergic circuits of the human brain can be tested non-invasively by coupling peripheral nerve stimulation with transcranial magnetic stimulation of the contralateral motor cortex. This test, named short latency afferent inhibition has been shown in healthy subjects to be sensitive to the blockage of muscarinic acetylcholine receptors and it is impaired in patients with Alzheimer disease (AD), a cholinergic form of dementia, while it is normal in non-cholinergic forms of dementia such as fronto-temporal dementia. We evaluated short latency afferent inhibition in a group of patients with DLB and compared the data with that from a group of AD patients and a control group of age-matched healthy individuals. Short latency afferent inhibition was significantly reduced in DLB and AD patients. The findings suggest that this method can be used as a non-invasive test for the assessment of cholinergic pathways in patients with dementia and may represent a useful additional tool for discriminating between cholinergic and non-cholinergic forms of dementia.

  13. Psychological distress in informal caregivers of patients with dementia in primary care: course and determinants

    NARCIS (Netherlands)

    Borsje, P.; Hems, M.A.; Lucassen, P.L.B.J.; Bor, H.; Koopmans, R.T.C.M.; Pot, A.M.

    2016-01-01

    BACKGROUND: The course of psychological distress in informal caregivers of patients with dementia has been investigated in longitudinal studies with conflicting outcomes. OBJECTIVES: We investigated the course and determinants of psychological distress in informal caregivers of patients with

  14. Overdiagnosis of Dementia in Young Patients - A Nationwide Register-Based Study

    DEFF Research Database (Denmark)

    Salem, L C; Andersen, B B; Nielsen, T R;

    2012-01-01

    Background: Little is known about the quality of the diagnostic evaluation and the validity of dementia diagnoses in young patients established in routine clinical practice. The aim of this study was to investigate the validity of the diagnosis of dementia registered in the Danish nationwide...

  15. The use of medroxyprogesterone acetate for the treatment of sexually inappropriate behaviour in patients with dementia

    Science.gov (United States)

    Light, Stacy Anderson; Holroyd, Suzanne

    2006-01-01

    Sexually inappropriate behaviour in a patient with dementia can be a problem for caregivers. Little research has been done concerning treatment for this behavioural disorder. The hormone medroxyprogesterone acetate (MPA) is a known, but infrequently used, treatment option. We describe a series of 5 cases in which MPA was used successfully to control inappropriate sexual behaviours in men with dementia. PMID:16575429

  16. Stress and Burden among Caregivers of Patients with Lewy Body Dementia

    Science.gov (United States)

    Leggett, Amanda N.; Zarit, Steven; Taylor, Angela; Galvin, James E.

    2011-01-01

    Purpose: Patients with Lewy body dementia (LBD) may present a unique set of symptoms and challenges to family caregivers compared with other types of dementia. Prominent difficulties include motor impairment, activities of daily living (ADLs) disability, recurrent behavioral and emotional problems (BEPs), and diagnostic difficulties. These…

  17. Association between hypoglycemia and dementia in patients with type 2 diabetes.

    Science.gov (United States)

    Sheen, Yi-Jing; Sheu, Wayne H H

    2016-06-01

    In addition to increased risks of macrovascular and microvascular complications, patients with type 2 diabetes mellitus (T2DM) usually also are at increased risk for cognitive impairment and dementia. Hypoglycemia, a common consequence of diabetes treatment, is considered an independent risk factor for dementia in patients with T2DM. Hypoglycemia and dementia are clinically underestimated and are related to poor outcomes; thus, they may compromise the life expectancy of patients with T2DM. Epidemiological evidence of hypoglycemia-associated cognitive decline and dementia is highly varied. Acute, severe hypoglycemic episodes induce chronic subclinical brain damage, cognitive decline, and subsequent dementia. However, the effects of recurrent moderate hypoglycemia on cognitive decline and dementia remain largely uninvestigated. Poor glycemic control (including fluctuation of hemoglobin A1C [HbA1c] and glucose values) and the viscous circle of bidirectional associations between dementia and hypoglycemia may be clinically relevant. The possible pathophysiological hypotheses include post-hypoglycemic neuronal damage, inflammatory processes, coagulation defects, endothelial abnormalities, and synaptic dysfunction of hippocampal neurons during hypoglycemia episodes. This article reviews previous findings, provides insight into the detection of groups at high risk of hypoglycemia-associated dementia, and proposes specific strategies to minimize the potential burdens associated with hypoglycemia-related neurocognitive disorders in patients with T2DM.

  18. Assessment of dementia in ethnic minority patients in Europe: a European Alzheimer's Disease Consortium survey

    DEFF Research Database (Denmark)

    Nielsen, T Rune; Vogel, Asmus; Riepe, Matthias W;

    2011-01-01

    In most European countries the ethnic minority migrant populations are currently reaching an age where dementia becomes an increasingly important issue. There is no European consensus on good clinical practice with these patient groups, who often have special needs and expectations with regard...... to dementia services....

  19. Collage as a Therapeutic Modality for Reminiscence in Patients with Dementia

    Science.gov (United States)

    Woolhiser Stallings, Jessica

    2010-01-01

    Traditional therapy, with its emphasis on verbal communication between therapist and client, may not be appropriate for patients with dementia due to impaired cognitive and verbal abilities. This brief report presents a qualitative study on the use of collage in art therapy to aid in the process of reminiscence in individuals with dementia. Data…

  20. Barriers, motivators, and facilitators of physical activity in dementia patients: A systematic review.

    Science.gov (United States)

    van Alphen, Helena J M; Hortobágyi, Tibor; van Heuvelen, Marieke J G

    2016-01-01

    Physical activity (PA) has the potential to slow the progression of dementia patients' cognitive and physical decline. A better understanding of the factors that facilitate or hamper dementia patients' PA participation will increase the success rate of implementing PA in dementia patients' daily care. We systematically screened the barriers, motivators, and facilitators of PA participation in dementia patients, complementing previous analyses of quantitative correlates of PA in community-dwelling dementia patients. Systematic searches yielded 78 potential studies of which seven met the eligibility criteria including 39 dementia patients and 36 caregivers (33 spouses and three daughters). We identified 35 barriers, 26 motivators, and 21 facilitators related to PA. We reduced these factors to six themes within the social-ecological model. Prominent barriers to PA were physical and mental limitations and difficulties with guidance and organization of PA by caregivers. Motivators included the motivation to maintain physical and mental health and participate in preferred PA options. Facilitators included strategies to avoid health problems, providing support and guidance for PA, and access to convenient and personalized PA options. The emerging picture suggests that dementia patients' PA participation will increase if service providers become familiar with the health benefits of PA, the characteristics of PA programs, methods of delivery, and the concepts of how such programs can be personalized to and synchronized with patients' individual needs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Ambulatory health services utilization in patients with dementia - Is there an urban-rural difference?

    Directory of Open Access Journals (Sweden)

    Glaeske Gerd

    2010-11-01

    Full Text Available Abstract Background Due to demographic changes and an un-equal distribution of physicians, regional analyses of service utilization of elderly patients are crucial, especially for diseases with an impact like dementia. This paper focuses on dementia patients. The aim of the study is to identify differences in service utilization of incident dementia patients in urban and rural areas. Methods Basis for the analysis were all insured persons of a German Health Insurance fund (the GEK aged 65 years and older living in rural and urban areas. We focussed on physician contacts in the outpatient sector during the first year after an incidence diagnosis of dementia. Special attention was given to contacts with primary care physicians and neurologists/psychiatrists. The dementia cohort was analyzed together with a non-dementia control group drawn according to age, gender and amount of physician contacts. Uni- and bivariate as well as multivariate analysis were performed to estimate the influences on service utilization. Results Results show that the provision of primary care seems to be equally given in urban and rural areas. For specialists contacts however, rural patients are less likely to consult neurologists or psychiatrists. This trend can already be seen before the incident diagnosis of dementia. All consultations rise in the quarter of the incident dementia diagnosis compared to the control group. The results were also tested in a linear and a logistic regression, showing a higher chance for persons living in urban areas to visit a specialist and an overall higher rate in service utilization for dementia patients. Conclusions Because of a probable increase in the number of dementia patients, service provision has to be accessible even in rural areas. Due to this and the fact that demographic change is happening at different paces in different regions, regional variations have to be considered to ensure the future service provision.

  2. Psychotropic drug prescription in nursing home patients with dementia : influence of environmental correlates and staff distress on physicians' prescription behavior

    NARCIS (Netherlands)

    Zuidema, Sytse U; de Jonghe, Jos F M; Verhey, Frans R J; Koopmans, Raymond T C M