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.

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.

Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration.

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Seo, Sang Won; Thibodeau, Marie-Pierre; Perry, David C; Hua, Alice; Sidhu, Manu; Sible, Isabel; Vargas, Jose Norberto S; Gaus, Stephanie E; Rabinovici, Gil D; Rankin, Katherine D; Boxer, Adam L; Kramer, Joel H; Rosen, Howard J; Gorno-Tempini, Maria Luisa; Grinberg, Lea T; Huang, Eric J; DeArmond, Stephen J; Trojanowski, John Q; Miller, Bruce L; Seeley, William W

2018-03-20

To examine clinicopathologic correlations in early vs late age at onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD). All patients were clinically evaluated and prospectively diagnosed at the UCSF Memory and Aging Center. Two consecutive series were included: (1) patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort 1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of the clinical syndrome (cohort 2). These series were divided by age at symptom onset (cutoff 65 years). In cohort 1, 48 (25.3%) were 65 years or older at symptom onset. Pathologic causes of behavioral variant FTD (bvFTD) were similar in the early age at onset (EO) and late age at onset (LO) bvFTD groups. In corticobasal syndrome (CBS), however, the most common pathologic substrate differed according to age at onset: progressive supranuclear palsy (42.9%) in LO-CBS and Alzheimer disease (AD; 40.7%) in EO-CBS. In cohort 2, 57 (28.4%) were classified as LO-FTLD. Regarding FTLD major molecular classes, FTLD with transactive response DNA-binding protein of 43 kDa was most common in EO-FTLD (44.4%), whereas FTLD-tau (58.3%) was most common in LO-FTLD. Antemortem diagnosis of a non-FTD syndrome, usually AD-type dementia, was more frequent in LO-FTLD than EO-FTLD (19.3% vs 7.7%, p = 0.017). LO-FTLD was also associated with more prevalent comorbid pathologic changes. Of these, moderate to severe AD neuropathologic change and argyrophilic grain disease were overrepresented among patients who received an antemortem diagnosis of AD-type dementia. Patients with FTD and FTLD often develop symptoms after age 65, and age at onset represents an important consideration when making antemortem neuropathologic predictions. © 2018 American Academy of Neurology.

Frontotemporal dementia and its subtypes

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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...

[Pathological gambling and epilepsy in patients with frontotemporal dementia: Two case reports].

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Castro-Suarez, Sheila; Martinez, Peggy; Meza, María

2016-01-01

Frontotemporal dementia is a neurodegenerative disorder of which the behavioral variant is most common. This condition is currently considered the most common cause of dementia in people younger than 60 years. Here, we present two unrelated cases in which the typical symptoms were cognitive and behavioral progressive deterioration and psychiatric disorders such as disinhibition, impulsive acts, apathy, lack of empathy, stereotypies, and changes in eating habits. The first case exhibited pathological gambling as the initial symptom and resided in a psychiatric facility for a year. Notably, this was the second such case in Latin America and one of only a few such cases reported worldwide. The second case presented with epileptic seizures during evolution. In both cases, brain magnetic resonance revealed left-predominant frontotemporal atrophy, and alterations in executive function were evident during neuropsychological assessments.

Are we comparing frontotemporal dementia and Alzheimer disease patients with the right measures?

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Deutsch, Mariel B; Liang, Li-Jung; Jimenez, Elvira E; Mather, Michelle J; Mendez, Mario F

2016-09-01

Clinical research studies of behavioral variant frontotemporal dementia (bvFTD) often use Alzheimer disease (AD) as a comparison group for control of dementia variables, using tests of cognitive function to match the groups. These two dementia syndromes, however, are very different in clinical manifestations, and the comparable severity of these dementias may not be reflected by commonly used cognitive scales such as the Mini-Mental State Examination (MMSE). We evaluated different measures of dementia severity and symptoms among 20 people with bvFTD compared to 24 with early-onset AD. Despite similar ages, disease-duration, education, and cognitive performance on two tests of cognitive function, the MMSE and the Montreal Cognitive Assessment (MoCA), the bvFTD participants, compared to the AD participants, were significantly more impaired on other measures of disease severity, including function (Functional Assessment Questionnaire (FAQ)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)), and global dementia stage (Clinical Dementia Rating Scales (CDRs)). However, when we adjusted for the frontotemporal lobar degeneration-CDR (FTLD-CDR) in the analyses, the two dementia groups were comparable across all measures despite significant differences on the cognitive scales. We found tests of cognitive functions (MMSE and MoCA) to be insufficient measures for ensuring comparability between bvFTD and AD groups. In clinical studies, the FTLD-CDR, which includes additional language and behavior items, may be a better overall way to match bvFTD and AD groups on dementia severity.

Manic behavior and asymmetric right frontotemporal dementia from a novel progranulin mutation

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Mendez MF

2018-02-01

Full Text Available Mario F Mendez1–3 1Department of Neurology, 2Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; 3Neurology Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Abstract: Studies suggest a relationship of manic behavior and bipolar disorder (BD with behavioral variant frontotemporal dementia (bvFTD. The nature of this relationship is unclear. This report presents a patient with initial manic behavior as the main manifestation of familial bvFTD from a novel progranulin (GRN mutation. In contrast, there are other reports of a long background of BD preceding a diagnosis of bvFTD. A review of the literature and this patient suggest that manic symptoms result from damage to right frontotemporal neural structures from longstanding BD, as well as from bvFTD and other focal neurological disorders. In addition, there is a subgroup of patients with a probable genetic predisposition to both BD and bvFTD. Keywords: frontotemporal dementia, mania, bipolar disorder, progranulin mutation

Clinical update on frontotemporal dementia: diagnosis and treatment.

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Mocellin, Ramon; Scholes, Amelia; Walterfang, Mark; Looi, Jeffrey C L; Velakoulis, Dennis

2015-10-01

To provide a clinical update for general psychiatrists on frontotemporal dementias (FTDs) using a selective narrative review of recent findings and advances in conceptualising, diagnosing and treating FTD. General psychiatrists can apply their skills to support patients, carers, GPs and allied health workers in comprehensive care of persons with FTD. © The Royal Australian and New Zealand College of Psychiatrists 2015.

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

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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.

Frontotemporal Dementia Complicated by Comorbid Borderline Personality Disorder: A Case Report

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Salzbrenner, LCDR Stephen; Brown, Jaime; Hart, Gavin; Dettmer, Ens Jonathan; Williams, LT Raquel; Ormeno, LT Monica; O’Neal, LCDR Ethel; Shippy, LT Jennifer

2009-01-01

Frontotemporal dementia is the fourth most common cause of dementia in the United States and characteristically presents with an early decline in social conduct, impaired regulation of interpersonal conduct, emotional blunting, and general loss of insight, with relative preservation of memory. This a case of frontotemporal dementia in a 46-year-old woman who presented with existing diagnoses of borderline personality disorder and major depressive disorder. She had been repeatedly evaluated fo...

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

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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.

Restoring neuronal progranulin reverses deficits in a mouse model of frontotemporal dementia.

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Arrant, Andrew E; Filiano, Anthony J; Unger, Daniel E; Young, Allen H; Roberson, Erik D

2017-05-01

Loss-of-function mutations in progranulin (GRN), a secreted glycoprotein expressed by neurons and microglia, are a common autosomal dominant cause of frontotemporal dementia, a neurodegenerative disease commonly characterized by disrupted social and emotional behaviour. GRN mutations are thought to cause frontotemporal dementia through progranulin haploinsufficiency, therefore, boosting progranulin expression from the intact allele is a rational treatment strategy. However, this approach has not been tested in an animal model of frontotemporal dementia and it is unclear if boosting progranulin could correct pre-existing deficits. Here, we show that adeno-associated virus-driven expression of progranulin in the medial prefrontal cortex reverses social dominance deficits in Grn+/- mice, an animal model of frontotemporal dementia due to GRN mutations. Adeno-associated virus-progranulin also corrected lysosomal abnormalities in Grn+/- mice. The adeno-associated virus-progranulin vector only transduced neurons, suggesting that restoring neuronal progranulin is sufficient to correct deficits in Grn+/- mice. To further test the role of neuronal progranulin in the development of frontotemporal dementia-related deficits, we generated two neuronal progranulin-deficient mouse lines using CaMKII-Cre and Nestin-Cre. Measuring progranulin levels in these lines indicated that most brain progranulin is derived from neurons. Both neuronal progranulin-deficient lines developed social dominance deficits similar to those in global Grn+/- mice, showing that neuronal progranulin deficiency is sufficient to disrupt social behaviour. These data support the concept of progranulin-boosting therapies for frontotemporal dementia and highlight an important role for neuron-derived progranulin in maintaining normal social function. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Psychosis in behavioral variant frontotemporal dementia

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Gossink FT

2017-04-01

Full Text Available Flora T Gossink,1,2 Everard GB Vijverberg,2,3 Welmoed Krudop,2 Philip Scheltens,2 Max L Stek,1 Yolande AL Pijnenburg,1,2 Annemiek Dols1,2 1Department of Old Age Psychiatry, GGZinGeest, 2Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, 3Department of Neurology, HagaZiekenhuis, The Hague, the Netherlands Background: Dementia is generally characterized by cognitive impairment that can be accompanied by psychotic symptoms; for example, visual hallucinations are a core feature of dementia with Lewy bodies, and delusions are often seen in Alzheimer’s disease. However, for behavioral variant of frontotemporal dementia (bvFTD, studies on the broad spectrum of psychotic symptoms are still lacking. The aim of this study was to systematically and prospectively subtype the wide spectrum of psychotic symptoms in probable and definite bvFTD.Methods: In this study, a commonly used and validated clinical scale that quantifies the broad spectrum of psychotic symptoms (Positive and Negative Symptom Scale was used in patients with probable and definite bvFTD (n=22 and with a primary psychiatric disorder (n=35 in a late-onset frontal lobe cohort. Median symptom duration was 2.8 years, and the patients were prospectively followed for 2 years.Results: In total, 22.7% of bvFTD patients suffered from delusions, hallucinatory behavior, and suspiciousness, although the majority of the patients exhibited negative psychotic symptoms such as social and emotional withdrawal and blunted affect (95.5% and formal thought disorders (81.8%. “Difficulty in abstract thinking” and “stereotypical thinking” (formal thought disorders differentiated bvFTD from psychiatric disorders. The combined predictors difficulty in abstract thinking, stereotypical thinking, “anxiety”, “guilt feelings,” and “tension” explained 75.4% of variance in the diagnosis of bvFTD versus psychiatric diagnoses (P<0.001.Conclusion: Delusions

Genetics Home Reference: GRN-related frontotemporal dementia

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... making a protein called granulin (also known as progranulin). Granulin is active in many different tissues in ... Boeve B, Feldman H, Hutton M. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome ...

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.

SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis.

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Le Ber, Isabelle; Camuzat, Agnès; Guerreiro, Rita; Bouya-Ahmed, Kawtar; Bras, Jose; Nicolas, Gael; Gabelle, Audrey; Didic, Mira; De Septenville, Anne; Millecamps, Stéphanie; Lenglet, Timothée; Latouche, Morwena; Kabashi, Edor; Campion, Dominique; Hannequin, Didier; Hardy, John; Brice, Alexis

2013-11-01

Mutations in the SQSTM1 gene, coding for p62, are a cause of Paget disease of bone and amyotrophic lateral sclerosis (ALS). Recently, SQSTM1 mutations were confirmed in ALS, and mutations were also identified in 3 patients with frontotemporal dementia (FTD), suggesting a role for SQSTM1 in FTD. To evaluate the exact contribution of SQSTM1 to FTD and FTD with ALS (FTD-ALS) in an independent cohort of patients. A SQSTM1 mutation was first identified in a multiplex family with FTD by use of whole-exome sequencing. To evaluate the frequency of SQSTM1 mutations, we sequenced this gene in a cohort of patients with FTD or FTD-ALS, with no mutations in known FTD and ALS genes. Primary care or referral center. An overall cohort of 188 French patients, including 132 probands with FTD and 56 probands with FTD-ALS. Frequency of SQSTM1 mutations in patients with FTD or FTD-ALS; description of associated phenotypes. We identified 4 heterozygous missense mutations in 4 unrelated families with FTD; only 1 family had clinical symptoms of Paget disease of bone, and only 1 family had clinical symptoms of FTD-ALS, possibly owing to the low penetrance of some of the clinical manifestations. Although the frequency of the mutations is low in our series (4 of 188 patients [2%]), our results, similar to those already reported, support a direct pathogenic role of p62 in different types of FTD.

From narcissistic personality disorder to frontotemporal dementia: a case report.

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Poletti, Michele; Bonuccelli, Ubaldo

2011-01-01

Premorbid personality characteristics could have a pathoplastic effect on behavioral symptoms and personality changes related to neurodegenerative diseases. Patients with personality disorders, in particular of the dramatic cluster, may present functional frontolimbic abnormalities. May these neurobiological vulnerabilities linked to a premorbid personality disorder predispose or represent a risk factor to subsequently develop a neurodegenerative disorder? Are subjects with personality disorders more at risk to develop a dementia than mentally healthy subjects? This topic is discussed presenting the clinical case of a patient who suffered of a probable Narcissistic Personality Disorder and subsequently developed a clinically diagnosed Frontotemporal Dementia.

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

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Binnewijzend, Maja A.A.; Wattjes, Mike P.; Berckel, Bart N.M. van; Barkhof, Frederik; Kuijer, Joost P.A.; Flier, Wiesje M. van der; Benedictus, Marije R.; Moeller, Christiane M.; Pijnenburg, Yolande A.L.; Lemstra, Afina W.; Prins, Niels D.; Scheltens, Philip

2014-01-01

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.)

PROGRANULIN MUTATIONS AFFECTS BRAIN OSCILLATORY ACTIVITY IN FRONTO-TEMPORAL DEMENTIA

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Davide Vito Moretti

2016-02-01

Full Text Available Background: mild cognitive impairment (MCI is a clinical stage indicating a prodromal phase of dementia. This practical concept could be used also for fronto-temporal dementia (FTD. Progranulin (PGRN has been recently recognized as a useful diagnostic biomarker for fronto-temporal lobe degeneration (FTLD due to GRN null mutations. Electroencephalography (EEG is a reliable tool in detecting brain networks changes. The working hypothesis of the present study is that EEG oscillations could detect different modifications among FTLD stages (FTD-MCI versus overt FTD as well as differences between GRN mutation carriers versus non carriers in patients with overt FTD. Methods: EEG in all patients and PGRN dosage in patients with a clear FTD were detected. The cognitive state has been investigated through mini mental state examination (MMSE. Results: MCI-FTD showed a significant lower spectral power in both alpha and theta oscillations as compared to overt FTD. GRN mutations carriers affected by FTLD show an increase in high alpha and decrease in theta oscillations as compared to non-carriers.Conclusion: EEG frequency rhythms are sensible to different stage of FTD and could detect changes in brain oscillatory activity affected by GRN mutations

Frontotemporal Degeneration in a Child.

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Terrill, Tyler; Pascual, Juan M

2017-07-01

There is a predilection for the frontal and temporal lobes in certain cases of dementia in the adult, leading to the syndrome of frontotemporal dementia. However, this syndrome has seemed to elude the developing brain until now. We describe an example of apparently selective neurodegeneration of the frontal and temporal regions during development associated with some of the clinical, magnetic resonance imaging, and fludeoxyglucose positron emission tomography (FDG PET) scan features of canonical frontotemporal dementia in the adult. This patient does not have any of the common frontotemporal dementia-causing mutations or known progressive brain disorders of children. This patient illustrates that symptomatic, selective, and progressive vulnerability of the frontal and temporal lobes is not restricted to adulthood, expanding the phenotype of frontotemporal degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

The Power of Neuroimaging Biomarkers for Screening Frontotemporal Dementia

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McMillan, Corey T.; Avants, Brian B.; Cook, Philip; Ungar, Lyle; Trojanowski, John Q.; Grossman, Murray

2014-01-01

Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative disease that can result from either frontotemporal lobar degeneration (FTLD) or Alzheimer’s disease (AD) pathology. It is critical to establish statistically powerful biomarkers that can achieve substantial cost-savings and increase feasibility of clinical trials. We assessed three broad categories of neuroimaging methods to screen underlying FTLD and AD pathology in a clinical FTD series: global ...

Coexistence of Schizophrenia and Frontotemporal Dementia: A Case Report

OpenAIRE

Zafer Subasi

2014-01-01

With this case, it is aimed to present a patient who was followed up with a diagnosis of schizophrenia nearly 30 years, had personality and behaviour changes added to clinical course for the last 4-5 years, had diagnostic confusion and was finally diagnosed with frontotemporal dementia superimposed on schizophrenia.Neurodegenerative diseases should be considered as either differential diagnosis or coexistence in case of symptoms such as cognitive decline or personality and behavior changes oc...

Efficacy of Electroconvulsive Therapy for Comorbid Frontotemporal Dementia with Bipolar Disorder

OpenAIRE

Paul, Sean; Goetz, Jennifer; Bennett, Jeffrey; Korah, Tessy

2013-01-01

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.

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...

[Usefulness of the Addenbrooke's Cognitive Examination (Spanish version) in Peruvian patients with Alzheimer's disease and Frontotemporal Dementia].

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Custodio, Nilton; Lira, David; Montesinos, Rosa; Gleichgerrcht, Ezequiel; Manes, Facundo

2012-01-01

The development of screening tools for the assessment of cognitive status in patients with dementia must be brief yet both highly sensitive and specific in order to ensure its clinical utility. In this sense, it is important to adapt tools widely used around the world to particular populations, allowing for a more proper validity of its use in everyday clinical practice. One of the most popular general cognitive screening tools is the Addenbrooke's Cognitive Examination (ACE), which has been adapted and validated in multiple languages and populations. To assess the usefulness of the Peruvian version of the ACE in patients with dementia. Healthy controls, patients with Alzheimer disease (AD) and patients with Frontotemporal Dementia (FTD) were assessed with the Peruvian version of the ACE, the ADAScog to determine dementia severity, and a complete neuropsychological battery. The Peruvian version of the ACE showed very good internal consistency, strong concurrent validity as revealed by significant correlations between the ACE total score and both the MMSE and ADAScog. The ACE was able to differentiate healthy controls from patients with dementia with high discriminatory accuracy. Using a cut-off score of 86 (out of 100), the ACE was exhibited a sensitivity of 100% and a specificity of 100%.

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

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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.)

Frontotemporal dementia and primary progressive aphasia, a review

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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

Efficacy of Electroconvulsive Therapy for Comorbid Frontotemporal Dementia with Bipolar Disorder

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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.

Late onset bipolar disorder and frontotemporal dementia with mutation in progranulin gene: a case report.

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Rubino, Elisa; Vacca, Alessandro; Gallone, Salvatore; Govone, Flora; Zucca, Milena; Gai, Annalisa; Ferrero, Patrizia; Fenoglio, Pierpaola; Giordana, Maria Teresa; Rainero, Innocenzo

2017-11-01

Bipolar disorder is a chronic psychiatric illness characterised by fluctuation in mood state, with a relapsing and remitting course. Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous syndrome, with the most frequent phenotype being behavioural variant frontotemporal dementia (bvFTD). Here, we report the case of an Italian male presenting with late-onset bipolar disorder that developed into bvFTD over time, carrying a mutation in the GRN gene. Interestingly, the patient carried the c.1639 C > T variant in the GRN gene, resulting in a R547C substitution. Our case report further corroborates the notion that, in addition to FTD, progranulin may be involved in the neurobiology of bipolar disorder type 1, and suggests to screen patients with late-onset bipolar disorder for GRN mutations.

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...

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

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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.

Quantitative Balance and Gait Measurement in Patients with Frontotemporal Dementia and Alzheimer Diseases: A Pilot Study.

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Velayutham, Selva Ganapathy; Chandra, Sadanandavalli Retnaswami; Bharath, Srikala; Shankar, Ravi Girikamatha

2017-01-01

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. 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 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. 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. 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.

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

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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; Pde Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

TREM2 mutations are rare in a French cohort of patients with frontotemporal dementia.

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Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Dayan, Sarah; Godard, Chloé; Van Bortel, Inge; De Septenville, Anne; Ciura, Sorana; Brice, Alexis; Kabashi, Edor

2013-10-01

Homozygous mutations in TREM2 have been recently identified by exome sequencing in families presenting with frontotemporal dementia (FTD)-like phenotype. No study has evaluated the exact frequency of TREM2 mutations in cohorts of FTD patients so far. We sequenced TREM2 in 175 patients with pure FTD, mostly French, to test whether mutations could be implicated in the pathogenesis of the disease. No disease-causing mutation was identified in 175 individuals from the French cohort of FTD patients. We did not identify the polymorphism p.R47H (rs75932628), strongly associated with an increased risk of developing Alzheimer's disease. We conclude that TREM2 mutations are extremely rare in patients with pure FTD, although further investigation in larger populations is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Current Role for Biomarkers in Clinical Diagnosis of Alzheimer Disease and Frontotemporal Dementia.

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Sheikh-Bahaei, Nasim; Sajjadi, Seyed Ahmad; Pierce, Aimee L

2017-11-14

Purpose of review Alzheimer's disease (AD) and frontotemporal dementia can often be diagnosed accurately with careful clinical history, cognitive testing, neurological examination, and structural brain MRI. However, there are certain circumstances wherein detection of specific biomarkers of neurodegeneration or underlying AD pathology will impact the clinical diagnosis or treatment plan. We will review the currently available biomarkers for AD and frontotemporal dementia (FTD) and discuss their clinical importance. Recent findings With the advent of 18 F-labeled tracers that bind amyloid plaques, amyloid PET is now clinically available for the detection of amyloid pathology and to aid in a biomarker-supported diagnosis of AD or mild cognitive impairment (MCI) due to AD. It is not yet possible to test for the specific FTD pathologies (tau or TDP-43); however, a diagnosis of FTD may be "imaging supported" based upon specific MRI or FDG-PET findings. Cerebrospinal fluid measures of amyloid-beta, total-tau, and phospho-tau are clinically available and allow detection of both of the cardinal pathologies of AD: amyloid and tau pathology. Summary It is appropriate to pursue biomarker testing in cases of MCI and dementia when there remains diagnostic uncertainty and the result will impact diagnosis or treatment. Practically speaking, due to the rising prevalence of amyloid positivity with advancing age, measurement of biomarkers in cases of MCI and dementia is most helpful in early-onset patients, patients with atypical clinical presentations, or when considering referral for AD clinical trials.

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

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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.

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

Cerebrospinal Fluid Biomarkers in Familial Forms of Alzheimer's Disease and Frontotemporal Dementia

DEFF Research Database (Denmark)

Rostgaard, Nina; Waldemar, Gunhild; Nielsen, Jørgen Erik

2015-01-01

As dementia is a fast-growing health care problem, it is becoming an increasingly urgent need to provide an early diagnosis in order to offer patients the best medical treatment and care. Validated biomarkers which reflect the pathology and disease progression are essential for diagnosis and are ......As dementia is a fast-growing health care problem, it is becoming an increasingly urgent need to provide an early diagnosis in order to offer patients the best medical treatment and care. Validated biomarkers which reflect the pathology and disease progression are essential for diagnosis...... and are important when developing new therapies. Today, the core protein biomarkers amyloid-β42, total tau and phosphorylated tau in the cerebrospinal fluid (CSF) are used to diagnose Alzheimer's disease (AD), because these biomarkers have shown to reflect the underlying amyloid and tau pathology. However......, the biomarkers have proved insufficient predictors of dementias with a different pathology, e.g. frontotemporal dementia (FTD); furthermore, the biomarkers are not useful for early AD diagnosis. Familial dementias with a known disease-causing mutation can be extremely valuable to study; yet the biomarker...

Sensitivity of current criteria for the diagnosis of behavioral variant frontotemporal dementia

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Piguet, O; Hornberger, M; Shelley, B P.; Kipps, C M.; Hodges, J R.

2009-01-01

Background: Diagnosis of behavioral variant frontotemporal dementia (bvFTD) relies on criteria that are constraining and potentially ambiguous. Some features are open to clinical interpretation and their prevalence unknown. This study investigated the sensitivity of current diagnostic criteria in a large group of patients with bvFTD. Methods: Forty-five patients with clear evidence of bvFTD as judged by progressive clinical decline (>3 years) with marked frontal features and significant frontal brain atrophy on brain MRI were included. Thirty-two have died; pathologic confirmation of frontotemporal lobar degeneration was found in all 18 coming to autopsy. We established the prevalence of core and supportive diagnostic features at presentation and with disease progression. Results: Only 25/45 patients (56%) showed all five core features necessary for a diagnosis of bvFTD at initial presentation and 33/45 (73%) as their disease progressed. Two core features, emotional blunting and loss of insight, were never observed in 25% and 13% of cases. Executive dysfunction, hyperorality, mental inflexibility, and distractibility were the only supportive features present in >50% of cases at initial presentation. Although not a diagnostic feature, impaired activities of daily living was present in 33/45 patients (73%). Conclusions: Strict application of the criteria misses a significant proportion of patients. Many supportive features have low prevalence and are clinically not useful. Revision of the criteria to include level of certainty (definite, probable, possible) dependent on the number of features present and the presence of ancillary information (e.g., brain atrophy, neuropsychological abnormalities, impaired activities of daily living) is encouraged. GLOSSARY ACE = Addenbrooke’s Cognitive Examination; ADL = activities of daily living; bvFTD = behavioral variant frontotemporal dementia; MMSE = Mini-Mental State Examination. PMID:19237702

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.

Perception of emotion in frontotemporal dementia and Alzheimer disease.

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Lavenu, I; Pasquier, F; Lebert, F; Petit, H; Van der Linden, M

1999-01-01

Frontotemporal dementia (FTD) is the second cause of degenerative dementia. Behavioral changes occur before the cognitive decline and remain the major feature. A poor perception of emotion could account for some behavioral symptoms. The aim of this study was to assess the perception of emotion in patients with FTD and to compare it with that of patients with Alzheimer disease (AD). Fifty subjects performed the tests: 20 patients with probable AD, 18 patients with FTD, and 12 matched controls. The two patient groups did not differ in age, sex, severity of dementia, duration of the disease, and language tests. Subjects had to recognize and point out the name of one of seven basic emotions (anger, disgust, happiness, fear, sadness, surprise, and contempt) on a set of 28 faces presented on slides. The three groups were equally able to distinguish a face displaying affect from one not displaying affect. Naming of emotion was worse in patients with FTD than in patients with AD (correct answers 46% vs. 62%; p = 0.0006) who did not differ significantly from controls (72%). Anger, sadness, and disgust were less recognized in FTD than in AD patients who did not differ from controls, whereas fear and contempt were poorly recognized in both groups of patients compared with controls. These findings argue for different neural substrates underlying the recognition of various basic emotions. Behavioral disorders in FTD may be partly due to an impaired interpretation of the emotional environment.

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

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

2017-05-01

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. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

NARCIS (Netherlands)

Majounie, E.; Renton, A.E.; Mok, K.; Dopper, E.G.P.; Waite, A.; Rollinson, S.; Chio, A.; Restagno, G.; Nicolaou, N.; Simon-Sanchez, J.; van Swieten, J.C.; Abramzon, Y.; Johnson, J.O.; Sendtner, M.; Pamphlett, R.; Orrell, R.W.; Mead, S.; Sidle, K.C.; Houlden, H.; Rohrer, J.D.; Morrison, K.E.; Pall, H.; Talbot, K.; Ansorge, O.; Hernandez, D.G.; Arepalli, S.; Sabatelli, M.; Mora, G.; Corbo, M.; Giannini, F.; Calvo, A.; Englund, E.; Borghero, G.; Foris, G.L.; Remes, A.M.; Laaksovirta, H.; McCluskey, L.; Trojanowski, J.Q.; Van Deerlin, V.M.; Schellenberg, G.D.; Nalls, M.A.; Drory, V.E.; Lu, C.S.; Yeh, T.H.; Ishiura, H.; Takahashi, Y.; Tsuji, S.; Le Ber, I.; Brice, A.; Drepper, C.; Williams, N.; Kirby, J.; Shaw, P.; Hardy, J.; Tienari, P.J.; Heutink, P.; Morris, H.R.; Pickering-Brown, S.; Traynor, B.J.

2012-01-01

Background: 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 ALS (El

Person-Based Versus Generalized Impulsivity Disinhibition in Frontotemporal Dementia and Alzheimer Disease.

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Paholpak, Pongsatorn; Carr, Andrew R; Barsuglia, Joseph P; Barrows, Robin J; Jimenez, Elvira; Lee, Grace J; Mendez, Mario F

2016-09-19

While much disinhibition in dementia results from generalized impulsivity, in behavioral variant frontotemporal dementia (bvFTD) disinhibition may also result from impaired social cognition. To deconstruct disinhibition and its neural correlates in bvFTD vs. early-onset Alzheimer's disease (eAD). Caregivers of 16 bvFTD and 21 matched-eAD patients completed the Frontal Systems Behavior Scale disinhibition items. The disinhibition items were further categorized into (1) "person-based" subscale which predominantly associated with violating social propriety and personal boundary and (2) "generalized-impulsivity" subscale which included nonspecific impulsive acts. Subscale scores were correlated with grey matter volumes from tensor-based morphometry on magnetic resonance images. In comparison to the eAD patients, the bvFTD patients developed greater person-based disinhibition (P dementia, violations of social propriety and personal boundaries involved fronto-parieto-temporal network of Theory of Mind, whereas nonspecific disinhibition involved the OFC and aTL. © The Author(s) 2016.

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

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

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Bertoux, Maxime; Cova, Florian; Pessiglione, Mathias; Hsu, Ming; Dubois, Bruno; Bourgeois-Gironde, Sacha

2014-01-01

The Allais Paradox represents one 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 matched controls and Alzheimer's disease (AD) patients, 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.

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

The Use of Profanity During Letter Fluency Tasks in Frontotemporal Dementia and Alzheimer's Disease

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Ringman, John M.; Kwon, Eunice; Flores, Deborah L.; Rotko, Carol; Mendez, Mario F.; Lu, Po

2012-01-01

Objective To assess whether the production of profanity during letter fluency testing distinguishes frontotemporal dementia (FTD) and Alzheimer's disease (AD) patients. Background Alterations in language and social behavior typify FTD spectrum disorders. Nonetheless, in can be difficult to distinguish pathologically-defined frontotemporal lobar degeneration (FTLD) from AD clinically. Assessing verbal fluency by having patients generate as many words as they can beginning with specific letters in a given period of time can yield diverse information of diagnostic utility. Method Words produced during FAS letter fluency testing were reviewed and instances of the use of "f*ck", "*ss", and "sh*t" and other words felt to be inappropriate were sought. The frequency of these words was compared between clinically diagnosed FTD and AD patients using chi-square tests. Results We found that 6/32 (18.8%) patients with FTD generated the word "f*ck" during the "F" trial as opposed to none of 38 patients with AD (p = 0.007). Patients who said "f*ck" had diagnoses of either behavioral variant FTD (3/15), progressive non-fluent aphasia (2/8), or semantic dementia (1/3). Conclusions Though the specific neuropathology in these cases is uncertain, generation of "f*ck" during letter fluency testing appears to have utility in differentiating FTD from AD. PMID:20829665

Dissociation between controlled and automatic processes in the behavioral variant of fronto-temporal dementia.

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Collette, Fabienne; Van der Linden, Martial; Salmon, Eric

2010-01-01

A decline of cognitive functioning affecting several cognitive domains was frequently reported in patients with frontotemporal dementia. We were interested in determining if these deficits can be interpreted as reflecting an impairment of controlled cognitive processes by using an assessment tool specifically developed to explore the distinction between automatic and controlled processes, namely the process dissociation procedure (PDP) developed by Jacoby. The PDP was applied to a word stem completion task to determine the contribution of automatic and controlled processes to episodic memory performance and was administered to a group of 12 patients with the behavioral variant of frontotemporal dementia (bv-FTD) and 20 control subjects (CS). Bv-FTD patients obtained a lower performance than CS for the estimates of controlled processes, but no group differences was observed for estimates of automatic processes. The between-groups comparison of the estimates of controlled and automatic processes showed a larger contribution of automatic processes to performance in bv-FTD, while a slightly more important contribution of controlled processes was observed in control subjects. These results are clearly indicative of an alteration of controlled memory processes in bv-FTD.

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

Exploring frontotemporal dementia through a case report: An emerging public health concern in disguise

Directory of Open Access Journals (Sweden)

Nitin Khadilkar

2015-01-01

Full Text Available Dementia has been declared by the World Health Organization as a significant public health problem around the world. Frontotemporal dementia (FTD is a lesser known, yet the second most common type of dementia among older adults under the age of 65 years. Age of onset in FTD is around late fifties, which is not typical for a diagnosis of dementia. In dementia, it is common to see psychiatric symptoms such as hallucinations or delusions as initial presentations. However, FTD may mimic mood disorders. Unfortunately, there are no definitive treatments or ways to prevent FTD. Additionally, challenges such as an earlier age of onset, delay in diagnosis, and difficulties with placement in nursing homes may be encountered while treating FTD patients. Here, we explore FTD through the case of a 61-year-old Caucasian female who initially presented with suicidal ideations.

Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17

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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.

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 ....... pronounced restlessness and mania. In this article we describe a nonpharmacological psychosocial approach, music therapy, and how it is possible to work with this method when constitutional, regulative, dialogical, and integrative aspects are included. The focus is on therapeutic singing where well......-known songs are applied in order to build up structure and stability and/or as means of arousal regulation. Songs with personal meaning make it possible to acknowledge the person's emotions, breaking the social isolation, and meeting the music therapy participant's psychosocial needs. The clinical approach...

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....... pronounced restlessness and mania. In this article we describe a non-pharmacological psychosocial approach, music therapy, and how it is possible to work with this method when constitutional, regulative, dialogical, and integrative aspects are included. The focus is on therapeutic singing where well known...... songs are applied in order to build up structure and stability and/or as means of arousal regulation. Songs with personal meaning make it possible to acknowledge the person’s emotions, breaking the social isolation, and meeting the music therapy participant’s psychosocial needs. The clinical approach...

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...... to increase when psychosocial needs are not met (Kitwood 1997). Thus there is a growing need to address psychosocial needs, while at the same time psychosocial needs are increasing difficult to help as a result of frontotemporal dementia. In frontotemporal dementia the progressive loss of cognitive...... 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...

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.

The Genetics of Monogenic Frontotemporal Dementia

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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.

Validation of the Addenbrooke's Cognitive Examination III in frontotemporal dementia and Alzheimer's disease.

Science.gov (United States)

Hsieh, Sharpley; Schubert, Samantha; Hoon, Christopher; Mioshi, Eneida; Hodges, John R

2013-01-01

The aims of this study were to validate the newly developed version of the Addenbrooke's Cognitive Examination (ACE-III) against standardised neuropsychological tests and its predecessor (ACE-R) in early dementia. A total of 61 patients with dementia (frontotemporal dementia, FTD, n = 33, and Alzheimer's disease, AD, n = 28) and 25 controls were included in the study. ACE-III cognitive domains correlated significantly with standardised neuropsychological tests used in the assessment of attention, language, verbal memory and visuospatial function. The ACE-III also compared very favourably with its predecessor, the ACE-R, with similar levels of sensitivity and specificity. The results of this study provide objective validation of the ACE-III as a screening tool for cognitive deficits in FTD and AD. © 2013 S. Karger AG, Basel.

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

BACKGROUND: Among patients with onset of dementia below the age of 65 years, frontotemporal dementia (FTD) is the second most prevalent cause, secondary only to Alzheimer's disease. Recent advances in understanding the heterogeneous genetic background for different clinical and neuropathological ...

The study of fMRI in Alzheimer's disease, frontotemporal dementia and Lewy bodies dementia

International Nuclear Information System (INIS)

Zhang Bing; Xu Jun; Xu Yun; Zhu Bin

2010-01-01

Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the main type of neuro degenerative diseases, but the FTD and DLB are always confused with AD. Structural MRI, diffusion-weighted imaging and proton magnetic resonance spectroscopy have the potential to support the diagnosis of AD and the relative disease. Brain atrophy pattern, apparent diffusion coefficient and fractional anisotropy pattern, the distribution mode of N-acetylaspartate and myo-inositol in temporal lobe, hippocampus, parietal lobe, frontal lobe could help to differentiate AD from FTD, DLB and those patterns are in accordance with the pathological changes. (authors)

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

OpenAIRE

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

2011-01-01

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 E...

Caregiver burden in atypical dementias: comparing frontotemporal dementia, Creutzfeldt-Jakob disease, and Alzheimer's disease.

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Uflacker, Alice; Edmondson, Mary C; Onyike, Chiadi U; Appleby, Brian S

2016-02-01

Caregiver burden is a significant issue in the treatment of dementia and a known contributor to institutionalization of patients with dementia. Published data have documented increased caregiver burden in behavioral variant frontotemporal dementia (bvFTD) compared to Alzheimer's disease (AD). Another atypical dementia with high-perceived caregiver burden is sporadic Creutzfeldt-Jakob disease (sCJD), but no formal studies have assessed this perception. The aim of this study was to compare caregiver burden across atypical dementia etiologies. 76 adults with atypical dementia (young-onset AD [YOAD], bvFTD, language variant FTD [lvFTD], and sCJD) were administered an abbreviated version of the Zarit Burden Interview (ZBI), Neuropsychiatric Inventory (NPI-Q), and other assessment instruments during a five-year time period at Johns Hopkins Hospital (JHH). A Cox regression model examined differences between disease categories that impact mean ZBI scores. Mean ZBI scores were significantly different between dementia etiologies, with bvFTD and sCJD having the highest caregiver burden (p = 0.026). Mean NPI-Q caregiver distress scores were highest in bvFTD and sCJD (p = 0.002), with sCJD and bvFTD also having the highest number of endorsed symptom domains (p = 0.012). On regression analyses, an interactive variable combining final diagnosis category and NPI-Q total severity score demonstrated statistically significant differences in mean ZBI scores for sCJD and bvFTD. This study demonstrates that bvFTD and sCJD have increased levels of caregiver burden, NPI-Q caregiver distress, total severity scores, and number of endorsed symptom domains. These results suggest that higher caregiver burden in bvFTD and sCJD are disease specific and possibly related to neuropsychiatric symptoms.

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

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Baldock, Deanna; Miller, Justin B; Leger, Gabriel C; Banks, Sarah Jane

2016-01-01

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. 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. 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.

Regional cerebral glucose metabolism in frontotemporal lobar degeneration

International Nuclear Information System (INIS)

Park, J.M.; Cho, S.S.; Lee, K.-H.; Choi, Y.; Choe, Y.S.; Kim, B.-T.; Kim, S.E.; Kwon, J.C.; Na, D.L.

2002-01-01

Purpose: Frontotemporal lobar degeneration (FTLD) is the third most common cause of dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neuro behavioral 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 patients with FTLD presented with four different clinical syndromes. Methods: We analyzed 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. Results: Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral pre-motor area 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 and neuropsychological features of FTLD syndromes. Conclusion: These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD

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

NARCIS (Netherlands)

R.M.E. Steketee (Rebecca); E.E. Bron (Esther); R. Meijboom (Rozanna); G.C. Houston (Gavin); S. Klein (Stefan); H.J.M.M. Mutsaerts (Henri J. M.); C. Méndez Orellana (Carolina); F.J. De Jong (Frank J.); J.C. van Swieten (John); A. van der Lugt (Aad); M. Smits (Marion)

2016-01-01

textabstractObjective: 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

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

NARCIS (Netherlands)

R.M.E. Steketee (Rebecca); E.E. Bron (Esther); Meijboom, R. (Rozanna); Houston, G.C. (Gavin C.); Klein, S. (Stefan); H.J.M.M. Mutsaerts (Henri J. M.); Orellana, C.P.M. (Carolina P. Mendez); F.J. de Jong (Fransina); J.C. van Swieten (John); A. van der Lugt (Aad); M. Smits (Marion)

2015-01-01

textabstractObjective: 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

The unique predisposition to criminal violations in frontotemporal dementia.

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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.

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

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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.

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.

Analysis on early clinical features of behavioral variant frontotemporal dementia

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Guan-jun LI

2017-11-01

Full Text Available Background Although the early behavioral symptoms of behavioral variant frontotemporal dementia (bvFTD are prominent, early diagnosis for bvFTD is difficult due to confusion with other mental disorders, and lack of sensitivity and specificity of diagnostic criteria, etc. In this paper, we summarized the important reviews in recent years and analyzed the clinical characteristics of bvFTD patients to improve the detection of early symptoms in bvFTD. Methods Twenty-three possible or probable bvFTD patients were diagnosed according to International Behavioral Variant Frontotemporal Dementia Criteria Consortium (FTDC. Self-designed questionnaires designed by Shanghai Mental Health Center were used to collect sociodemographic data and general information of patients. Their clinical characteristics were summarized, including abnormal behaviors, cognitive impairment, psychotic symptoms and other symptoms. Mini-Mental State Examination (MMSE, Activities of Daily Living (ADL and Clinical Dementia Rating Scale (CDR were used to make neuropsychological tests and compare with similar overseas studies (control group, N = 66. Results Eleven male patients and 12 female patients were included in our study. Compared with control group, the average age of onset [(50.83 ± 11.55 years vs. (57.00 ± 10.00 years; t = 3.863, P = 0.000] and average age of diagnosis [(53.22 ± 11.55 years vs. (61.00 ± 9.00 years; t = 13.423, P = 0.000] of bvFTD patients were smaller. The study showed that bvFTD patients had more apathy or indolence [95.65% (22/23 vs. 65.15% (43/66; χ2 = 8.057, P = 0.005], loss of sympathy or empathy [95.65% (22/23 vs. 33.33% (22/66; χ2 = 26.499, P = 0.000], while patients in control group showed more derepression behavior [98.48% (65/66 vs. 52.17% (12/23; χ2 = 27.514, P = 0.000] and continuous, stiff, obsessive and/or ritualized behavior [95.45% (63/66 vs. 30.43% (7/23; adjusted χ2 = 39.159, P = 0.000]. For cognitive impairment, bvFTD patients

Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases

DEFF Research Database (Denmark)

Ferrari, Raffaele; Wang, Yunpeng; Vandrovcova, Jana

2017-01-01

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...

A Case of Morvan Syndrome Mimicking Amyotrophic Lateral Sclerosis With Frontotemporal Dementia.

Science.gov (United States)

Freund, Brin; Maddali, Manoj; Lloyd, Thomas E

2016-06-01

Morvan syndrome is a rare autoimmune/paraneoplastic disorder involving antibodies to the voltage-gated potassium channel complex. It is defined by subacute encephalopathy, neuromuscular hyperexcitability, dysautonomia, and sleep disturbance. It may present a diagnostic dilemma when trying to differentiate from amyotrophic lateral sclerosis with frontotemporal dementia. A 76-year-old man with a history of untreated prostate adenocarcinoma was evaluated for subacute cognitive decline, diffuse muscle cramps, and hyponatremia. MRI demonstrated atrophy most prominent in the frontal and temporal regions. Electromyography (EMG) demonstrated diffuse myokymia/neuromyotonia. Polysomnography lacked REM and N3 sleep. Paraneoplastic panel detected antibodies to voltage-gated potassium channel complex (CASPR2 subtype). It is difficult to differentiate between Morvan syndrome and amyotrophic lateral sclerosis with frontotemporal dementia with examination and neuroimaging alone. There may be a link between Morvan syndrome and prostate adenocarcinoma which could help with screening/diagnosis. The authors found that laboratory and neurophysiological tests are indispensable in diagnosing and treating Morvan syndrome.

Diagnosis and management of behavioral variant frontotemporal dementia.

Science.gov (United States)

Pressman, Peter S; Miller, Bruce L

2014-04-01

Frontotemporal dementia was documented over a century ago. The last decade, however, has seen substantial changes in our conceptions of this increasingly recognized disorder. Different clinical variants have been delineated, the most common of which is the behavioral variant (bvFTD). Updated diagnostic criteria have been established. New histopathological findings and genetic etiologies have been discovered. Research continues to uncover molecular mechanisms by which abnormal proteins accumulate in degenerating brain tissue. Novel neuroimaging techniques suggest that functional networks are diminished in bvFTD that might be relevant to empathy and social behavior. Despite rapid advances in our understanding of bvFTD, the disease is still under-recognized and commonly misdiagnosed. The result is inappropriate patient care. Recognizing the various presentations of bvFTD and its histological and genetic subtypes might further diagnosis, treatment, and research. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Behavioral and language variants of frontotemporal dementia: a review of key symptoms.

Science.gov (United States)

Laforce, Robert

2013-12-01

While recent advances in the development of neuroimaging and molecular biomarkers for studying neurodegenerative conditions have revolutionized the field, dementia remains a clinical diagnosis. No component of the diagnostic process is more crucial than obtaining a good history. Getting to know the first manifestations of the disease, tracking their evolution and functional impact, combined with a targeted neurological examination, further guides differential diagnosis. This paper summarizes the key symptoms of the behavioral and language variants of frontotemporal dementia. The behavioral variant of frontotemporal dementia (bvFTD) is characterized by severe changes in behavior and personality such as disinhibition, apathy, loss of empathy, or stereotypic behavior, leading to a loss of social competence. Executive functions are impaired, while memory and visuospatial skills are relatively better preserved. By contrast, the language variants or primary progressive aphasias (PPAs) are marked by prominent language disturbances that can be subclassified into a non-fluent/agrammatic variant (naPPA), a semantic variant (svPPA), and a logopenic variant (lvPPA). Although combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis of such heterogeneous conditions, the author emphasizes the importance of accurate recognition of key symptoms that can lead to better identification of underlying neuropathology and appropriate treatment approaches.

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.

Judgments about moral responsibility and determinism in patients with behavioural variant of frontotemporal dementia: still compatibilists.

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Cova, Florian; Bertoux, Maxime; Bourgeois-Gironde, Sacha; Dubois, Bruno

2012-06-01

Do laypeople think that moral responsibility is compatible with determinism? Recently, philosophers and psychologists trying to answer this question have found contradictory results: while some experiments reveal people to have compatibilist intuitions, others suggest that people could in fact be incompatibilist. To account for this contradictory answers, Nichols and Knobe (2007) have advanced a 'performance error model' according to which people are genuine incompatibilist that are sometimes biased to give compatibilist answers by emotional reactions. To test for this hypothesis, we investigated intuitions about determinism and moral responsibility in patients suffering from behavioural frontotemporal dementia. Patients suffering from bvFTD have impoverished emotional reaction. Thus, the 'performance error model' should predict that bvFTD patients will give less compatibilist answers. However, we found that bvFTD patients give answers quite similar to subjects in control group and were mostly compatibilist. Thus, we conclude that the 'performance error model' should be abandoned in favour of other available model that best fit our data. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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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.

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.

Hippocampal sclerosis dementia: an amnesic variant of frontotemporal degeneration

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Onyike, Chiadi U.; Pletnikova, Olga; Sloane, Kelly L.; Sullivan, Campbell; Troncoso, Juan C.; Rabins, Peter V.

2013-01-01

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. PMID:24363834

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

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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.

The Power of Neuroimaging Biomarkers for Screening Frontotemporal Dementia

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McMillan, Corey T.; Avants, Brian B.; Cook, Philip; Ungar, Lyle; Trojanowski, John Q.; Grossman, Murray

2014-01-01

Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative disease that can result from either frontotemporal lobar degeneration (FTLD) or Alzheimer’s disease (AD) pathology. It is critical to establish statistically powerful biomarkers that can achieve substantial cost-savings and increase feasibility of clinical trials. We assessed three broad categories of neuroimaging methods to screen underlying FTLD and AD pathology in a clinical FTD series: global measures (e.g., ventricular volume), anatomical volumes of interest (VOIs) (e.g., hippocampus) using a standard atlas, and data-driven VOIs using Eigenanatomy. We evaluated clinical FTD patients (N=93) with cerebrospinal fluid, gray matter (GM) MRI, and diffusion tensor imaging (DTI) to assess whether they had underlying FTLD or AD pathology. Linear regression was performed to identify the optimal VOIs for each method in a training dataset and then we evaluated classification sensitivity and specificity in an independent test cohort. Power was evaluated by calculating minimum sample sizes (mSS) required in the test classification analyses for each model. The data-driven VOI analysis using a multimodal combination of GM MRI and DTI achieved the greatest classification accuracy (89% SENSITIVE; 89% SPECIFIC) and required a lower minimum sample size (N=26) relative to anatomical VOI and global measures. We conclude that a data-driven VOI approach employing Eigenanatomy provides more accurate classification, benefits from increased statistical power in unseen datasets, and therefore provides a robust method for screening underlying pathology in FTD patients for entry into clinical trials. PMID:24687814

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

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Seelaar, H.; Schelhaas, H.J.; Azmani, A.; Kusters, B.; Rosso, S.; Majoor-Krakauer, D.F.; Rijik, M.C. de; Rizzu, P.; Brummelhuis, M. Ten; Doorn, P.A. van; Kamphorst, W.; Willemsen, R.; Swieten, J. van

2007-01-01

Frontotemporal dementia is accompanied by motor neuron disease (FTD + MND) in approximately 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

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

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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 (John)

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

Dementia in middle-aged patients with schizophrenia.

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Nicolas, Gaël; Beherec, Laurène; Hannequin, Didier; Opolczynski, Gaëlle; Rothärmel, Maud; Wallon, David; Véra, Pierre; Martinaud, Olivier; Guillin, Olivier; Campion, Dominique

2014-01-01

Although numerous studies have assessed cognitive dysfunction in patients with schizophrenia, very few have focused on the diagnosis of dementia. Our objectives were to accurately diagnose dementia in a cohort of middle-aged patients with schizophrenia and to assess the type of dementia. 96 patients with schizophrenia (46 inpatients and 50 outpatients), aged 50 to 70 years, underwent a psychiatric, neurological, and neuropsychological evaluation at baseline and after a 20-month follow-up. We established a 3-step procedure: 1) diagnose dementia according to the DSM-IV criteria, using the Mattis Dementia Rating and Activities of Daily Living scales; 2) characterize dementia using brain imaging, perfusion by 99mTc-ECD-SPECT and laboratory tests including Alzheimer's disease cerebrospinal fluid biomarkers; and 3) search for genetic determinants. Fourteen patients fulfilled the diagnostic criteria of dementia. Four were diagnosed with possible or probable behavioral-variant frontotemporal dementia (bvFTD), two with probable Alzheimer's disease, two with probable vascular dementia (including one due to CADASIL), one with CNS inflammatory disease, and six could not be fully characterized. The diagnosis of dementia in middle-aged patients with schizophrenia is challenging but possible, using a multistep procedure. The most frequent condition, bvFTD, could reflect the presence of an evolutive neurodegenerative process in some patients.

Facial Emotion Recognition Performance Differentiates Between Behavioral Variant Frontotemporal Dementia and Major Depressive Disorder.

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

Misdiagnosis of early behavioral variant frontotemporal dementia (bvFTD) with major depressive disorder (MDD) is not uncommon due to overlapping symptoms. The aim of this study was to improve the discrimination between these disorders using a novel facial emotion perception task. In this prospective cohort study (July 2013-March 2016), we compared 25 patients meeting Rascovsky diagnostic criteria for bvFTD, 20 patients meeting DSM-IV criteria for MDD, 21 patients meeting McKhann diagnostic criteria for Alzheimer's disease dementia, and 31 healthy participants on a novel emotion intensity rating task comprising morphed low-intensity facial stimuli. Participants were asked to rate the intensity of morphed faces on the congruent basic emotion (eg, rating on sadness when sad face is shown) and on the 5 incongruent basic emotions (eg, rating on each of the other basic emotions when sad face is shown). While bvFTD patients underrated congruent emotions (P dementia patients perceived emotions similarly to healthy participants, indicating no impact of cognitive impairment on rating scores. Our congruent and incongruent facial emotion intensity rating task allows a detailed assessment of facial emotion perception in patient populations. By using this simple task, we achieved an almost complete discrimination between bvFTD and MDD, potentially helping improve the diagnostic certainty in early bvFTD. © Copyright 2018 Physicians Postgraduate Press, Inc.

Association of GSK3B With Alzheimer Disease and Frontotemporal Dementia

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Schaffer, Barbara A. J.; Bertram, Lars; Miller, Bruce L.; Mullin, Kristina; Weintraub, Sandra; Johnson, Nancy; Bigio, Eileen H.; Mesulam, Marsel; Wiedau-Pazos, Martina; Jackson, George R.; Cummings, Jeffrey L.; Cantor, Rita M.; Levey, Allan I.; Tanzi, Rudolph E.; Geschwind, Daniel H.

2009-01-01

Background Deposits of abnormally hyperphosphorylated tau are a hallmark of several dementias, including Alzheimer disease (AD), and about 10% of familial frontotemporal dementia (FTD) cases are caused by mutations in the tau gene. As a known tau kinase, GSK3B is a promising candidate gene in the remaining cases of FTD and in AD, for which tau mutations have not been found. Objective To examine the promoter of GSK3B and all 12 exons, including the surrounding intronic sequence, in patients with FTD, patients with AD, and aged healthy subjects to identify single-nucleotide polymorphisms associated with disease. Design, Setting, and Participants Single-nucleotide polymorphism frequency was examined in a case-control cohort of 48 patients with probable AD, 102 patients with FTD, 38 patients with primary progressive aphasia, and 85 aged healthy subjects. Results were followed up in 2 independent AD family samples consisting of 437 multiplex families with AD (National Institute of Mental Health Genetics Initiative AD Study) or 150 sibships discordant for AD (Consortium on Alzheimer’s Genetics Study). Results Several rare sequence variants in GSK3B were identified in the case-control study. An intronic polymorphism (IVS2−68G>A) occurred at more than twice the frequency among patients with FTD (10.8%) and patients with AD (14.6%) than in aged healthy subjects (4.1%). The polymorphism showed association with disease in both follow-up samples independently, although only the Consortium on Alzheimer’s Genetics sample showed the same direction of association as the case-control sample. Conclusions To our knowledge, this is the first evidence that a gene known to be involved in tau phosphorylation, GSK3B, is associated with risk for primary neurodegenerative dementias. This supports previous work in animal models suggesting that such genes are therapeutic targets. PMID:18852354

An investigation of care-based vs. rule-based morality in frontotemporal dementia, Alzheimer's disease, and healthy controls.

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Carr, Andrew R; Paholpak, Pongsatorn; Daianu, Madelaine; Fong, Sylvia S; Mather, Michelle; Jimenez, Elvira E; Thompson, Paul; Mendez, Mario F

2015-11-01

Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer's disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules. Published by Elsevier Ltd.

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

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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.

Mutations in progranulin (GRN) within the spectrum of clinical and pathological phenotypes of frontotemporal dementia

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van Swieten, J.C.; Heutink, P.

2008-01-01

Background: Frontotemporal dementia (FTD) is predominantly a presenile disorder that is characterised by behavioural changes and cognitive impairment, particularly in language and executive functions, and is associated with neurodegeneration in the frontal or temporal cortices, or both. Research

Automatic MRI Quantifying Methods in Behavioral-Variant Frontotemporal Dementia Diagnosis

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Antti Cajanus

2018-02-01

Full Text Available Aims: We assessed the value of automated MRI quantification methods in the differential diagnosis of behavioral-variant frontotemporal dementia (bvFTD from Alzheimer disease (AD, Lewy body dementia (LBD, and subjective memory complaints (SMC. We also examined the role of the C9ORF72-related genetic status in the differentiation sensitivity. Methods: The MRI scans of 50 patients with bvFTD (17 C9ORF72 expansion carriers were analyzed using 6 quantification methods as follows: voxel-based morphometry (VBM, tensor-based morphometry, volumetry (VOL, manifold learning, grading, and white-matter hyperintensities. Each patient was then individually compared to an independent reference group in order to attain diagnostic suggestions. Results: Only VBM and VOL showed utility in correctly identifying bvFTD from our set of data. The overall classification sensitivity of bvFTD with VOL + VBM achieved a total sensitivity of 60%. Using VOL + VBM, 32% were misclassified as having LBD. There was a trend of higher values for classification sensitivity of the C9ORF72 expansion carriers than noncarriers. Conclusion: VOL, VBM, and their combination are effective in differential diagnostics between bvFTD and AD or SMC. However, MRI atrophy profiles for bvFTD and LBD are too similar for a reliable differentiation with the quantification methods tested in this study.

Verb Agreements during On-Line Sentence Processing in Alzheimer's Disease and Frontotemporal Dementia

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Price, C.C.; Grossman, M.

2005-01-01

An on-line ''word detection'' paradigm was used to assess the comprehension of thematic and transitive verb agreements during sentence processing in individuals diagnosed with probable Alzheimer's Disease (AD, n=15) and Frontotemporal Dementia (FTD, n=14). AD, FTD, and control participants (n=17) were asked to listen for a word in a sentence.…

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

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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.

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

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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,

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

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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…

An Investigation of Care-Based vs. Rule-Based Morality in Frontotemporal Dementia, Alzheimer’s Disease, and Healthy Controls

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Carr, Andrew R.; Paholpak, Pongsatorn; Daianu, Madelaine; Fong, Sylvia S.; Mather, Michelle; Jimenez, Elvira E.; Thompson, Paul; Mendez, Mario F.

2015-01-01

Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer’s disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules. PMID:26432341

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

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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

The attribution of animacy and agency in frontotemporal dementia versus Alzheimer's disease.

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Fong, Sylvia S; Paholpak, Pongsatorn; Daianu, Madelaine; Deutsch, Mariel B; Riedel, Brandalyn C; Carr, Andrew R; Jimenez, Elvira E; Mather, Michelle M; Thompson, Paul M; Mendez, Mario F

2017-07-01

Impaired attribution of animacy (state of living or being sentient) and of agency (capability of intrinsically-driven action) may underlie social behavior disturbances in behavioral variant frontotemporal dementia (bvFTD). We presented the Heider and Simmel film of moving geometric shapes to 11 bvFTD patients, 11 Alzheimer's disease (AD) patients, and 12 healthy controls (HCs) and rated their recorded verbal responses for animacy attribution and agency attribution. All participants had skin conductance (SC) continuously recorded while viewing the film, and all dementia participants underwent magnetic resonance imaging (MRI) for regions of interest. The bvFTD patients, but not the AD patients, were impaired in animacy attribution, compared to the HCs. In contrast, both bvFTD and AD groups were impaired in agency attribution, compared to the HCs, and only the HCs had increasing SC responsiveness during viewing of the film. On MRI analysis of cortical thicknesses, animacy scores significantly correlated across groups with the right pars orbitalis and opercularis; agency scores with the left inferior and superior parietal cortices and the supramarginal gyrus; and both scores with the left cingulate isthmus involved in visuospatial context. These findings suggest that bvFTD is specifically associated with impaired animacy attribution from right inferior frontal atrophy. In contrast, both dementias may have impaired agency attribution from left parietal cortical atrophy and absent SC increases during the film, a sympathetic indicator of attribution of a social "story" to the moving shapes. These findings clarify disease-related changes in social attribution and corroborate the neuroanatomical origins of animacy and agency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neurocognitive similarities between severe chronic schizophrenia and behavioural variant frontotemporal dementia.

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Chan, Hui-Minn; Stolwyk, Rene; Neath, Joanna; Kelso, Wendy; Walterfang, Mark; Mocellin, Ramon; Pantelis, Christos; Velakoulis, Dennis

2015-02-28

This study focuses on a group of patients with chronic schizophrenia who have a more severe form of the disorder, as indicated by socio-functional decline, treatment resistance, and recurrent hospitalisation. Previous research has suggested that the pattern and severity of cognitive deficits in people with severe chronic schizophrenia is similar to that observed in behavioural variant frontotemporal dementia (bvFTD). In the current study, we compared neurocognitive performance in 16 cognitive domains in 7 inpatients with severe chronic schizophrenia, 13 community-dwelling outpatients with chronic schizophrenia, 12 patients with bvFTD, and 18 healthy controls. Our findings revealed more similar cognitive profiles between the schizophrenia inpatient and bvFTD groups compared to the schizophrenia outpatient group, who outperformed the former groups. The current results provide preliminary evidence for a distinct schizophrenia subgroup, distinguishable from other chronic schizophrenia patients by poorer clinical and functional status, who have levels of cognitive impairment comparable to those seen in bvFTD patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

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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. © 2013 Elsevier Inc. All rights reserved.

Frontotemporal dementia with trans-activation response DNA-binding protein 43 presenting with catatonic syndrome.

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Watanabe, Ryohei; Kawakami, Ito; Onaya, Mitsumoto; Higashi, Shinji; Arai, Nobutaka; Akiyama, Haruhiko; Hasegawa, Masato; Arai, Tetsuaki

2017-11-07

Catatonia is a clinical syndrome characterized by symptoms such as immobility, mutism, stupor, stereotypy, echophenomena, catalepsy, automatic obedience, posturing, negativism, gegenhalten and ambitendency. This syndrome occurs mostly in mood disorder and schizophrenic patients, and is related to neuronal dysfunction involving the frontal lobe. Some cases of frontotemporal dementia (FTD) with catatonia have been reported, but these cases were not examined by autopsy. Here, we report on a FTD case which showed catatonia after the first episode of brief psychotic disorder. At the age of 58, the patient had a sudden onset of disorganized behavior and meaningless speech. Psychotropic drugs were effective for catatonic symptoms. However, after remission apathy, hyperorality, socially inappropriate behavior, hoarding, and an instinctive grasp reaction appeared and persisted. Brain MRI showed significant atrophy of the bilateral fronto-temporal lobes. A neuropathological examination revealed extensive trans-activation response DNA-binding protein 43 (TDP-43) positive neurocytoplasmic inclusions and dystrophic neurites in the brain, including the cerebral cortex, basal ganglia, and brainstem. Pathological diagnosis was frontotemporal lobar degeneration (FTLD) with TDP-43 (FTLD-TDP) type C, which was also confirmed by the band pattern of C-terminal fragments of TDP-43 on western blotting of sarkosyl-insoluble fractions extracted from the frozen brain. Dysfunction of the thalamus, globus pallidus, supplementary motor area, amygdala and cingulate cortex have been said to be related to the catatonic syndrome. In this case, these areas were affected, showing abnormal TDP-43-positive structures. Further studies are expected to confirm further clinical - pathological correlations to FTLD. © 2017 Japanese Society of Neuropathology.

The frontal-anatomic specificity of design fluency repetitions and their diagnostic relevance for behavioral variant frontotemporal dementia.

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Possin, Katherine L; Chester, Serana K; Laluz, Victor; Bostrom, Alan; Rosen, Howard J; Miller, Bruce L; Kramer, Joel H

2012-09-01

On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).

Augmented Input Reveals Word Deafness in a Man with Frontotemporal Dementia

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Chris Gibbons

2012-01-01

Full Text Available We describe a 57 year old, right handed, English speaking man initially diagnosed with progressive aphasia. Language assessment revealed inconsistent performance in key areas. Expressive language was reduced to a few short, perseverative phrases. Speech was severely apraxic. Primary modes of communication included gesture, pointing, gaze, physical touch and leading. Responses were 100% accurate when he was provided with written words, with random or inaccurate responses for strictly auditory/verbal input. When instructions to subsequent neuropsychological tests were written instead of spoken, performance improved markedly. A comprehensive audiology assessment revealed no hearing impairment. Neuroimaging was unremarkable. Neurobehavioral evaluation utilizing written input led to diagnoses of word deafness and frontotemporal dementia, resulting in very different management. We highlight the need for alternative modes of language input for assessment and treatment of patients with language comprehension symptoms.

Prosocial deficits in behavioral variant frontotemporal dementia relate to reward network atrophy

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Sturm, Virginia E.; Perry, David C.; Wood, Kristie; Hua, Alice Y.; Alcantar, Oscar; Datta, Samir; Rankin, Katherine P.; Rosen, Howard J.; Miller, Bruce L.; Kramer, Joel H.

2017-01-01

Abstract Introduction Empathy and shared feelings of reward motivate individuals to share resources with others when material gain is not at stake. Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disease that affects emotion‐ and reward‐relevant neural systems. Although there is diminished empathy and altered reward processing in bvFTD, how the disease impacts prosocial behavior is less well understood. Methods A total of 74 participants (20 bvFTD, 15 Alzheimer's dis...

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

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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.

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

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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 ...

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

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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.

[Validity of the Spanish version of the Addenbrooke's Cognitive Examination for the diagnosis of dementia and to differentiate Alzheimer's disease and frontotemporal dementia].

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Sarasola, D; de Luján-Calcagno, M; Sabe, L; Crivelli, L; Torralva, T; Roca, M; García-Caballero, A; Manes, F

The Addenbrooke's Cognitive Examination (ACE) is a brief bedside test battery to detect mild dementia and differentiate frontotemporal dementia (FTD) from Alzheimer's disease (AD). To validate the ACE in Spanish. The study evaluated the Spanish version of ACE on 128 subjects consisting in two groups a patient group (n = 76) and a control subjects group (n = 52). The patient group was divided in AD (n = 54) based on the NINCDS-ADRDA criteria and FTD (n = 22) based on the Lund y Manchester criteria. All patients underwent clinical, neuropsychological, radiologic (MRI, CT, and SPECT), and laboratory evaluations. Group's differences were evaluated using ANOVA. The internal consistency of the Spanish version of the ACE was measured using the Cronbach's alpha coefficient. The discriminative capability of the Spanish version of the ACE was examined by the receiver operating characteristic (ROC) analysis. The cut-off score of 86 showed a sensitivity of 92% (CI 95% = 83.6-97.0) and a specificity of 96.2% (CI 95% = 86.8-99.4). The ROC curve showed higher sensitivity and specificity of the ACE than the Mini-Mental State Examination in discriminating the dementia and control group. The VLOM ratio (verbal fluency + language)/(orientation + memory) of 4.87 discriminated for AD. The Spanish version of ACE is a brief and reliable instrument for early detection of dementia in highly educated people and offers a simple objective index to differentiate AD and FTD. More studies in less educated people are warranted.

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

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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.

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

International Nuclear Information System (INIS)

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.

2002-01-01

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

Transcranial magnetic stimulation distinguishes Alzheimer disease from frontotemporal dementia.

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Benussi, Alberto; Di Lorenzo, Francesco; Dell'Era, Valentina; Cosseddu, Maura; Alberici, Antonella; Caratozzolo, Salvatore; Cotelli, Maria Sofia; Micheli, Anna; Rozzini, Luca; Depari, Alessandro; Flammini, Alessandra; Ponzo, Viviana; Martorana, Alessandro; Caltagirone, Carlo; Padovani, Alessandro; Koch, Giacomo; Borroni, Barbara

2017-08-15

To determine whether a transcranial magnetic stimulation (TMS) multiparadigm approach can be used to distinguish Alzheimer disease (AD) from frontotemporal dementia (FTD). Paired-pulse TMS was used to investigate short-interval intracortical inhibition (SICI) and facilitation (ICF), long-interval intracortical inhibition, and short-latency afferent inhibition (SAI) to measure the activity of different intracortical circuits in patients with AD, patients with FTD, and healthy controls (HC). The primary outcome measures were sensitivity and specificity of TMS measures, derived from receiver operating curve analysis. A total of 175 participants met the inclusion criteria. We diagnosed 79 patients with AD, 64 patients with FTD, and 32 HC. We found that while patients with AD are characterized by a specific impairment of SAI, FTD shows a remarkable dysfunction of SICI-ICF intracortical circuits. With the use of the best indexes, TMS differentiated FTD from AD with a sensitivity of 91.8% and specificity of 88.6%, AD from HC with a sensitivity of 84.8% and specificity of 90.6%, and FTD from HC with a sensitivity of 90.2% and specificity of 78.1%. These results were confirmed in patients with mild disease. TMS is a noninvasive procedure that reliably distinguishes AD from FTD and HC and, if these findings are replicated in larger studies, could represent a useful additional diagnostic tool for clinical practice. This study provides Class III evidence that TMS measures can distinguish patients with AD from those with FTD. © 2017 American Academy of Neurology.

HOW TO DIFFERENTIATE FRONTOTEMPORAL FROMALZHEIMER’S DEMENTIA? RECENT DEVELOPMENTS INMOLECULAR GENETICS AND NEUROPATHOLOGY

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Rajko Liščić

2008-05-01

Full Text Available Frontotemporal dementia is a major cause of non-Alzheimer dementia (AD. Frontotemporal lobar degeneration (FTLD is used here as an umbrella term for both clinical andneuropathological entities starting before age of 65 years. FTLD differs clinically from ADbecause memory loss is rarely an early symptom. Instead, the dementia of FTLD is usuallydenoted by behavioral and language difficulties, although clinical and cognitive featuresof FTLD may overlap with AD. Aphasia may be prominent, either fluent or nonfluent.Clinical FTLD is associated with a variety of different neuropathological entities, whichshare common feature of preferential degeneration of the frontal and temporal lobes. Whereas, in the past, most attention focused on FTLD pathology associated with tau-positive inclusions and microtubule associated protein tau gene (MAPT mutations (tauopathies,there has recently been greater attention paid to non-tau, ubiquitin positive inclusions(FTLD-U or non-tauopathies. It is now recognized that FTLD-U is the most common pathology associated with clinical FTLD. Clinically, cases with FTLD-U may additionally presentwith or without motor neuron disease and parkinsonism. Majority of familial cases ofFTLD-U have mutations in the progranulin (PRGN gene. Some families of FTLD-U withPGRN mutation (hereditary dysphasic disinhibition dementia 1 and 2 are characterized,besides behavior and language difficulties, by additional memory loss and AD-type pathology. Recently, the ubiquitinated pathological protein in FTLD-U has been identified asTAR DNA binding protein (TDP 43 and found in an increasing number of neurodegenerative diseases, including AD. The overlap between FTLD-U and AD is important since asmany as 20 % of AD cases show some FTLD-U type TDP-43 pathology. Recent developmentshave helped to clarify the relationship between different types of FTLD and related conditions. Understanding and differentiating between FTLD and AD is very important for

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

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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.

Behavioural-variant frontotemporal dementia: An update

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Olivier Piguet

Full Text Available ABSTRACT Behavioural-variant frontotemporal dementia (bvFTD is characterised by insidious changes in personality and interpersonal conduct that reflect progressive disintegration of the neural circuits involved in social cognition, emotion regulation, motivation and decision making. The underlying pathology is heterogeneous and classified according to the presence of intraneuronal inclusions of tau, TDP-43 or occasionally FUS. Biomarkers to detect these histopathological changes in life are increasingly important with the development of disease-modifying drugs. Gene mutations have been found which collectively account for around 10-20% of cases including a novel hexanucleotide repeat on chromosome 9 (C9orf72. The recently reviewed International Consensus Criteria for bvFTD propose three levels of diagnostic certainly: possible, probable and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process with support from neuropsychological testing designed to detect impairment in decision-making, emotion processing and social cognition. Brain imaging is important for increasing the level of diagnosis certainty. Carer education and support remain of paramount importance.

Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia

NARCIS (Netherlands)

Cuyvers, Elise; Bettens, Karolien; Philtjens, Stephanie; Van Langenhove, Tim; Gijselinck, Ilse; van der Zee, Julie; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; Van Dongen, Jasper; Geerts, Nathalie; Maes, Githa; Mattheijssens, Maria; Peeters, Karin; Cras, Patrick; Vandenberghe, Rik; De Deyn, Peter P.; Van Broeckhoven, Christine; Cruts, Marc; Sleegers, Kristel

Homozygous mutations in exon 2 of TREM2, a gene involved in Nasu-Hakola disease, can cause frontotemporal dementia (FTD). Moreover, a rare TREM2 exon 2 variant (p.R47H) was reported to increase the risk of Alzheimer's disease (AD) with an odds ratio as strong as that for APOE epsilon 4. We

Common and unique gray matter correlates of episodic memory dysfunction in frontotemporal dementia and Alzheimer's disease.

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

2014-04-01

Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel-based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age- and education-matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole-brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each dementia syndrome. Copyright © 2013 Wiley Periodicals, Inc.

Art and the brain: the influence of frontotemporal dementia on an accomplished artist.

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Mell, Joshua Chang; Howard, Sara M; Miller, Bruce L

2003-05-27

A talented artist developed a progressive aphasia syndrome associated with frontotemporal dementia (FTD). As her disease progressed, language and executive skills declined, but her paintings became freer and more original. She demonstrates that artistic development can occur in the setting of language-dominant types of FTD. The study of artistic development in the setting of FTD suggests that language is not required for, and may even inhibit, certain types of visual creativity.

[The neurochemistry and neuropharmacology of frontotemporal dementia].

Science.gov (United States)

Alonso-Navarro, H; Jabbour-Wadih, T; Ayuso-Peralta, L; Jiménez-Jiménez, F J

To review the neurochemical features and therapeutic options for frontotemporal dementia (FTD). The main neurochemical alterations in FTD are the serotoninergic and dopamine depletion. In contrast with Alzheimer's and diffuse Lewy bodies disease, there are not significant alterations of the cholinergic system. Cerebral perfusion and glucose metabolism studies usually show hypoperfusion or hypometabolism, with predominant involvement of temporal and frontal cortices. There have been described some alterations related with oxidative stress and apoptosis, although its pathogenetic role in FTD is not well known. Treatment of FTD is not well established, because there are only a few studies with some drugs. The most studied drugs are serotonin reuptake inhibitors, however, despite the well-known serotoninergic deficiency described in FTD, the results are not conclusive. The main neurochemical alterations of FTD are serotoninergic and dopaminergic deficiencies. The treatment is not well established, although it should be theoretically ideal to use drugs which modulate these neurotransmitter systems.

Functional neuroimaging and presenting psychiatric features in frontotemporal dementia

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Mendez, M F; McMurtray, A; Chen, A K; Shapira, J S; Mishkin, F; Miller, B L

2006-01-01

Background Frontotemporal dementia (FTD) is a behavioural syndrome caused by degeneration of the frontal and anterior temporal lobes. Behavioural disturbances include psychiatric features. Whether patients with FTD present with psychiatric features varies with the initial neuroanatomical variability of FTD. Objective To identify presenting psychiatric changes not part of diagnostic criteria of FTD and contrast them with the degree of hemispheric asymmetry and frontal and temporal hypoperfusion on single photon emission computed tomography (SPECT) imaging. Methods 74 patients who met consensus criteria for FTD were evaluated at a two year follow up. All had brain SPECT on initial presentation. Results of an FTD psychiatric checklist were contrasted with ratings of regional hypoperfusion. Results The regions of predominant hypoperfusion did not correlate with differences on FTD demographic variables but were associated with presenting psychiatric features. Dysthymia and anxiety were associated with right temporal hypoperfusion. “Moria” or frivolous behaviour also occurred with temporal lobe changes, especially on the right. The only significant frontal lobe feature was the presence of a peculiar physical bearing in association with right frontal hypoperfusion. Conclusions Patients with FTD may present with psychiatric changes distinct from the behavioural diagnostic criteria for this disorder. Early temporal involvement is associated with frivolous behaviour and right temporal involvement is associated with emotional disturbances. In contrast, those with right frontal disease may present with alterations in non‐verbal behaviour. PMID:16043457

Behavioral variant frontotemporal dementia: advanced disease stages and death. A step to palliative care.

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Diehl-Schmid, J; Richard-Devantoy, S; Grimmer, T; Förstl, H; Jox, R

2017-08-01

The aim of the present study was to gain insight into the living and care situation in advanced behavioral variant frontotemporal dementia (bvFTD), to describe symptoms and findings in advanced bvFTD, and to evaluate somatic comorbidities and circumstances of death. Standardized interviews were conducted with family caregivers of 83 patients with bvFTD. Forty-four percent of the patients were already deceased at the time of the interview. At the time of the interview or death, respectively, 47% of the patients lived in a nursing home. The median time between symptom onset and nursing home admission was 5.0 ± 5.5 years. In moderate and severe dementia stages almost all patients suffered from severe disabilities including impairment of language, gait, swallowing, and of the ability to care for themselves. Sixteen percent of the patients had got enteral tube feeding. Comorbid somatic diseases were diagnosed in 46% of the patients. Twenty-three percent of the deceased patients had been admitted into a hospital before death. Cardiovascular disease and respiratory disease, mostly pneumonia, were the most frequent causes of death. Advanced bvFTD is characterized by severe cognitive impairment and physical disabilities. BvFTD leads to a premature death. Our findings stress the importance of strategies that maximize patient comfort in advanced disease stages and allow for a peaceful death. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

In vivo amyloid imaging with PET in frontotemporal dementia

International Nuclear Information System (INIS)

Engler, Henry; Santillo, Alexander F.; Lindau, Maria; Lannfelt, Lars; Kilander, Lena; Wang, Shu Xia; Savitcheva, Irina; Nordberg, Agneta; Laangstroem, Bengt

2008-01-01

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.)

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.)

The prevalence of depressive symptoms in frontotemporal dementia: a meta-analysis.

Science.gov (United States)

Chakrabarty, Trisha; Sepehry, Amir A; Jacova, Claudia; Hsiung, Ging-Yuek Robin

2015-01-01

Depression is common in Alzheimer's and vascular dementia and is associated with poorer outcomes; however, less is known about the impact of depression on frontotemporal dementia (FTD). Here, we conducted a meta-analysis of diagnostic methods and the prevalence of depressive symptoms in FTD. PubMed, EMBASE and PsychINFO were queried for 'depression' and/or 'depressive mood' in behavioral- and language-variant FTD. The prevalence and diagnosis of depressive symptoms were extracted from relevant studies and the results pooled using a random-effects model. We included 29 studies in this meta-analysis, with sample sizes ranging from 3 to 73 (n = 870). The omnibus estimated event rate of depressed mood was 0.334 (33%; 95% CI: 0.268-0.407). Symptoms were most commonly assessed via standardized neuropsychiatric rating scales, with other methods including subjective caregiver reports and chart reviews. The study results were heterogeneous due to the variability in diagnostic methods. Depressive symptoms similar to those in other dementias are commonly detected in FTD. However, the diagnostic methods are heterogeneous, and symptoms of depression often overlap with manifestations of FTD. Having a standardized diagnostic approach to depression in FTD will greatly facilitate future research in this area.

Differential regional cerebral glucose metabolism in clinical syndromes of frontotemporal lobar degeneration: a study with FDG PET

International Nuclear Information System (INIS)

Park, J. M.; Cho, S. S.; Na, D. L.; Lee, K. H.; Choi, Y.; Choe, Y. S.; Kim, B. T.; Kim, S. E.

2001-01-01

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

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.

Genetics Home Reference: frontotemporal dementia with parkinsonism-17

Science.gov (United States)

... FTDP-17 . These changes include a loss of inhibition, inappropriate emotional responses, restlessness, neglect of personal hygiene, ... California, San Fransisco Memory and Aging Center Patient Support and Advocacy Resources (4 links) Association for Frontotemporal ...

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...

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.

Dementia and Hospital Readmission Rates: A Systematic Review

Directory of Open Access Journals (Sweden)

Sabrina Pickens

2017-10-01

Full Text Available Background: Although community-dwelling persons with dementia have an increased risk of hospital readmission, no systematic review has examined the contribution of dementia to readmissions. Summary: We examined articles in English, with no restrictions on publication dates, from Medline, PubMed, PsycINFO, CINAHL, and EMBASE. Keywords used were dementia, Alzheimer disease, frontotemporal lobar degeneration, elderly, frontotemporal dementia, executive function, brain atrophy, frontal lobe atrophy, cognitive impairment, readmission, readmit, rehospitalization, patient discharge, and return visit. Of 404 abstracts identified, 77 articles were retrieved; 12 were included. Four of 5 cohort studies showed significantly increased readmission rates in patients with dementia. On average the absolute increase above the comparison groups was from 3 to 13%. Dementia was not associated with readmission in 7 included case-control studies. Key Message: Findings suggest a small increased risk of hospital readmission in individuals with dementia. More study is needed.

Clinical application of positron emission tomography for diagnosis of dementia

International Nuclear Information System (INIS)

Ishii, Kazunari

2002-01-01

Clinical applications of PET studies for dementia are reviewed in this paper. At the mild and moderate stages of Alzheimer's disease (AD), glucose metabolism is reduced not only in the parietotemporal region but also in the posterior cingulate and precuneus. At the advanced stage of AD, there is also a metabolic reduction in the frontal region. In AD patients, glucose metabolism is relatively preserved in the pons, sensorimotor cortices, primary visual cortices, basal ganglia, thalamus and cerebellum. In patients with dementia with Lewy bodies, glucose metabolism in the primary visual cortices is reduced, and this reduction appears to be associated with the reduction pattern in AD patients. In patients with frontotemporal dementia, reduced metabolism in the frontotemporal region is the main feature of this disease, but reduced metabolism in the basal ganglia, and/or parietal metabolic reduction can be associated with the frontotemporal reduction. When corticobasal degeneration is associated with dementia, the reduction pattern of dementia is similar to the reduction pattern in AD and the hallmarks of diagnosing corticobasal degeneration associated with dementia are a reduced metabolism in the primary sensorimotor region and/or basal ganglia and an asymmetric reduction in the two hemispheres. FDG-PET is a very useful tool for the diagnosis of early AD and for the differential diagnosis of dementia. I also describe clinical applications of PET for the diagnosis of dementia in Japan. (author)

Suberoylanilide hydroxamic acid increases progranulin production in iPSC-derived cortical neurons of frontotemporal dementia patients.

Science.gov (United States)

Almeida, Sandra; Gao, Fuying; Coppola, Giovanni; Gao, Fen-Biao

2016-06-01

Mutations in the granulin (GRN) gene cause frontotemporal dementia (FTD) due to progranulin haploinsufficiency. Compounds that can increase progranulin production and secretion may be considered as potential therapeutic drugs; however, very few of them have been directly tested on human cortical neurons. To this end, we differentiated 9 induced pluripotent stem cell lines derived from a control subject, a sporadic FTD case and an FTD patient with progranulin S116X mutation. Treatment with 1 μM suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, increased the production of progranulin in cortical neurons of all subjects at both the mRNA and protein levels without affecting their viability. Microarray analysis revealed that SAHA treatment not only reversed some gene expression changes caused by progranulin haploinsufficiency but also caused massive alterations in the overall transcriptome. Thus, histone deacetylase inhibitors may be considered as therapeutic drugs for GRN mutation carriers. However, this class of drugs also causes drastic changes in overall gene expression in human cortical neurons and their side effects and potential impacts on other pathways should be carefully evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlated patterns of neuropsychological and behavioral symptoms in frontal variant of Alzheimer disease and behavioral variant frontotemporal dementia: a comparative case study.

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Li, Pan; Zhou, Yu-Ying; Lu, Da; Wang, Yan; Zhang, Hui-Hong

2016-05-01

Although the neuropathologic changes and diagnostic criteria for the neurodegenerative disorder Alzheimer's disease (AD) are well-established, the clinical symptoms vary largely. Symptomatically, frontal variant of AD (fv-AD) presents very similarly to behavioral variant frontotemporal dementia (bvFTD), which creates major challenges for differential diagnosis. Here, we report two patients who present with progressive cognitive impairment, early and prominent behavioral features, and significant frontotemporal lobe atrophy on magnetic resonance imaging, consistent with an initial diagnosis of probable bvFTD. However, multimodal functional neuroimaging revealed neuropathological data consistent with a diagnosis of probable AD for one patient (pathology distributed in the frontal lobes) and a diagnosis of probable bvFTD for the other patient (hypometabolism in the bilateral frontal lobes). In addition, the fv-AD patient presented with greater executive impairment and milder behavioral symptoms relative to the bvFTD patient. These cases highlight that recognition of these atypical syndromes using detailed neuropsychological tests, biomarkers, and multimodal neuroimaging will lead to greater accuracy in diagnosis and patient management.

The radiological diagnosis of frontotemporal dementia in everyday practice: an audit of reports, review of diagnostic criteria, and proposal for service improvement

International Nuclear Information System (INIS)

Dewer, B.; Rogers, P.; Ricketts, J.; Mukonoweshuro, W.; Zeman, A.

2016-01-01

Aim: To investigate how commonly valuable diagnostic information regarding the frontotemporal dementias (FTDs) may be missed on routine radiological reporting. Materials and methods: The magnetic resonance imaging (MRI) examination results of a series of 39 consecutive patients in whom the diagnosis was initially thought to be a form of FTD were audited. Twenty-two patients satisfied formal diagnostic criteria for subtypes of FTD. The initial non-specialist radiological reports of the MRI examinations were compared with those of a radiologist who specifically examined the images for the possibility of atypical dementia. Results: Six of the 22 original reports provided a full and accurate description of the radiological findings, while two provided a fully accurate interpretation. Conclusion: Valuable diagnostic information may be missed unless clinicians and radiologists jointly review and discuss brain imaging in cases of dementia. The use of standardised scales may enhance the reporting of MRI examinations for dementia. - Highlights: • Relevant MRI findings in dementia are often omitted from non-specialist reports. • 6/22 reports provided full and accurate description of radiological findings. • 2/22 reports provided full and accurate interpretation. • Multidisciplinary meetings between clinicians and radiologists are valuable. • The use of standardised scales may enhance the reporting of ‘dementia scans’.

Montreal Cognitive Assessment (MoCA): validation study for frontotemporal dementia.

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Freitas, Sandra; Simões, Mário R; Alves, Lara; Duro, Diana; Santana, Isabel

2012-09-01

The Montreal Cognitive Assessment (MoCA) is a brief instrument developed for the screening of milder forms of cognitive impairment, having surpassed the well-known limitations of the Mini-Mental State Examination (MMSE). The aim of the present study was to validate the MoCA as a cognitive screening test for behavioral-variant frontotemporal dementia (bv-FTD) by examining its psychometric properties and diagnostic accuracy. Three matched subgroups of participants were considered: bv-FTD (n = 50), Alzheimer disease (n = 50), and a control group of healthy adults (n = 50). Compared with the MMSE, the MoCA demonstrated consistently superior psychometric properties and discriminant capacity, providing comprehensive information about the patients' cognitive profiles. The diagnostic accuracy of MoCA for bv-FTD was extremely high (area under the curve AUC [MoCA] = 0.934, 95% confidence interval [CI] = 0.866-.974; AUC [MMSE] = 0.772, 95% CI = 0.677-0.850). With a cutoff below 17 points, the MoCA results for sensitivity, specificity, positive predictive value, negative predictive value, and classification accuracy were significantly superior to those of the MMSE. The MoCA is a sensitive and accurate instrument for screening the patients with bv-FTD and represents a better option than the MMSE.

Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration.

Science.gov (United States)

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

2016-01-01

We aimed to evaluate the co-occurrence of language and behavioural impairment in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. 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. 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. 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.

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.)

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

International Nuclear Information System (INIS)

Steketee, Rebecca M.E.; Meijboom, Rozanna; Lugt, Aad van der; Smits, Marion; Bron, Esther E.; Klein, Stefan; Houston, Gavin C.; Mutsaerts, Henri J.M.M.; Mendez Orellana, Carolina P.; Jong, Frank Jan de; Swieten, John C. van

2016-01-01

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.)

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.

C9ORF72 G4C2-repeat expansion and frontotemporal dementia first reported case in Argentina.

Science.gov (United States)

Fernández Suarez, M; Surace, Ezequiel; Harris, P; Tapajoz, F; Sevlever, G; Allegri, R; Russo, G N

2016-06-01

We present a female patient aged 51 who developed behavioral disorders followed by cognitive impairment over 3 years. Neuropsychological, neuropsychiatric, and radiological features suggested a probable behavioral variant of frontotemporal dementia (bvFTD). A family history of amyotrophic lateral sclerosis and parkinsonism suggested the hexanucleotide repeat expansion G4C2 in C9ORF72 . We set up a two-step genotyping algorithm for the detection of the expansion using fragment-length analysis polymerase chain reaction (PCR) and repeat-primed PCR with fluorescent primers. We confirmed the presence of an expanded G4C2 allele in the patient. This represents the first documented case of bvFTD due to a C9ORF72 expansion in Argentina.

Clinical application of positron emission tomography for diagnosis of dementia

Energy Technology Data Exchange (ETDEWEB)

Ishii, Kazunari [Hyogo Brain and Heart Center, Himeji (Japan)

2002-12-01

Clinical applications of PET studies for dementia are reviewed in this paper. At the mild and moderate stages of Alzheimer's disease (AD), glucose metabolism is reduced not only in the parietotemporal region but also in the posterior cingulate and precuneus. At the advanced stage of AD, there is also a metabolic reduction in the frontal region. In AD patients, glucose metabolism is relatively preserved in the pons, sensorimotor cortices, primary visual cortices, basal ganglia, thalamus and cerebellum. In patients with dementia with Lewy bodies, glucose metabolism in the primary visual cortices is reduced, and this reduction appears to be associated with the reduction pattern in AD patients. In patients with frontotemporal dementia, reduced metabolism in the frontotemporal region is the main feature of this disease, but reduced metabolism in the basal ganglia, and/or parietal metabolic reduction can be associated with the frontotemporal reduction. When corticobasal degeneration is associated with dementia, the reduction pattern of dementia is similar to the reduction pattern in AD and the hallmarks of diagnosing corticobasal degeneration associated with dementia are a reduced metabolism in the primary sensorimotor region and/or basal ganglia and an asymmetric reduction in the two hemispheres. FDG-PET is a very useful tool for the diagnosis of early AD and for the differential diagnosis of dementia. I also describe clinical applications of PET for the diagnosis of dementia in Japan. (author)

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 be f...

Dementias show differential physiological responses to salient sounds.

Science.gov (United States)

Fletcher, Phillip D; Nicholas, Jennifer M; Shakespeare, Timothy J; Downey, Laura E; Golden, Hannah L; Agustus, Jennifer L; Clark, Camilla N; Mummery, Catherine J; Schott, Jonathan M; Crutch, Sebastian J; Warren, Jason D

2015-01-01

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 behavioral rating responses to these stimuli were compared in patients fulfilling consensus criteria for dementia syndromes (semantic dementia, n = 10; behavioral variant frontotemporal dementia, n = 16, progressive nonfluent 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 behavioral 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.

[Differentiating early dementia from major depression with the Spanish version of the Addenbrooke's Cognitive Examination].

Science.gov (United States)

Roca, M; Torralva, T; López, P; Marengo, J; Cetkovich, M; Manes, F

In clinical practice it is often difficult to establish whether cognitive impairment is secondary to an affective disorder or a dementing process. To describe the cognitive performance on the Spanish version of the Addenbrooke's Cognitive Examination (ACE) of patients with early dementia and depression. 77 patients with early dementia (53 Alzheimer disease; 24 frontotemporal dementia), 17 patients with major depression and 54 healthy volunteers were tested with the Spanish version of the ACE. Alzheimer disease and frontotemporal dementia groups were significantly lower than the control group and the major depression group. When the major depression group was compared with the control group no significant differences were found. The cognitive performance in the ACE is different in patients with early dementia and patient with depression.

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

Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Anne eHafkemeijer

2015-09-01

Full Text Available Alzheimer’s disease (AD and behavioral variant frontotemporal dementia (bvFTD are the most common types of early-onset dementia. Here, we apply resting state functional magnetic resonance imaging (fMRI to study functional brain connectivity differences between AD and bvFTD.We used resting state fMRI data of 31 AD patients, 25 bvFTD patients, and 29 controls. We studied functional connectivity throughout the entire brain, applying two different analysis techniques, studying network-to-region and region-to-region connectivity. A general linear model approach was used to study group differences, while controlling for physiological noise, age, gender, study center, and regional gray matter volume. Given gray matter differences, we observed decreased network-to-region connectivity in bvFTD between a lateral visual cortical network and lateral occipital and cuneal cortex, and b auditory system network and angular gyrus. In AD, we found decreased network-to-region connectivity between the dorsal visual stream network and lateral occipital and parietal opercular cortex. Region-to-region connectivity was decreased in bvFTD between superior temporal gyrus and cuneal, supracalcarine, intracalcarine cortex, and lingual gyrus. We showed that the pathophysiology of functional brain connectivity is different between AD and bvFTD. However, the group differences in functional connectivity are less abundant than has been shown in previous studies.

MR spectroscopy in dementia

International Nuclear Information System (INIS)

Hauser, T.; Gerigk, L.; Giesel, F.; Schuster, L.; Essig, M.

2010-01-01

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.) [de

Measurement of speech parameters in casual speech of dementia patients

NARCIS (Netherlands)

Roelant Ossewaarde; Roel Jonkers; Fedor Jalvingh; Roelien Bastiaanse

2017-01-01

From the article: "Individuals with dementia often experience a decline in their ability to use language. Language problems have been reported in individuals with dementia caused by Alzheimer’s disease, Parkinson’s disease or degeneration of the fronto-temporal area. Acoustic properties are

Cerebrospinal fluid neurofilament light concentration in motor neuron disease and frontotemporal dementia predicts survival.

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Skillbäck, Tobias; Mattsson, Niklas; Blennow, Kaj; Zetterberg, Henrik

2017-08-01

To aid diagnostics, patient stratification and studies seeking to find treatments for the related diseases motor neuron disease (MND) and frontotemporal dementia (FTD), there is a need to establish a way to assess disease severity and the amount of ongoing neurodegeneration. Previous studies have suggested that cerebrospinal fluid (CSF) neurofilament light (NFL) may serve this purpose. We cross-referenced the Swedish mortality registry with the laboratory database at Sahlgrenska University Hospital to produce a dataset of CSF NFL concentrations and mortality information for 715 MND patients, 87 FTD patients, and 107 healthy controls. Biomarker concentrations were analysed in relation to recorded cause of death and time of death. MND patients had significantly higher CSF NFL concentrations than FTD patients. Both groups had significantly higher concentrations than the healthy controls (mean 709% increase in MND and 307% increase in FTD). Higher concentrations of CSF NFL were associated with shorter survival in both MND and FTD. The results of this study strengthen the notion of CSF NFL as a useful tool for determining disease intensity in MND and FTD patients. Further studies in patient cohorts with clinically subtyped and genetically classified diagnoses are needed.

Definite behavioral variant of frontotemporal dementia with C9ORF72 expansions despite positive Alzheimer's disease cerebrospinal fluid biomarkers.

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Wallon, David; Rovelet-Lecrux, Anne; Deramecourt, Vincent; Pariente, Jeremie; Auriacombe, Sophie; Le Ber, Isabelle; Schraen, Suzanna; Pasquier, Florence; Campion, Dominique; Hannequin, Didier

2012-01-01

Hexanucleotide expansion repeats in the C9ORF72 gene are a major cause of familial and, to a lesser extent, sporadic frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and FTLD-ALS. To examine whether C9ORF72 expansions could be involved in early-onset Alzheimer's disease (EOAD), we genotyped the hexanucleotide repeat region in a large cohort of 114 EOAD patients who all had positive AD cerebrospinal fluid (CSF) biomarkers. We found hexanucleotide expansion repeats of the C9ORF72 gene in 3 out of 114 patients (2.6%). We raise several hypotheses to explain our results and discuss the current status of AD CSF biomarkers in the dementia diagnostic algorithm.

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

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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

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. (c) 2015 APA, all rights reserved).

Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration

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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.

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-like c...

Assessment and Reporting of Driving Fitness in Patients with Dementia in Clinical Practice: Data from SveDem, the Swedish Dementia Registry.

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Lovas, Joel; Fereshtehnejad, Seyed-Mohammad; Cermakova, Pavla; Lundberg, Catarina; Johansson, Björn; Johansson, Kurt; Winblad, Bengt; Eriksdotter, Maria; Religa, Dorota

2016-05-05

Driving constitutes a very important aspect of daily life and is dependent on cognitive functions such as attention, visuo-spatial skills and memory, which are often compromised in dementia. Therefore, the driving fitness of patients with dementia needs to be addressed by physicians and those that are deemed unfit should not be allowed to continue driving. We aimed at investigating to what extent physicians assess driving fitness in dementia patients and determinant factors for revoking of their licenses. This study includes 15113 patients with newly diagnosed dementia and driver's license registered in the Swedish Dementia Registry (SveDem). The main outcomes were reporting to the licensing authority and making an agreement about driving eligibility with the patients. Physicians had not taken any action in 16% of dementia patients, whereas 9% were reported to the authority to have their licenses revoked. Males (OR = 3.04), those with an MMSE score between 20-24 (OR = 1.35) and 10-19 (OR = 1.50), patients with frontotemporal (OR = 3.09) and vascular dementia (OR = 1.26) were more likely to be reported to the authority. For the majority of patients with dementia, driving fitness was assessed. Nevertheless, physicians did not address the issue in a sizeable proportion of dementia patients. Type of dementia, cognitive status, age, sex and burden of comorbidities are independent factors associated with the assessment of driving fitness in patients with dementia. Increased knowledge on how these factors relate to road safety may pave the way for more specific guidelines addressing the issue of driving in patients with dementia.

Pharmacotherapy of dementia

Directory of Open Access Journals (Sweden)

Ajit Avasthi

2016-01-01

Full Text Available This review aims to evaluate the existing evidence for pharmacotherapy for management of dementia. Data search strategies included electronic databases of relevant publications or cross-references. The searches were limited to acetyl cholinesterase inhibitors (AChEIs, memantine, antipsychotics, antidepressants, mood stabilizers, and benzodiazepines. Data in the form of meta-analysis and systemic reviews for treatment in five main types of dementia (Alzheimer′s, frontotemporal, Parkinson′s, Lewy body disease, and vascular type were extracted. If a meta-analysis or systemic review was not available, then the searches included evaluation of data in the form of double-blind, randomized controlled trials or open-label studies. Various studies suggest that compared to placebo, AChEIs and memantine are associated with better outcome in all domains of Alzheimer′s disease. In addition, combination therapy of AChEIs and memantine is superior to monotherapy with AChEIs in terms of behavioral disturbances, activities of daily living, and global assessment. In patients with dementia associated with Parkinson′s disease or Lewy body dementia, use of donepezil, rivastigmine, and memantine is associated with significant efficacy on the global outcome measures when compared with placebo. Compared to placebo, AChEIs, but not memantine, have also been shown to have better cognitive outcomes in patients with dementia associated with Parkinson′s disease or Lewy body dementia. Data are limited for the role of pharmacotherapy in management of frontotemporal dementia. In patients of vascular dementia, all AChEIs and memantine show some beneficial effects on cognition. Antidepressants and antipsychotics have been shown to be beneficial in management of behavioral symptoms and agitation. However, it is important to remember that there is black box warning for use of antipsychotics among patients with dementia. One of the major limitations of the research is

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.

Dementias show differential physiological responses to salient sounds

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Fletcher, Phillip D.; Nicholas, Jennifer M.; Shakespeare, Timothy J.; Downey, Laura E.; Golden, Hannah L.; Agustus, Jennifer L.; Clark, Camilla N.; Mummery, Catherine J.; Schott, Jonathan M.; Crutch, Sebastian J.; Warren, Jason D.

2015-01-01

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 behavioral rating responses to these stimuli were compared in patients fulfilling consensus criteria for dementia syndromes (semantic dementia, n = 10; behavioral variant frontotemporal dementia, n = 16, progressive nonfluent 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 behavioral 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. PMID:25859194

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

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Almeida, Sandra; Zhang, Zhijun; Coppola, Giovanni; Mao, Wenjie; Futai, Kensuke; Karydas, Anna; Geschwind, Michael D.; Tartaglia, M. Carmela; Gao, Fuying; Gianni, Davide; Sena-Esteves, Miguel; Geschwind, Daniel H.; Miller, Bruce L.; Farese, Robert V.; Gao, Fen-Biao

2012-01-01

SUMMARY The pathogenic mechanisms of frontotemporal dementia (FTD) remain poorly understood. Here we generated multiple induced pluripotent stem cell (iPSC) lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel GRN mutation (PGRN S116X). In neurons and microglia differentiated from PGRN S116X iPSCs, the levels of intracellular and secreted progranulin were reduced, establishing patient-specific cellular models of progranulin 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 PI3K and MAPK pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by progranulin expression. Our findings identify cell-autonomous, reversible defects in patient neurons with progranulin deficiency and provide a new model for studying progranulin-dependent pathogenic mechanisms and testing potential therapies. PMID:23063362

Diagnosing, monitoring and managing behavioural variant frontotemporal dementia.

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Piguet, Olivier; Kumfor, Fiona; Hodges, John

2017-09-02

Behavioural variant frontotemporal dementia is characterised by insidious changes in personality and interpersonal conduct that reflect progressive disintegration of the neural circuits involved in social cognition, emotion regulation, motivation and decision making. The underlying pathology is heterogeneous and classified according to the presence of intraneuronal inclusions of tau, TDP-43 or, occasionally, fused in sarcoma proteins. Biomarkers to detect these histopathological changes in life are increasingly important with the development of disease-modifying drugs. A number of gene abnormalities have been identified, the most common being an expansion in the C9orf72 gene, which together account for most familial cases. The 2011 international consensus criteria propose three levels of diagnostic certainty: possible, probable and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process, with support from neuropsychological testing designed to detect impairment in decision making, emotion processing and social cognition. Brain imaging is important for increasing the level of diagnosis certainty over time. Carer education and support remain of paramount importance.

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.

Meta-analytic Review of Memory Impairment in Behavioral Variant Frontotemporal Dementia.

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Poos, Jackie M; Jiskoot, Lize C; Papma, Janne M; van Swieten, John C; van den Berg, Esther

2018-03-19

A meta-analysis of the extent, nature and pattern of memory performance in behavioral variant frontotemporal dementia (bvFTD). Multiple observational studies have challenged the relative sparing of memory in bvFTD as stated in the current diagnostic criteria. We performed a meta-analytic review covering the period 1967 to February 2017 of case-control studies on episodic memory in bvFTD versus control participants (16 studies, 383 patients, 603 control participants), and patients with bvFTD versus those with Alzheimer's disease (AD) (20 studies, 452 bvFTD, 874 AD). Differences between both verbal and non-verbal working memory, episodic memory learning and recall, and recognition memory were examined. Data were extracted from the papers and combined into a common metric measure of effect, Hedges' d. Patients with bvFTD show large deficits in memory performance compared to controls (Hedges' d -1.10; 95% confidence interval [CI] [-1.23, -0.95]), but perform significantly better than patients with AD (Hedges' d 0.85; 95% CI [0.69, 1.03]). Learning and recall tests differentiate best between patients with bvFTD and AD (p<.01). There is 37-62% overlap in test scores between the two groups. This study points to memory disorders in patients with bvFTD, with performance at an intermediate level between controls and patients with AD. This indicates that, instead of being an exclusion criterion for bvFTD diagnosis, memory deficits should be regarded as a potential integral part of the clinical spectrum. (JINS, 2018, 24, 1-13).

A Novel MAPT Mutation, G55R, in a Frontotemporal Dementia Patient Leads to Altered Tau Function

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Guzman, Elmer; Barczak, Anna; Chodakowska-Żebrowska, Małgorzata; Barcikowska, Maria; Feinstein, Stuart

2013-01-01

Over two dozen mutations in the gene encoding the microtubule associated protein tau cause a variety of neurodegenerative dementias known as tauopathies, including frontotemporal dementia (FTD), PSP, CBD and Pick's disease. The vast majority of these mutations map to the C-terminal region of tau possessing microtubule assembly and microtubule dynamics regulatory activities as well as the ability to promote pathological tau aggregation. Here, we describe a novel and non-conservative tau mutation (G55R) mapping to an alternatively spliced exon encoding part of the N-terminal region of the protein in a patient with the behavioral variant of FTD. Although less well understood than the C-terminal region of tau, the N-terminal region can influence both MT mediated effects as well as tau aggregation. The mutation changes an uncharged glycine to a basic arginine in the midst of a highly conserved and very acidic region. In vitro, 4-repeat G55R tau nucleates microtubule assembly more effectively than wild-type 4-repeat tau; surprisingly, this effect is tau isoform specific and is not observed in a 3-repeat G55R tau versus 3-repeat wild-type tau comparison. In contrast, the G55R mutation has no effect upon the abilities of tau to regulate MT growing and shortening dynamics or to aggregate. Additionally, the mutation has no effect upon kinesin translocation in a microtubule gliding assay. Together, (i) we have identified a novel tau mutation mapping to a mutation deficient region of the protein in a bvFTD patient, and (ii) the G55R mutation affects the ability of tau to nucleate microtubule assembly in vitro in a 4-repeat tau isoform specific manner. This altered capability could markedly affect in vivo microtubule function and neuronal cell biology. We consider G55R to be a candidate mutation for bvFTD since additional criteria required to establish causality are not yet available for assessment. PMID:24086739

Strategic value-directed learning and memory in Alzheimer's disease and behavioural-variant frontotemporal dementia.

Science.gov (United States)

Wong, Stephanie; Irish, Muireann; Savage, Greg; Hodges, John R; Piguet, Olivier; Hornberger, Michael

2018-02-12

In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants' memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory. © 2018 The British Psychological Society.

Head to head comparison of [18F] AV-1451 and [18F] THK5351 for tau imaging in Alzheimer's disease and frontotemporal dementia

International Nuclear Information System (INIS)

Jang, Young Kyoung; Kim, Hee Jin; Jang, Hyemin; Lyoo, Chul Hyoung; Cho, Hanna; Park, Seongbeom; Oh, Seung Jun; Oh, Minyoung; Kim, Jae Seung; Ryu, Young Hoon; Choi, Jae Yong; Rabinovici, Gil D.; Moon, Seung Hwan; Lee, Jin San; Jagust, William J.; Na, Duk L.; Seo, Sang Won

2018-01-01

Tau accumulation is a core pathologic change in various neurodegenerative diseases including Alzheimer's disease and frontotemporal lobar degeneration-tau. Recently, tau positron emission tomography tracers such as [ 18 F] AV-1451 and [ 18 F] THK5351 have been developed to detect tau deposition in vivo. In the present study, we performed a head to head comparison of these two tracers in Alzheimer's disease and frontotemporal dementia cases and aimed to investigate which tracers are better suited to image tau in these disorders. A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We recruited eight participants (two Alzheimer's disease, four frontotemporal dementia and two normal controls) who underwent magnetic resonance image, amyloid positron emission tomography with [ 18 F]-Florbetaben and tau positron emission tomography with both THK5351 and AV-1451. To measure regional AV1451 and THK5351 uptakes, we used the standardized uptake value ratios by dividing mean activity in target volume of interest by mean activity in the cerebellar hemispheric gray matter. Although THK5351 and AV-1451 uptakes were highly correlated, cortical uptake of AV-1451 was more striking in Alzheimer's disease, while cortical uptake of THK5351 was more prominent in frontotemporal dementia. THK5351 showed higher off-target binding than AV-1451 in the white matter, midbrain, thalamus, and basal ganglia. AV-1451 is more sensitive and specific to Alzheimer's disease type tau and shows lower off-target binding, while THK5351 may mirror non-specific neurodegeneration. (orig.)

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 (Cornelia); 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

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

NARCIS (Netherlands)

Sleegers, K.; Roks, G.; Theuns, J.; Aulchenko, Y. S.; Rademakers, R.; Cruts, M.; van Gool, W. A.; van Broeckhoven, C.; Heutink, P.; Oostra, B. A.; van Swieten, J. C.; van Duijn, C. M.

2004-01-01

Despite 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 1750. The

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 violence compared with 2% of patients with AD (P = .003). Common manifestations of criminal behavior in the bvFTD group included theft, traffic violations, sexual 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

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.)

Functional connectivity and microstructural white matter changes in phenocopy frontotemporal dementia

International Nuclear Information System (INIS)

Meijboom, R.; Steketee, R.M.E.; Lugt, A. van der; Smits, M.; Koning, I. de; Osse, R.J.; Jiskoot, L.C.; Jong, F.J. de; Swieten, J.C. van

2017-01-01

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.)

Meta-Analysis of Facial Emotion Recognition in Behavioral Variant Frontotemporal Dementia: Comparison With Alzheimer Disease and Healthy Controls.

Science.gov (United States)

Bora, Emre; Velakoulis, Dennis; Walterfang, Mark

2016-07-01

Behavioral disturbances and lack of empathy are distinctive clinical features of behavioral variant frontotemporal dementia (bvFTD) in comparison to Alzheimer disease (AD). The aim of this meta-analytic review was to compare facial emotion recognition performances of bvFTD with healthy controls and AD. The current meta-analysis included a total of 19 studies and involved comparisons of 288 individuals with bvFTD and 329 healthy controls and 162 bvFTD and 147 patients with AD. Facial emotion recognition was significantly impaired in bvFTD in comparison to the healthy controls (d = 1.81) and AD (d = 1.23). In bvFTD, recognition of negative emotions, especially anger (d = 1.48) and disgust (d = 1.41), were severely impaired. Emotion recognition was significantly impaired in bvFTD in comparison to AD in all emotions other than happiness. Impairment of emotion recognition is a relatively specific feature of bvFTD. Routine assessment of social-cognitive abilities including emotion recognition can be helpful in better differentiating between cortical dementias such as bvFTD and AD. © The Author(s) 2016.

Difficulties in detecting behavioral symptoms of frontotemporal lobar degeneration across cultures.

Science.gov (United States)

Papatriantafyllou, John D; Viskontas, Indre V; Papageorgiou, Sokratis G; Miller, Bruce L; Pavlic, Danijela; Bingol, Ayse; Yener, Gorsev

2009-01-01

Cross-cultural studies of neurodegenerative disorders are especially important when the disease in question is difficult to diagnose, particularly if symptoms of the illness include behavioral disturbances that may be interpreted differently in different cultures. One such disease is frontotemporal lobar degeneration (FTLD), an early-age-of-onset dementia that disproportionately affects social behavior. We report the demographic and neuropsychologic characteristics of more than 300 patients diagnosed with FTLD in the United States, Greece, and Turkey. We find that patients with the frontal variant of frontotemporal dementia (FTD) are diagnosed at an earlier age and report earlier symptom onset in the United States than in Greece or Turkey. Furthermore, neuropsychologic measures indicate that at diagnosis, FTD patients in the United States are less impaired than patients in Greece and Turkey. Patients with FTD in Greece and Turkey are diagnosed later in the disease, presumably because their behavioral symptoms are not easily detected by the medical system in these countries. Our study underscores the need to create culturally appropriate indices of the behavioral symptoms of FTLD, so that patients may be diagnosed and treated at an earlier stage.

Lost and forgotten? Orientation versus memory in Alzheimer's disease and frontotemporal dementia.

Science.gov (United States)

Yew, Belinda; Alladi, Suvarna; Shailaja, Mekala; Hodges, John R; Hornberger, Michael

2013-01-01

Recent studies suggest that significant memory problems are not specific to Alzheimer's disease (AD) but can be also observed in other neurodegenerative conditions, such as behavioral variant frontotemporal dementia (bvFTD). We investigated whether orientation (spatial & temporal) information is a better diagnostic marker for AD compared to memory and whether their atrophy correlates of orientation and memory differ. A large sample (n = 190) of AD patients (n = 73), bvFTD patients (n = 54), and healthy controls (n = 63) underwent testing. A subset of the patients (n = 72) underwent structural imaging using voxel-based morphometry analysis of magnetic resonance brain imaging. Orientation and memory scores from the Addenbrooke's Cognitive Examination showed that AD patients had impaired orientation and memory, while bvFTD patients performing at control level for orientation but had impaired memory. A logistic regression showed that 78% of patients could be classified on the basis of orientation and memory scores alone at clinic presentation. Voxel-based morphometry analysis was conducted using orientation and memory scores as covariates, which showed that the neural correlates for orientation and memory also dissociated with posterior hippocampus cortex being related to orientation in AD, while the anterior hippocampus was associated with memory performance in the AD and bvFTD patients. Orientation and memory measures discriminate AD and bvFTD to a high degree and tap into different hippocampal regions. Disorientation and posterior hippocampus appears therefore specific to AD and will allow clinicians to discriminate AD patients from other neurodegenerative conditions with similar memory deficits at clinic presentation.

Motor speech signature of behavioral variant frontotemporal dementia: Refining the phenotype.

Science.gov (United States)

Vogel, Adam P; Poole, Matthew L; Pemberton, Hugh; Caverlé, Marja W J; Boonstra, Frederique M C; Low, Essie; Darby, David; Brodtmann, Amy

2017-08-22

To provide a comprehensive description of motor speech function in behavioral variant frontotemporal dementia (bvFTD). Forty-eight individuals (24 bvFTD and 24 age- and sex-matched healthy controls) provided speech samples. These varied in complexity and thus cognitive demand. Their language was assessed using the Progressive Aphasia Language Scale and verbal fluency tasks. Speech was analyzed perceptually to describe the nature of deficits and acoustically to quantify differences between patients with bvFTD and healthy controls. Cortical thickness and subcortical volume derived from MRI scans were correlated with speech outcomes in patients with bvFTD. Speech of affected individuals was significantly different from that of healthy controls. The speech signature of patients with bvFTD is characterized by a reduced rate (75%) and accuracy (65%) on alternating syllable production tasks, and prosodic deficits including reduced speech rate (45%), prolonged intervals (54%), and use of short phrases (41%). Groups differed on acoustic measures derived from the reading, unprepared monologue, and diadochokinetic tasks but not the days of the week or sustained vowel tasks. Variability of silence length was associated with cortical thickness of the inferior frontal gyrus and insula and speech rate with the precentral gyrus. One in 8 patients presented with moderate speech timing deficits with a further two-thirds rated as mild or subclinical. Subtle but measurable deficits in prosody are common in bvFTD and should be considered during disease management. Language function correlated with speech timing measures derived from the unprepared monologue only. © 2017 American Academy of Neurology.

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.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.)

Imaging dementias

International Nuclear Information System (INIS)

Savoiardo, M.; Grisoli, M.

2001-01-01

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.)

Head to head comparison of [{sup 18}F] AV-1451 and [{sup 18}F] THK5351 for tau imaging in Alzheimer's disease and frontotemporal dementia

Energy Technology Data Exchange (ETDEWEB)

Jang, Young Kyoung; Kim, Hee Jin; Jang, Hyemin [Sungkyunkwan University School of Medicine, Department of Neurology, Samsung Medical Center, Seoul (Korea, Republic of); Neuroscience Center, Samsung Medical Center, Seoul (Korea, Republic of); Lyoo, Chul Hyoung; Cho, Hanna [Yonsei University College of Medicine, Department of Neurology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Park, Seongbeom [Sungkyunkwan University School of Medicine, Department of Neurology, Samsung Medical Center, Seoul (Korea, Republic of); Oh, Seung Jun; Oh, Minyoung; Kim, Jae Seung [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ryu, Young Hoon; Choi, Jae Yong [Yonsei University College of Medicine, Department of Nuclear Medicine, Gangnam Severance Hospital, Seoul (Korea, Republic of); Rabinovici, Gil D. [University of California, San Francisco, Memory and Aging Center, San Francisco, CA (United States); University of California, Berkeley, Helen Wills Neuroscience Institute, Berkeley, CA (United States); Moon, Seung Hwan [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Jin San [Kyung Hee University Hospital, Department of Neurology, Seoul (Korea, Republic of); Jagust, William J. [University of California, Berkeley, Helen Wills Neuroscience Institute, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Center of Functional Imaging, Berkeley, CA (United States); Na, Duk L. [Sungkyunkwan University School of Medicine, Department of Neurology, Samsung Medical Center, Seoul (Korea, Republic of); Neuroscience Center, Samsung Medical Center, Seoul (Korea, Republic of); Sungkyunkwan University, Department of Health Sciences and Technology, SAIHST, Seoul (Korea, Republic of); Seo, Sang Won [Sungkyunkwan University School of Medicine, Department of Neurology, Samsung Medical Center, Seoul (Korea, Republic of); Neuroscience Center, Samsung Medical Center, Seoul (Korea, Republic of); Sungkyunkwan University, Department of Health Sciences and Technology, SAIHST, Seoul (Korea, Republic of); Sungkyunkwan University, Department of Clinical Research Design and Evaluation, SAIHST, Seoul (Korea, Republic of)

2018-03-15

Tau accumulation is a core pathologic change in various neurodegenerative diseases including Alzheimer's disease and frontotemporal lobar degeneration-tau. Recently, tau positron emission tomography tracers such as [{sup 18}F] AV-1451 and [{sup 18}F] THK5351 have been developed to detect tau deposition in vivo. In the present study, we performed a head to head comparison of these two tracers in Alzheimer's disease and frontotemporal dementia cases and aimed to investigate which tracers are better suited to image tau in these disorders. A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We recruited eight participants (two Alzheimer's disease, four frontotemporal dementia and two normal controls) who underwent magnetic resonance image, amyloid positron emission tomography with [{sup 18}F]-Florbetaben and tau positron emission tomography with both THK5351 and AV-1451. To measure regional AV1451 and THK5351 uptakes, we used the standardized uptake value ratios by dividing mean activity in target volume of interest by mean activity in the cerebellar hemispheric gray matter. Although THK5351 and AV-1451 uptakes were highly correlated, cortical uptake of AV-1451 was more striking in Alzheimer's disease, while cortical uptake of THK5351 was more prominent in frontotemporal dementia. THK5351 showed higher off-target binding than AV-1451 in the white matter, midbrain, thalamus, and basal ganglia. AV-1451 is more sensitive and specific to Alzheimer's disease type tau and shows lower off-target binding, while THK5351 may mirror non-specific neurodegeneration. (orig.)

Problems of Face Recognition in Patients with Behavioral Variant Frontotemporal Dementia

OpenAIRE

Chandra, Sadanandavalli Retnaswami; Patwardhan, Ketaki; Pai, Anupama Ramakanth

2017-01-01

Introduction: Faces are very special as they are most essential for social cognition in humans. It is partly understood that face processing in its abstractness involves several extra striate areas. One of the most important causes for caregiver suffering in patients with anterior dementia is lack of empathy. This apart from being a behavioral disorder could be also due to failure to categorize the emotions of the people around them. Patients and Methods: Inlusion criteria: DSM IV for Bv FTD ...

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.

CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients.

Science.gov (United States)

Skillbäck, Tobias; Delsing, Louise; Synnergren, Jane; Mattsson, Niklas; Janelidze, Shorena; Nägga, Katarina; Kilander, Lena; Hicks, Ryan; Wimo, Anders; Winblad, Bengt; Hansson, Oskar; Blennow, Kaj; Eriksdotter, Maria; Zetterberg, Henrik

2017-11-01

A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271). We compared CSF/serum albumin ratio to 2 healthy control groups (n = 292, n = 20), between dementia diagnoses, and tested biomarker associations. Patients in DLB, LAD, VaD, MIX, other, and NOS groups had higher CSF/serum albumin ratio than controls. CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers. Our data show that BBB leakage is common in dementias. The lack of association between CSF/serum albumin ratio and AD biomarkers suggests that BBB dysfunction is not inherent to AD but might represent concomitant cerebrovascular pathology. Copyright © 2017 Elsevier Inc. All rights reserved.

Dementia: role of MRI

International Nuclear Information System (INIS)

Georgieva-Kozarova, G.

2012-01-01

Full text: This presentation will focus on the role of MRI in the diagnosis of dementia and related diseases. We will discuss the following subjects: 1. Systematic assessment of MR in dementia 2. MR protocol for dementia 3. Typical findings in the most common dementia syndrome Alzheimer's disease (AD), Vascular Dementia (VaD), Frontotemporal lobe dementia (FTLD) 4. Short overview of neurodegenerative disorders which may be associated with dementia. The role of neuroimaging in dementia nowadays extends to support the diagnosis of specific neurodegenerative disorders. It is a challenge to the early diagnosis of neurodegenerative diseases such as Alzheimer's disease. Early diagnosis includes recognition of predementia conditions, such as mild cognitive impairment (MCI). Neuroimaging may also be used to assess disease progression and is adopted in current trials investigating MCI and AD. An MR-study of a patient suspected of having dementia must be assessed in a standardized way. First of all, treatable diseases like subdural hematomas, tumors and hydrocephalus need to be excluded. Next we should look for signs of specific dementias such as: Alzheimer's disease (AD): medial temporal lobe atrophy (MTA) and parietal atrophy. Frontotemporal Lobar Degeneration (FTLD): (asymmetric) frontal lobe atrophy and atrophy of the temporal pole. Vascular Dementia (VaD): global atrophy, diffuse white matter lesions, lacunas and 'strategic infarcts' (infarcts in regions that are involved in cognitive function). Dementia with Lewy bodies (DLB): in contrast to other forms of dementia usually no specific abnormalities. So when we study the MR images we should score in a systematic way for global atrophy, focal atrophy and for vascular disease (i.e. infarcts, white matter lesions, lacunas)

Tower of London test: a comparison between conventional statistic approach and modelling based on artificial neural network in differentiating fronto-temporal dementia from Alzheimer's disease.

Science.gov (United States)

Franceschi, Massimo; Caffarra, Paolo; Savarè, Rita; Cerutti, Renata; Grossi, Enzo

2011-01-01

The early differentiation of Alzheimer's disease (AD) from frontotemporal dementia (FTD) may be difficult. The Tower of London (ToL), thought to assess executive functions such as planning and visuo-spatial working memory, could help in this purpose. Twentytwo Dementia Centers consecutively recruited patients with early FTD or AD. ToL performances of these groups were analyzed using both the conventional statistical approaches and the Artificial Neural Networks (ANNs) modelling. Ninety-four non aphasic FTD and 160 AD patients were recruited. ToL Accuracy Score (AS) significantly (p advanced ANNs developed by Semeion Institute. The best ANNs were selected and submitted to ROC curves. The non-linear model was able to discriminate FTD from AD with an average AUC for 7 independent trials of 0.82. The use of hidden information contained in the different items of ToL and the non linear processing of the data through ANNs allows a high discrimination between FTD and AD in individual patients.

Progranulin, a Glycoprotein Deficient in Frontotemporal Dementia, Is a Novel Substrate of Several Protein Disulfide Isomerase Family Proteins

OpenAIRE

Almeida, Sandra; Zhou, Lijuan; Gao, Fen-Biao

2011-01-01

The reduced production or activity of the cysteine-rich glycoprotein progranulin is responsible for about 20% of cases of familial frontotemporal dementia. However, little is known about the molecular mechanisms that govern the level and secretion of progranulin. Here we show that progranulin is expressed in mouse cortical neurons and more prominently in mouse microglia in culture and is abundant in the endoplasmic reticulum (ER) and Golgi. Using chemical crosslinking, immunoprecipitation, an...

Neuroimaging Correlates of Frontotemporal Dementia Associated with SQSTM1 Mutations.

Science.gov (United States)

Luis, Elkin; Ortiz, Alexandra; Eudave, Luis; Ortega-Cubero, Sara; Borroni, Barbara; van der Zee, Julie; Gazzina, Stefano; Caroppo, Paola; Rubino, Elisa; D'Agata, Federico; Le Ber, Isabelle; Santana, Isabel; Cunha, Gil; Almeida, Maria R; Boutoleau-Bretonnière, Claire; Hannequin, Didier; Wallon, David; Rainero, Innocenzo; Galimberti, Daniela; Van Broeckhoven, Christine; Pastor, Maria A; Pastor, Pau

2016-05-07

Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD). The aim of the study was to determine whether a characteristic pattern of grey and white matter loss is associated with SQSTM1 dysfunction. We performed a voxel-based morphometry (VBM) study in FTD subjects carrying SQSTM1 pathogenic variants (FTD/SQSTM1 mutation carriers; n = 10), compared with FTD subjects not carrying SQSTM1 mutations (Sporadic FTD; n = 20) and healthy controls with no SQSTM1 mutations (HC/SQSTM1 noncarriers; n = 20). The groups were matched according to current age, disease duration, and gender. After comparing FTD/SQSTM1 carriers with Sporadic FTD, a predominantly right cortical atrophy pattern was localized in the inferior frontal, medial orbitofrontal, precentral gyri, and the anterior insula. White matter atrophy was found in both medial and inferior frontal gyri, pallidum, and putamen. FTD/SQSTM1 carriers compared with HC/SQSTM1 noncarriers showed atrophy at frontal, temporal, and parietal lobes of both hemispheres whereas the MRI pattern found in Sporadic FTD compared with controls was frontal and left temporal lobe atrophy, extending toward parietal and occipital lobes of both hemispheres. These results suggest that fronto-orbito-insular regions including corticospinal projections as described in ALS are probably more susceptible to the damaging effect of SQSTM1 mutations delineatinga specific gene-linked atrophy pattern.

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

Music recognition in frontotemporal lobar degeneration and Alzheimer disease.

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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.

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

2013-01-01

Objective 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. Background Recognition of familiar music depends on several levels of processing. There are few studies about how patients with dementia recognize familiar music. Methods Subjects were administered tasks that assess pitch and melody discrimination, detection of pitch errors in familiar melodies, and naming of familiar melodies. Results 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 MRI 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. Conclusions 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. PMID:21617528

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.

Is postoperative cognitive dysfunction a risk factor for dementia?

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Steinmetz, J; Siersma, Volkert Dirk; Kessing, L V

2013-01-01

BACKGROUND: /st>Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients after major surgery. An association between POCD and the development of dementia has been suspected. In this study, we assessed if POCD was a risk factor for the occurrence of dementia. METHODS...... surgery, using a neuropsychological test battery. The time of (first) occurrence of dementia after surgery was assessed using the National Patient Register and the Psychiatric Central Research Register. Recorded dementia diagnoses (ICD-8 and ICD-10) were: Alzheimer's disease, vascular dementia......, frontotemporal dementia, or dementia without specification. The risk of dementia according to POCD was assessed in the Cox regression models. RESULTS: /st>A total of 686 patients with a median age of 67 [inter-quartile range (IQR) 61-74] yr were followed for a median of 11.1 (IQR 5.2-12.6) yr. Only 32 patients...

C9orf72 and UNC13A Are Shared Risk Loci for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: A Genome-Wide Meta-Analysis

NARCIS (Netherlands)

Diekstra, F.P.; Van Deerlin, V.M.; van Swieten, J.C.; Al-Chalabi, A.; Ludolph, A.C.; Weishaupt, J.H.; Hardiman, O.; Landers, J.E.; Brown, R.H.; Es, M.A.; Pasterkamp, R.J.; Koppers, M.; Andersen, P.M.; Estrada, K.; Rivadeneira, F.; Hofman, A.; Uitterlinden, A. G.; Van Damme, P.; Melki, J.; Meininger, V.; Shatunov, A.; Shaw, C.E.; Leigh, P.N.; Shaw, P.J.; Morrison, K.E.; Fogh, I.; Chio, A.; Traynor, B.J.; Czell, D.; Weber, M.; Heutink, P.; Bakker, P.I.W.; Silani, V.; Robberecht, W.; Van den Berg, L.H.; Veldink, J.H.

2014-01-01

Objective Substantial clinical, pathological, and genetic overlap exists between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 inclusions have been found in both ALS and FTD cases (FTD-TDP). Recently, a repeat expansion in C9orf72 was identified as the causal variant

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.

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

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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.

miRNA expression profiles in cerebrospinal fluid and blood of patients with Alzheimer's disease and other types of dementia - an exploratory study

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Sørensen, Sofie Sølvsten; Hillig, Ann-Britt Nygaard; Christensen, Thomas

2016-01-01

. 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...... significantly up-regulated and miR-194-5p was significantly down-regulated in AD patients compared to controls. CONCLUSIONS: Detection of miRNA expression profiles in blood and in particular CSF of patients diagnosed with different types of dementia is feasible and it seems that several expressional differences...

Anatomical Correlates of Non-Verbal Perception in Dementia Patients

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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.

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

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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.

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.

[False recognition of faces associated with fronto-temporal dementia with prosopagnosia].

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Verstichel, P

2005-09-01

The association of prosopagnosia and false recognition of faces is unusual and contributes to our understanding of the generation of facial familiarity. A 67-year-old man with a left prefrontal traumatic lesion, developed a temporal variety of fronto-temporal dementia (semantic dementia) with amyotrophic lateral sclerosis. Cerebral imagery demonstrated a bilateral, temporal anterior atrophy predominating in the right hemisphere. The main cognitive signs consisted in severe difficulties to recognize faces of familiar people (prosopagnosia), associated with systematic false recognition of unfamiliar people. Neuropsychological testing indicated that the prosopagnosia probably resulted from the association of an associative/mnemonic mechanism (inability to activate the Face Recognition Units (FRU) from the visual input) and a semantic mechanism (degradation of semantic/biographical information or deconnexion between FRU and this information). At the early stage of the disease, the patient could activate residual semantic information about individuals from their names, but after a 4-year course, he failed to do so. This worsening could be attributed to the extension of the degenerative lesions to the left temporal lobe. Familiar and unfamiliar faces triggered a marked feeling of knowing. False recognition concerned all the unfamiliar faces, and the patient claimed spontaneously that they corresponded to actors, but he could not provide any additional information about their specific identities. The coexistence of prosopagnosia and false recognition suggests the existence of different interconnected systems processing face recognition, one intended to identification of individuals, and the other producing the sense of familiarity. Dysfunctions at different stages of one or the other of these two processes could result in distortions in the feeling of knowing. From this case and others reported in literature, we propose to complete the classical model of face processing

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

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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.

Detection and Differentiation of Frontotemporal Dementia and Related Disorders From Alzheimer Disease Using the Montreal Cognitive Assessment.

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Coleman, Kristy K L; Coleman, Brenda L; MacKinley, Julia D; Pasternak, Stephen H; Finger, Elizabeth C

2016-01-01

The Montreal Cognitive Assessment (MoCA) is a cognitive screening tool used by practitioners worldwide. The efficacy of the MoCA for screening frontotemporal dementia (FTD) and related disorders is unknown. The objectives were: (1) to determine whether the MoCA detects cognitive impairment (CI) in FTD subjects; (2) to determine whether Alzheimer disease (AD) and FTD subtypes and related disorders can be parsed using the MoCA; and (3) describe longitudinal MoCA performance by subtype. We extracted demographic and testing data from a database of patients referred to a cognitive neurology clinic who met criteria for probable AD or FTD (N=192). Logistic regression was used to determine whether dementia subtypes were associated with overall scores, subscores, or combinations of subscores on the MoCA. Initial MoCA results demonstrated CI in the majority of FTD subjects (87%). FTD subjects (N=94) performed better than AD subjects (N=98) on the MoCA (mean scores: 18.1 vs. 16.3; P=0.02). Subscores parsed many, but not all subtypes. FTD subjects had a larger decline on the MoCA within 13 to 36 months than AD subjects (P=0.02). The results indicate that the MoCA is a useful tool to identify and track progression of CI in FTD. Further, the data informs future research on scoring models for the MoCA to enhance cognitive screening and detection of FTD patients.

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.

Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features

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Mahoney, Colin J.; Beck, Jon; Rohrer, Jonathan D.; Lashley, Tammaryn; Mok, Kin; Shakespeare, Tim; Yeatman, Tom; Warrington, Elizabeth K.; Schott, Jonathan M.; Fox, Nick C.; Rossor, Martin N.; Hardy, John; Collinge, John; Revesz, Tamas; Mead, Simon

2012-01-01

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43–68 years) and duration (1.7–22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases

Screening for the C9ORF72 repeat expansion in a greek frontotemporal dementia cohort.

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Kartanou, Chrisoula; Karadima, Georgia; Koutsis, Georgios; Breza, Marianthi; Papageorgiou, Sokratis G; Paraskevas, George P; Kapaki, Elisabeth; Panas, Marios

2018-02-01

The C9orf72 repeat expansion is a common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in European populations. A previous study has reported a high frequency of the expansion in Greek ALS. However, no data have been reported on the frequency of the expansion in Greek FTD. Currently, we investigated the frequency of the C9orfF72 expansion in a well-characterized cohort of 64 Greek FTD patients. We detected the C9orf72 repeat expansion in 9.3% of cases. Overall, 27.7% of familial and 2.2% of sporadic cases were expansion-positive. Five out of 6 cases had a diagnosis of behavioral variant FTD. All expansion-positive cases had fairly typical FTD presentations. Clinical features included motor neuron disease, Parkinsonism and hallucinations. We conclude that the overall frequency of C9orf72-positive cases in Greek FTD is high, comparable to Greek ALS, similar to some Western European, but significantly higher than some Mediterranean FTD populations.

Validation of the German revised Addenbrooke's cognitive examination for detecting mild cognitive impairment, mild dementia in alzheimer's disease and frontotemporal lobar degeneration.

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Alexopoulos, P; Ebert, A; Richter-Schmidinger, T; Schöll, E; Natale, B; Aguilar, C A; Gourzis, P; Weih, M; Perneczky, R; Diehl-Schmid, J; Kneib, T; Förstl, H; Kurz, A; Danek, A; Kornhuber, J

2010-01-01

The diagnostic accuracy of the German version of the revised Addenbrooke's Cognitive Examination (ACE-R) in identifying mild cognitive impairment (MCI), mild dementia in Alzheimer's disease (AD) and mild dementia in frontotemporal lobar degeneration (FTLD) in comparison with the conventional Mini Mental State Examination (MMSE) was assessed. The study encompasses 76 cognitively healthy elderly individuals, 75 patients with MCI, 56 with AD and 22 with FTLD. ACE-R and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic procedure. Statistical analysis was performed using the receiver operating characteristic method and regression analyses. The optimal cut-off score for the ACE-R for detecting MCI, AD, and FTLD was 86/87, 82/83 and 83/84, respectively. ACE-R was superior to MMSE only in the detection of patients with FTLD [area under the curve (AUC): 0.97 vs. 0.92], whilst the accuracy of the two instruments did not differ in identifying MCI and AD. The ratio of the scores of the memory ACE-R subtest to verbal fluency subtest contributed significantly to the discrimination between AD and FTLD (optimal cut-off score: 2.30/2.31, AUC: 0.77), whereas the MMSE and ACE-R total scores did not. The German ACE-R is superior to the most commonly employed MMSE in detecting mild dementia in FTLD and in the differential diagnosis between AD and FTLD. Thus it might serve as a valuable instrument as part of a comprehensive diagnostic workup in specialist centres/clinics contributing to the diagnosis and differential diagnosis of the cause of dementia.

New Perspective on Parkinsonism in Frontotemporal Lobar Degeneration

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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.

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

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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.

Degenerative dementia: nosological aspects and results of single photon emission computed tomography

International Nuclear Information System (INIS)

Dubois, B.; Habert, M.O.

1999-01-01

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.)

The Determinants of Quality of Life of Nursing Home Residents with Young-Onset Dementia and the Differences between Dementia Subtypes

NARCIS (Netherlands)

Appelhof, Britt; Bakker, C.; Van Duinen-van den Ijssel, Jeannette C L; Zwijsen, Sandra A; Smalbrugge, Martin; Verhey, Frans R. J.; de Vugt, Marjolein E; Zuidema, Sytse U.; Koopnnans, Raymond T. C. M.

Aims: The aims of this study are to (1) explore the determinants of quality of life (QoL) in nursing home residents with young-onset dementia (YOD), (2) investigate whether there are differences between dementia subtypes (Alzheimer dementia, vascular/mixed dementia, frontotemporal dementia, other)

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

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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

Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia

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Guo, Christine C.; Sturm, Virginia E.; Zhou, Juan; Gennatas, Efstathios D.; Trujillo, Andrew J.; Hua, Alice Y.; Crawford, Richard; Stables, Lara; Kramer, Joel H.; Rankin, Katherine; Levenson, Robert W.; Rosen, Howard J.; Miller, Bruce L.; Seeley, William W.

2016-01-01

The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have yet to delineate the regions critical for maintaining autonomic outflow. Even greater controversy surrounds hemispheric lateralization along the parasympathetic–sympathetic axis. The behavioral variant of frontotemporal dementia (bvFTD), featuring progressive and often asymmetric degeneration that includes the frontoinsular and cingulate cortices, provides a unique lesion model for elucidating brain structures that control autonomic tone. Here, we show that bvFTD is associated with reduced baseline cardiac vagal tone and that this reduction correlates with left-lateralized functional and structural frontoinsular and cingulate cortex deficits and with reduced agreeableness. Our results suggest that networked brain regions in the dominant hemisphere are critical for maintaining an adaptive level of baseline parasympathetic outflow. PMID:27071080

A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

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Hafkemeijer, Anne; Möller, Christiane; Dopper, Elise G P; Jiskoot, Lize C; van den Berg-Huysmans, Annette A; van Swieten, John C; van der Flier, Wiesje M; Vrenken, Hugo; Pijnenburg, Yolande A L; Barkhof, Frederik; Scheltens, Philip; van der Grond, Jeroen; Rombouts, Serge A R B

2017-01-01

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy. We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63.8±5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups. At baseline, connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls. We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found.

Cerebrospinal Fluid Progranulin, but Not Serum Progranulin, Is Reduced in GRN-Negative Frontotemporal Dementia.

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Wilke, Carlo; Gillardon, Frank; Deuschle, Christian; Hobert, Markus A; Jansen, Iris E; Metzger, Florian G; Heutink, Peter; Gasser, Thomas; Maetzler, Walter; Blauwendraat, Cornelis; Synofzik, Matthis

2017-01-01

Reduced progranulin levels are a hallmark of frontotemporal dementia (FTD) caused by loss-of-function (LoF) mutations in the progranulin gene (GRN). However, alterations of central nervous progranulin expression also occur in neurodegenerative disorders unrelated to GRN mutations, such as Alzheimer's disease. We hypothesised that central nervous progranulin levels are also reduced in GRN-negative FTD. Progranulin levels were determined in both cerebrospinal fluid (CSF) and serum in 75 subjects (37 FTD patients and 38 controls). All FTD patients were assessed by whole-exome sequencing for GRN mutations, yielding a target cohort of 34 patients without pathogenic mutations in GRN (GRN-negative cohort) and 3 GRN mutation carriers (2 LoF variants and 1 novel missense variant). Not only the GRN mutation carriers but also the GRN-negative patients showed decreased CSF levels of progranulin (serum levels in GRN-negative patients were normal). The decreased CSF progranulin levels were unrelated to patients' increased CSF levels of total tau, possibly indicating different destructive neuronal processes within FTD neurodegeneration. The patient with the novel GRN missense variant (c.1117C>T, p.P373S) showed substantially decreased CSF levels of progranulin, comparable to the 2 patients with GRN LoF mutations, suggesting a pathogenic effect of this missense variant. Our results indicate that central nervous progranulin reduction is not restricted to the relatively rare cases of FTD caused by GRN LoF mutations, but also contributes to the more common GRN-negative forms of FTD. Central nervous progranulin reduction might reflect a partially distinct pathogenic mechanism underlying FTD neurodegeneration and is not directly linked to tau alterations. © 2016 S. Karger AG, Basel.

Profile of clinically-diagnosed dementias in a neuropsychiatric ...

African Journals Online (AJOL)

Alzheimer's disease (AD) and Vascular dementia (VaD) were the predominant phenotypes seen in 62 (57.4%) and 18 (16.7%) subjects respectively. Others include mixed dementia (4 cases), frontotemporal dementia (4 cases), Lewy body dementia (3 cases), alcohol-related dementia (3 cases), PD dementia (1 case) and ...

Comparison of QOL between patients with different degenerative dementias, focusing especially on positive and negative affect.

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Kurisu, Kairi; Terada, Seishi; Oshima, Etsuko; Horiuchi, Makiko; Imai, Nao; Yabe, Mayumi; Yokota, Osamu; Ishihara, Takeshi; Yamada, Norihito

2016-08-01

Quality of life (QOL) has become an important outcome measure in the care of dementia patients. However, there have been few studies focusing on the difference in QOL between different dementias. Two-hundred seventy-nine consecutive outpatients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD) were recruited. The QOL was evaluated objectively using the QOL Questionnaire for Dementia (QOL-D).The QOL-D comprises six domains: positive affect, negative affect and actions, communication, restlessness, attachment to others, and spontaneity. General cognition, daily activities, and behavioral and psychological symptoms of dementia were also evaluated. The scores of positive affect of QOL-D of AD patients were significantly higher than those of patients with DLB or FTD (AD 3.1 ± 0.8, DLB 2.6 ± 0.9, FTD 2.6 ± 0.7). The scores of negative affect and action of QOL-D of FTD patients were significantly higher than those of patients with AD or DLB (FTD 2.0 ± 0.8, AD 1.4 ± 0.5, DLB 1.5 ± 0.6). The apathy scores of FTD and DLB patients were significantly higher than those of patients with AD. The disinhibition scores of FTD patients were significantly higher than those of patients with AD or DLB. The apathy of FTD and DLB patients and depression of DLB patients might affect the lower positive affect of FTD and DLB patients compared to AD patients. The disinhibition of FTD patients might affect the abundance of negative affect & actions in FTD patients compared to AD and DLB patients.

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.

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

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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.

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...

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

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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.

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...... in human CHMP2B mutation brain than in neurodegenerative disease or age-matched control brains. These data suggest that lysosomal storage pathology is the major neuronal pathology in FTD caused by CHMP2B mutation. Recent evidence suggests that two other genes associated with FTD, GRN and TMEM106B...... are important for lysosomal function. Our identification of lysosomal storage pathology in FTD caused by CHMP2B mutation now provides evidence that endolysosomal dysfunction is a major degenerative pathway in FTD....

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.

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

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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. Induced...

Brain reserve capacity in frontotemporal dementia: a voxel-based 18F-FDG PET study

International Nuclear Information System (INIS)

Perneczky, Robert; Diehl-Schmid, Janine; Kurz, Alexander; Drzezga, Alexander

2007-01-01

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 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.)

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

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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.

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

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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; St George-Hyslop, Peter; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B; Schlachetzki, Johannes C M; Uphill, James; Collinge, John; Mead, Simon; Danek, Adrian; Van Deerlin, Vivianna M; Grossman, Murray; Trojanowski, 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 A L; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A; Franceschi, Massimo; 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

2014-07-01

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. We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of 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)) single-nucleotide polymorphisms. We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10(-8)). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10(-8); odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10(-9); 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10(-8), 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10(-7); 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data

Enhanced Positive Emotional Reactivity Undermines Empathy in Behavioral Variant Frontotemporal Dementia

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Alice Y. Hua

2018-06-01

Full Text Available Behavioral variant frontotemporal dementia (bvFTD is a neurodegenerative disease characterized by profound changes in emotions and empathy. Although most patients with bvFTD become less sensitive to negative emotional cues, some patients become more sensitive to positive emotional stimuli. We investigated whether dysregulated positive emotions in bvFTD undermine empathy by making it difficult for patients to share (emotional empathy, recognize (cognitive empathy, and respond (real-world empathy to emotions in others. Fifty-one participants (26 patients with bvFTD and 25 healthy controls viewed photographs of neutral, positive, negative, and self-conscious emotional faces and then identified the emotions displayed in the photographs. We used facial electromyography to measure automatic, sub-visible activity in two facial muscles during the task: Zygomaticus major (ZM, which is active during positive emotional reactions (i.e., smiling, and Corrugator supercilii (CS, which is active during negative emotional reactions (i.e., frowning. Participants rated their baseline positive and negative emotional experience before the task, and informants rated participants' real-world empathic behavior on the Interpersonal Reactivity Index. The majority of participants also underwent structural magnetic resonance imaging. A mixed effects model found a significant diagnosis X trial interaction: patients with bvFTD showed greater ZM reactivity to neutral, negative (disgust and surprise, self-conscious (proud, and positive (happy faces than healthy controls. There was no main effect of diagnosis or diagnosis X trial interaction on CS reactivity. Compared to healthy controls, patients with bvFTD had impaired emotion recognition. Multiple regression analyses revealed that greater ZM reactivity predicted worse negative emotion recognition and worse real-world empathy. At baseline, positive emotional experience was higher in bvFTD than healthy controls and also

Word list and story recall elicit different patterns of memory deficit in patients with Alzheimer's disease, frontotemporal dementia, subcortical ischemic vascular disease, and Lewy body dementia.

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Perri, Roberta; Fadda, Lucia; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2013-01-01

Different roles have been attributed to mesio-temporal areas and frontal lobes in declarative memory functioning, and qualitative differences have been observed in the amnesic symptoms due to pathological damage of these two portions of the central nervous system. The aim of the present study was to look for memory profiles related to pathological involvement in the temporal and frontal structures in patients with different dementia syndromes on word-list and prose memory tasks. 20 patients with Alzheimer's disease (AD), 20 with frontal variant of FTD (fvFTD), 20 with subcortical ischemic vascular dementia (SIVD), and 20 with Lewy body dementia (LBD) and 34 healthy subjects (NCs) were submitted to word-list and prose memory tasks. All groups performed similarly on both the immediate and delayed recall of the word-list. Conversely, AD patients performed worse than all the other dementia groups on the immediate prose recall. On delayed prose recall, AD patients performed worse than fvFTD and SIVD patients but similar to LBD patients. Differential scores between word-list and prose tests were minimal in the AD group and very pronounced in fvFTD and SIVD groups. The combined use of the prose and word-list tasks evidenced a "mesio-temporal" memory profile in AD patients as opposed to a "frontal" one in fvFTD and SIVD patients and a mixed profile in the LBD patients. In particular, a differential score between the two tests can be useful in differentiating AD patients from patients with other forms of dementia.

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

International Nuclear Information System (INIS)

Lee, Myoung Hoon; Park, Chan H.; Yoon, Seok Na.; Hwang, Kyung Hoon

2001-01-01

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

The behavioral variant of frontotemporal dementia: An analysis of the literature and a case report.

Science.gov (United States)

Birkhoff, Jutta Maria; Garberi, Cesare; Re, Laura

2016-01-01

The aim of this case report is to underline the importance of possible legal consequences of the behavioral variant of frontotemporal dementia (bvFTD). This disease is associated with antisocial behavior, impulse control disorder and cognitive and personality impairment, which are often the earliest manifestations of the bvFTD. One of the antisocial behaviors possibly associated with this neurodegenerative disease is pathological stealing. This case report is about a 50-year-old Italian man who had a regular life until 2010. In 2010 and 2011, some critical events occurred: he lost his job, his father-in-law, to whom he was particularly close, died, and his wife had a serious illness. He began to show symptoms of depression, a significant weight loss, apathy, poor self-care, and lack of interest in the activities of his family. He became disengaged from his prior activities, emotionally detached from his family and developed compulsive hoarding. Moreover, he had uninhibited behaviors, a memory retrieval deficit, executive dysfunctions and impulsive behaviors. In January 2012, the subject began stealing objects, particularly components of computer, without premeditation or concern for resulting legal actions. He was then diagnosed affected by bvFTD. He was charged with theft and attempted theft and the Court asked for a psychiatric evaluation, in order to analyze the effect of the neurodegenerative disease on his behavior. To answer to the Court, the Authors analyzed his history of life and made a mental examination. The subject was considered mentally insane at the time of his crimes. This is an example of the practical application in judicial cases of the latest knowledge and evidence in the literature about the frontotemporal dementia, a disease associated with antisocial behaviors that could create tensions with the criminal law. The focus of the paper is to explain how the behavioral symptoms of bvFTD can have legal implications and how to deal with legal

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

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

Genetics of Frontotemporal Lobar Degeneration

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Daniela eGalimberti

2012-04-01

Full Text Available Frontotemporal Lobar Degeneration (FTLD is the most frequent neurodegenerative disorder with a presenile onset. It presents with a spectrum of clinical manifestations, ranging from behavioural and executive impairment to language disorders and motor dysfunction. Familial aggregation is frequently reported in FTLD, and about 10% of cases have an autosomal dominant transmission. Microtubule Associated Protein Tau gene (MAPT mutations have been the first ones identified and are generally associated with early onset behavioural variant Frontotemporal Dementia (bvFTD phenotype. More recently, progranulin gene (GRN mutations were recognized in association with familial form of FTLD. In addition, other genes are linked to rare cases of familial FTLD. Lastly, a number of genetic risk factors for sporadic forms have also been identified.

Can cognitive assessment really discriminate early stages of Alzheimer's and behavioural variant frontotemporal dementia at initial clinical presentation?

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Reul, Sophia; Lohmann, Hubertus; Wiendl, Heinz; Duning, Thomas; Johnen, Andreas

2017-08-09

Neuropsychological testing is considered crucial for differential diagnosis of Alzheimer's disease (AD) and behavioural variant frontotemporal dementia (bvFTD). In-depth neuropsychological assessment revealed specific dysfunctions in the two dementia syndromes. However, a significant overlap of cognitive impairments exists in early disease stages. We questioned whether a standard neuropsychological assessment at initial clinical presentation can delineate patients with AD versus bvFTD. In a retrospective approach, we evaluated and compared how cognitive profiles assessed at initial clinical presentation predicted the diagnosis of later verified AD (n = 43) and bvFTD (n = 26). Additionally, the neuropsychological standard domains memory, language, visuospatial skills, executive functions, praxis and social cognition were subjected to stepwise discriminant analysis to compare their differential contribution to diagnosis. Regardless of diagnosis, a percentage of patients presented with major deterioration in a wide range of cognitive domains when compared with age-matched normative data. Only few significant differences were detected on the group level: Patients with AD were relatively more impaired in the verbal recall, verbal recognition, figure copy, and surprisingly in the executive subdomains, set shifting and processing speed whereas bvFTD was characterised by more deficits in imitation of face postures. A combination of tests for verbal recall, imitation of limb and face postures, and figure copy showed the greatest discriminatory power. Our results imply that the contribution of a standard neuropsychological assessment is limited for differential diagnosis of AD and bvFTD at initial presentation. In contrast to current clinical guidelines, executive functions are neither particularly nor exclusively impaired in patients with bvFTD when assessed within a standard clinical neuropsychological test battery. The significant overlap of bvFTD and AD

Generation of an isogenic, gene-corrected iPSC line from a symptomatic 59-year-old female patient with frontotemporal dementia caused by an R406W mutation in the microtubule associated protein tau (MAPT) gene

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Nimsanor, Natakarn; Poulsen, Ulla; Rasmussen, Mikkel A.

2016-01-01

pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a 59-year-old female FTD-17 patient carrying an R406W mutation in the MAPT-gene....

Generation of an isogenic, gene-corrected iPSC line from a symptomatic 57-year-old female patient with frontotemporal dementia caused by a P301L mutation in the microtubule associated protein tau (MAPT) gene

DEFF Research Database (Denmark)

Nimsanor, Natakarn; Kitiyanant, Narisorn; Poulsen, Ulla

2016-01-01

pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau)-gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a 57-year-old female FTD-17 patient carrying an P301L mutation in the MAPT-gene....

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia.

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Le Ber, Isabelle; De Septenville, Anne; Guerreiro, Rita; Bras, José; Camuzat, Agnès; Caroppo, Paola; Lattante, Serena; Couarch, Philippe; Kabashi, Edor; Bouya-Ahmed, Kawtar; Dubois, Bruno; Brice, Alexis

2014-10-01

TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous mutation in a new consanguineous Italian family. Two sibs had early onset autosomal recessive FTLD without severe bone disorders. Atypical signs were present in this family: early parietal and hippocampus involvement, parkinsonism, epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This study further demonstrates the implication of TREM2 mutations in FTLD phenotypes. It illustrates the variability of bone phenotype and underlines the frequency of atypical signs in TREM2 carriers. This and previous studies evidence that TREM2 mutation screening should be limited to autosomal recessive FTLD with atypical phenotypes characterized by: (1) a very young age at onset (20-50 years); (2) early parietal and hippocampal deficits; (3) the presence of seizures and parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum thickness on brain magnetic resonance imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Sensitivity of the Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-II) to the neurocognitive deficits associated with the semantic dementia variant of frontotemporal lobar degeneration: A case study.

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Gontkovsky, Samuel T

2017-01-01

This case study of a 71-year-old woman illustrates the clinical utility of the Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-II) in assessing the neurocognitive sequelae of the semantic dementia variant of frontotemporal lobar degeneration. Obtained scores revealed a decline in estimated Full Scale IQ from the patient's expected premorbid level. Consistent with her initial onset of neuropathology in the left temporal lobe, the WASI-II yielded a difference of 53 standard score points between the Perceptual Reasoning and Verbal Comprehension composites, reflecting the patient's intact capabilities in visuospatial perception and construction in conjunction with marked disturbances of language. The similarities subtest was particularly sensitive to the patient's neurocognitive deficits. WASI-II scores corresponded well with the results obtained from other administered measures, in particular those from the Repeatable Battery for the Assessment of Neuropsychological Status. Findings provide support for use of the WASI-II in the clinical evaluation of semantic dementia and offer preliminary evidence that the test may be helpful in both lateralization and localization of brain lesions.

The structural neuroanatomy of music emotion recognition: evidence from frontotemporal lobar degeneration.

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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. Copyright © 2011 Elsevier Inc. All rights reserved.

Neuropsychological Testing in Pathologically Verified Alzheimer Disease and Frontotemporal Dementia: How Well Do the Uniform Data Set Measures Differentiate Between Diseases?

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Ritter, Aaron R; Leger, Gabriel C; Miller, Justin B; Banks, Sarah J

2017-01-01

Differences in cognition between frontotemporal dementia (FTD) and Alzheimer disease (AD) are well described in clinical cohorts, but have rarely been confirmed in studies with pathologic verification. For emerging therapeutics to succeed, determining underlying pathology early in the disease course is increasingly important. Neuropsychological evaluation is an important component of the diagnostic workup for AD and FTD. Patients with FTD are thought to have greater deficits in language and executive function while patients with AD are more likely to have deficits in memory. To determine if performance on initial cognitive testing can reliably distinguish between patients with frontotemporal lobar degeneration (FTLD) and AD neuropathology. In addition, are there other factors of the neuropsychological assessment that can be used to enhance the accuracy of underlying pathology? Using a logistic regression we retrospectively compared neurocognitive performance on initial evaluation of 106 patients with pathologically verified FTLD (pvFTLD), with 558 pathologically verified AD (pvAD) patients from the National Alzheimer's Coordinating Center using data from the Uniform Data Set (UDS) and the neuropathology data set. As expected, pvFTLD patients were younger, demonstrated better memory performance, and had more neuropsychiatric symptoms than pvAD patients. Other results were less predictable: pvFTLD patients performed better on one test of executive function (trail making test part B) but worse on another (digit span backward). Performance on language testing did not strongly distinguish the 2 groups. To determine what factors led to a misdiagnosis of AD in patients with FTLD, we further analyzed a small group of pvFTLD patients. These patients demonstrated older age and lower Neuropsychiatric Inventory Questionnaire counts compared with accurately diagnosed cases. Other than memory, numerical scores of neurocognitive performance on the UDS are of limited value in

[Artistic creativity and dementia].

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Sellal, François; Musacchio, Mariano

2008-03-01

Artistic creativity can be defined as the ability to produce both innovative and esthetic works. Though most dementias result in a loss of instrumental functions and a deterioration in artistic production, for some established artists, dementia, most often Alzheimer's disease, changed their style and technique but preserved their creativity and prolific artistic drive. Moreover, in some cases, mainly frontotemporal dementia, Parkinson's disease, and very occasionally strokes, the disease may favour the emergence of de novo artistic talent. This phenomenon has been conceptualized as a paradoxical facilitation, a disinhibition of brain areas devoted to visuospatial processing, greater freedom in a patient who becomes less bound by social conventions, enhancement of motivation and pleasure, etc. These neurological cases provide an opportunity to shed some light on the roots of artistic creation.

The Relationship between Subclinical Asperger’s Syndrome and Frontotemporal Lobar Degeneration

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Akira Midorikawa

2012-04-01

Full Text Available Background/Aims: The existence of the behavioral variant of frontotemporal dementia (bv-FTD, including senile Asperger’s syndrome (AS, has been proposed. However, there are no empirical case reports to support the proposal. In this report, we present 3 patients who showed symptoms of bv-FTD and demonstrated signs of autistic spectrum disorder, especially AS. Methods: We evaluated 3 subjects using the diagnostic criteria for bv-FTD, and their caregivers retrospectively provided data to calculate the Autism-Spectrum Quotient, Japanese version [Wakabayashi et al.: Shinrigaku Kenkyu 2004;75:78–84]. We also compared these data with those obtained from 3 individuals with Alzheimer’s disease. Results: All 3 patients met the criteria for bv-FTD and had a higher Autism-Spectrum Quotient score than did comparable Alzheimer’s disease subjects. Conclusion: It is possible that some senile persons with frontotemporal lobar degeneration-like maladaptive behavior may suffer from subclinical AS.

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

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Anauate, Maria Cristina; Bahia, Valéria Santoro; Nitrini, Ricardo; Radanovic, Marcia

2014-01-01

Several studies have addressed visuospatial and executive skills in artistic activities in Frontotemporal Lobar Degeneration (FTLD) and Alzheimer's disease (AD). To investigate the performance of FTLD patients compared to controls on two artistic tasks. 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. 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. 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.

The frontotemporal syndrome of ALS is associated with poor survival.

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Govaarts, Rosanne; Beeldman, Emma; Kampelmacher, Mike J; van Tol, Marie-Jose; van den Berg, Leonard H; van der Kooi, Anneke J; Wijkstra, Peter J; Zijnen-Suyker, Marianne; Cobben, Nicolle A M; Schmand, Ben A; de Haan, Rob J; de Visser, Marianne; Raaphorst, Joost

2016-12-01

Thirty percent of ALS patients have a frontotemporal syndrome (FS), defined as behavioral changes or cognitive impairment. Despite previous studies, there are no firm conclusions on the effect of the FS on survival and the use of non-invasive ventilation (NIV) in ALS. We examined the effect of the FS on survival and the start and duration of NIV in ALS. Behavioral changes were defined as >22 points on the ALS-Frontotemporal-Dementia-Questionnaire or ≥3 points on ≥2 items of the Neuropsychiatric Inventory. Cognitive impairment was defined as below the fifth percentile on ≥2 tests of executive function, memory or language. Classic ALS was defined as ALS without the frontotemporal syndrome. We performed survival analyses from symptom onset and time from NIV initiation, respectively, to death. The impact of the explanatory variables on survival and NIV initiation were examined using Cox proportional hazards models. We included 110 ALS patients (76 men) with a mean age of 62 years. Median survival time was 4.3 years (95 % CI 3.53-5.13). Forty-seven patients (43 %) had an FS. Factors associated with shorter survival were FS, bulbar onset, older age at onset, short time to diagnosis and a C9orf72 repeat expansion. The adjusted hazard ratio (HR) for the FS was 2.29 (95 % CI 1.44-3.65, p NIV initiation (adjusted HR 2.70, 95 % CI 1.04-4.67, p = 0.04). In conclusion, there is an association between the frontotemporal syndrome and poor survival in ALS, which remains present after initiation of NIV.

Guidance for reading FDG PET scans in dementia patients

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Herholz, K.

2014-01-01

18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is a powerful method for detection of disease-related impairment of cerebral glucose metabolism in neuro degenerative diseases. It is of particular interest for early and differential diagnosis of dementia. Reading FDG PET scans requires training to recognise deviations from normal functional brain anatomy and its variations. This paper provides guidance for displaying FDG PET brain scans in a reproducible manner that allows reliable recognition of characteristic disease-related metabolic changes. It also describes typical findings in Alzheimer’s disease, Frontotemporal Dementia and Dementia with Lewy Bodies and possible confounding factors, such as vascular changes and brain atrophy. It provides a brief overview on findings in other neuro degenerative diseases and addresses the potential and limitations of software packages for comparison of individual scans with reference data.

Frontal and temporal lobe contributions to emotional enhancement of memory in behavioural-variant frontotemporal dementia and Alzheimer's disease

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Fiona eKumfor

2014-06-01

Full Text Available Emotional events gain special priority in how they are remembered, with emotionally arousing events typically recalled more vividly and with greater confidence than non-emotional events. In dementia, memory and emotion processing are affected to varying degrees, however, whether emotional enhancement of memory for complex ecologically valid events is differentially affected across dementia syndromes remains unclear, with previous studies examining effects of emotion on simple visual recognition only. Here, we examined memory for an emotionally arousing short story and a closely matched, emotionally neutral story in behavioural-variant frontotemporal dementia (bvFTD (n = 13 and Alzheimer’s disease (AD (n = 14, and contrasted their performance with healthy controls (n = 12. Multiple-choice recognition memory for specific details of the story was assessed after a 1-hour delay. While AD and control groups showed enhanced memory for the emotional story, the bvFTD group recalled a similar number of details from the emotional and neutral stories. Voxel-based morphometry analyses revealed emotional enhancement of memory correlated with distinct brain regions in each patient group. In AD, emotional enhancement was associated with integrity of the bilateral hippocampus, parahippocampal gyri, temporal fusiform gyrus and frontal pole, regions implicated in memory processes. In contrast in bvFTD, integrity of emotion processing regions, including the orbitofrontal cortex, right amygdala and right insula, correlated with the extent emotion enhanced memory. Our results reveal that integrity of frontal and temporal regions determine the quality and nature of emotional memories. While emotional enhancement of memory is present in mild AD, in bvFTD emotion does not facilitate memory retrieval for complex realistic events. This attenuation of emotional enhancement is due to degradation of emotion processing regions, which may be important for modulating levels

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

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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.)

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

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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.

Murine knockin model for progranulin-deficient frontotemporal dementia with nonsense-mediated mRNA decay.

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Nguyen, Andrew D; Nguyen, Thi A; Zhang, Jiasheng; Devireddy, Swathi; Zhou, Ping; Karydas, Anna M; Xu, Xialian; Miller, Bruce L; Rigo, Frank; Ferguson, Shawn M; Huang, Eric J; Walther, Tobias C; Farese, Robert V

2018-03-20

Frontotemporal dementia (FTD) is the most common neurodegenerative disorder in individuals under age 60 and has no treatment or cure. Because many cases of FTD result from GRN nonsense mutations, an animal model for this type of mutation is highly desirable for understanding pathogenesis and testing therapies. Here, we generated and characterized Grn R493X knockin mice, which model the most common human GRN mutation, a premature stop codon at arginine 493 (R493X). Homozygous Grn R493X mice have markedly reduced Grn mRNA levels, lack detectable progranulin protein, and phenocopy Grn knockout mice, with CNS microgliosis, cytoplasmic TDP-43 accumulation, reduced synaptic density, lipofuscinosis, hyperinflammatory macrophages, excessive grooming behavior, and reduced survival. Inhibition of nonsense-mediated mRNA decay (NMD) by genetic, pharmacological, or antisense oligonucleotide-based approaches showed that NMD contributes to the reduced mRNA levels in Grn R493X mice and cell lines and in fibroblasts from patients containing the GRN R493X mutation. Moreover, the expressed truncated R493X mutant protein was functional in several assays in progranulin-deficient cells. Together, these findings establish a murine model for in vivo testing of NMD inhibition or other therapies as potential approaches for treating progranulin deficiency caused by the R493X mutation. Copyright © 2018 the Author(s). Published by PNAS.

Factors associated with a depressive disorder in Alzheimer's disease are different from those found for other dementia disorders.

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Barca, Maria Lage; Engedal, Knut; Laks, Jerson; Selbaek, Geir

2012-01-01

This study explores factors associated with depression in Alzheimer's disease (AD) compared with mild cognitive impairment (MCI) and other dementia disorders. In a prospective study we included 195 patients: 31 with MCI, 112 with AD and 52 with other dementias. 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. We found different factors associated with a depressive disorder in AD compared to those found for other dementia disorders.

The different faces of the p. A53T alpha-synuclein mutation: A screening of Greek patients with parkinsonism and/or dementia.

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Breza, Marianthi; Koutsis, Georgios; Karadima, Georgia; Potagas, Constantin; Kartanou, Chrisoula; Papageorgiou, Sokratis G; Paraskevas, George P; Kapaki, Elisabeth; Stefanis, Leonidas; Panas, Marios

2018-04-13

The p. A53T mutation in the alpha-synuclein (SNCA) gene is a rare cause of autosomal dominant Parkinson's disease (PD). Although generally rare, it is particularly common in the Greek population due to a founder effect. A53T-positive PD patients often develop dementia during disease course and may very rarely present with dementia. We screened for the p. A53T SNCA mutation a total of 347 cases of Greek origin with parkinsonism and/or dementia, collected over 15 years at the Neurogenetics Unit, Eginition Hospital, University of Athens. Cases were classified into: "pure parkinsonism", "pure dementia" and "parkinsonism plus dementia". In total, 4 p. A53T SNCA mutation carriers were identified. All had autosomal dominant family history and early onset. Screening of the "pure parkinsonism" category revealed 2 cases with typical PD. The other two mutation carriers were identified in the "parkinsonism plus dementia" category. One had a diagnosis of PD dementia and the other of behavioral variant frontotemporal dementia. Screening of patients with "pure dementia" failed to identify any further A53T-positive cases. Our results confirm that the p. A53T SNCA mutation is relatively common in Greek patients with PD or PD plus dementia, particularly in cases with early onset and/or autosomal dominant family history. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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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

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

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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.)

Episodic Memory Dysfunction in Behavioral Variant Frontotemporal Dementia: A Clinical And FDG-PET Study.

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Fernández-Matarrubia, Marta; Matías-Guiu, Jordi A; Cabrera-Martín, María Nieves; Moreno-Ramos, Teresa; Valles-Salgado, María; Carreras, José Luis; Matías-Guiu, Jorge

2017-01-01

Episodic memory disturbance is still considered as an exclusion criterion for behavioral variant frontotemporal dementia (bvFTD), but growing evidence suggests that memory can be impaired. Our main purposes were to assess episodic memory in a group of bvFTD patients comparatively with Alzheimer's disease (AD) patients, and analyze the relationship between episodic memory and brain metabolism measured using positron emission tomography imaging with 18F-fluorodeoxyglucose (FDG-PET). Twenty-six bvFTD, 29 AD, and 24 healthy controls were included. Episodic memory was assessed by the Free and Cued Selective Reminding Test (FCSRT), which controls for effective encoding and measures memory consolidation processing. All participants underwent FDG-PET brain scans to provide data for voxel-based brain mapping analysis. Half of bvFTD patients had a deficit of total, free delayed, and total free delayed recall as severe as AD patients (amnestic-FTD). The other half had FCSRT scores similar to controls (non-amnestic-FTD). Imaging analyses revealed that amnestic-FTD showed bilateral lower metabolism than non-amnestic-FTD in anterior parahippocampal and inferior temporal gyri. Additionally, FCSRT total and total delayed scores were inversely correlated with parahippocampal metabolism in both bvFTD and AD. Besides, bvFTD showed an inverse association among FCSRT and inferior temporal metabolism. Our findings support that bvFTD could present a genuine amnesia affecting storage and consolidation abilities, which involves structures implicated in the Papez circuit, as occurs in AD, and also inferior temporal regions. These results contribute to understanding the mechanisms underpinning memory dysfunction in bvFTD, and may be relevant to further revisions of the current diagnostic criteria.

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

Directory of Open Access Journals (Sweden)

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.

Weighted Protein Interaction Network Analysis of Frontotemporal Dementia.

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Ferrari, Raffaele; Lovering, Ruth C; Hardy, John; Lewis, Patrick A; Manzoni, Claudia

2017-02-03

The genetic analysis of complex disorders has undoubtedly led to the identification of a wealth of associations between genes and specific traits. However, moving from genetics to biochemistry one gene at a time has, to date, rather proved inefficient and under-powered to comprehensively explain the molecular basis of phenotypes. Here we present a novel approach, weighted protein-protein interaction network analysis (W-PPI-NA), to highlight key functional players within relevant biological processes associated with a given trait. This is exemplified in the current study by applying W-PPI-NA to frontotemporal dementia (FTD): We first built the state of the art FTD protein network (FTD-PN) and then analyzed both its topological and functional features. The FTD-PN resulted from the sum of the individual interactomes built around FTD-spectrum genes, leading to a total of 4198 nodes. Twenty nine of 4198 nodes, called inter-interactome hubs (IIHs), represented those interactors able to bridge over 60% of the individual interactomes. Functional annotation analysis not only reiterated and reinforced previous findings from single genes and gene-coexpression analyses but also indicated a number of novel potential disease related mechanisms, including DNA damage response, gene expression regulation, and cell waste disposal and potential biomarkers or therapeutic targets including EP300. These processes and targets likely represent the functional core impacted in FTD, reflecting the underlying genetic architecture contributing to disease. The approach presented in this study can be applied to other complex traits for which risk-causative genes are known as it provides a promising tool for setting the foundations for collating genomics and wet laboratory data in a bidirectional manner. This is and will be critical to accelerate molecular target prioritization and drug discovery.

Physiological phenotyping of dementias using emotional sounds.

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Fletcher, Phillip D; Nicholas, Jennifer M; Shakespeare, Timothy J; Downey, Laura E; Golden, Hannah L; Agustus, Jennifer L; Clark, Camilla N; Mummery, Catherine J; Schott, Jonathan M; Crutch, Sebastian J; Warren, Jason D

2015-06-01

Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds. Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age-matched individuals (n = 26). Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds. Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development.

Physical Activity Prevents Progression for Cognitive Impairment and Vascular Dementia

DEFF Research Database (Denmark)

Verdelho, Ana; Madureira, Sofia; Ferro, José M

2012-01-01

BACKGROUND AND PURPOSE: We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. METHODS: The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates....... Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. RESULTS: Six hundred thirty-nine subjects were included (74.1±5 years old, 55% women, 9.6±3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia...... (vascular dementia, 54; Alzheimer disease with vascular component, 34; frontotemporal dementia, 2), and 147 had cognitive impairment not dementia. Using Cox regression analysis, physical activity reduced the risk of cognitive impairment (dementia and not dementia: β=-0.45, P=0.002; hazard ratio, 0.64; 95...

Art and the brain: a view from dementia.

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Gretton, Cosima; ffytche, Dominic H

2014-02-01

Art making encompasses a range of perceptual and cognitive functions involving widely distributed brain systems. The dementias impact on these systems in different ways, raising the possibility that each dementia has a unique artistic signature. Here we use a review of the visual art of 14 artists with dementia (five Alzheimer's disease, seven fronto-temporal dementia and two dementia with Lewy bodies) to further our understanding of the neurobiological constituents of art production and higher artistic function. Artists with Alzheimer's disease had prominent changes in spatial aspects of their art and attributes of colour and contrast. These qualities were preserved in the art of fronto-temporal dementia, which was characterised by perseverative themes and a shift towards realistic representation. The art of dementia with Lewy Bodies was characterised by simple, bizarre content. The limitations of using visual aspects of individual artworks to infer the impact of dementia on art production are discussed with the need for a wider perspective encompassing changes in cognition, emotion, creativity and artistic personality. A novel classificatory scheme is presented to help characterise neural mechanisms of higher artistic functions in future studies. Copyright © 2013 John Wiley & Sons, Ltd.

Parsing cognitive and emotional empathy deficits for negative and positive stimuli in frontotemporal dementia.

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Oliver, Lindsay D; Mitchell, Derek G V; Dziobek, Isabel; MacKinley, Julia; Coleman, Kristy; Rankin, Katherine P; Finger, Elizabeth C

2015-01-01

Behavioural variant frontotemporal dementia (bvFTD) is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe atrophy primarily affecting social cognition and emotion, including loss of empathy. Many consider empathy to be a multidimensional construct, including cognitive empathy (the ability to adopt and understand another's perspective) and emotional empathy (the capacity to share another's emotional experience). Cognitive and emotional empathy deficits have been associated with bvFTD; however, little is known regarding the performance of patients with bvFTD on behavioural measures of emotional empathy, and whether empathic responses differ for negative versus positive stimuli. 24 patients with bvFTD and 24 healthy controls completed the Multifaceted Empathy Test (MET; Dziobek et al., 2008), a performance-based task that taps both cognitive and emotional facets of empathy, and allows for the discrimination of responses to negative versus positive realistic images. MET scores were also compared with caregiver ratings of patient behaviour on the Interpersonal Reactivity Index, which assesses patients' everyday demonstrations of perspective taking and empathic concern. Patients with bvFTD were less accurate than controls at inferring mental states for negative and positive stimuli. They also demonstrated lower levels of shared emotional experience, more positive emotional reactions, and diminished arousal to negative social stimuli relative to controls. Patients showed reduced emotional reactions to negative non-social stimuli as well. Lastly, the MET and IRI measures of emotional empathy were found to be significantly correlated within the bvFTD group. The results suggest that patients with bvFTD show a global deficit in cognitive empathy, and deficient emotional empathy for negative, but not positive, experiences. Further, a generalized emotional processing impairment for negative stimuli was observed, which could contribute to the

Frontotemporal lobar degeneration: current perspectives

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Riedl L

2014-02-01

Full Text Available Lina Riedl,1 Ian R Mackenzie,2 Hans Förstl,1 Alexander Kurz,1 Janine Diehl-Schmid1 1Center for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; 2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada Abstract: The term frontotemporal lobar degeneration (FTLD refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer's disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT, the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN, and in the chromosome 9 open reading frame 72 (C9orf72 accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake

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

International Nuclear Information System (INIS)

Bron, Esther E.; Klein, Stefan; Smits, Marion; Steketee, Rebecca M.E.; Meijboom, Rozanna; Papma, Janne M.; Swieten, John C. van; Groot, Marius de; Niessen, Wiro J.

2017-01-01

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. This retrospective study used MRI data from 24 early-onset AD and 33 early-onset FTD patients and 34 controls (CN). Classification was based on voxel-wise feature maps derived from structural MRI, ASL, and DTI. Support vector machines (SVMs) were trained to classify AD versus CN (AD-CN), FTD-CN, AD-FTD, and AD-FTD-CN (multi-class). Classification performance was assessed by the area under the receiver-operating-characteristic curve (AUC) and accuracy. Using SVM significance maps, we analysed contributions of brain regions. Combining ASL and DTI with structural MRI resulted in higher classification performance for differential diagnosis of AD and FTD (AUC = 84%; p = 0.05) than using structural MRI by itself (AUC = 72%). The performance of ASL and DTI themselves did not improve over structural MRI. The classifications were driven by different brain regions for ASL and DTI than for structural MRI, suggesting complementary information. ASL and DTI are promising additions to structural MRI for classification of early-onset AD, early-onset FTD, and controls, and may improve the computer-aided differential diagnosis on a single-subject level. (orig.)

Internet-based screening for dementia risk.

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Brandt, Jason; Sullivan, Campbell; Burrell, Larry E; Rogerson, Mark; Anderson, Allan

2013-01-01

The Dementia Risk Assessment (DRA) is an online tool consisting of questions about known risk factors for dementia, a novel verbal memory test, and an informant report of cognitive decline. Its primary goal is to educate the public about dementia risk factors and encourage clinical evaluation where appropriate. In Study 1, more than 3,000 anonymous persons over age 50 completed the DRA about themselves; 1,000 people also completed proxy reports about another person. Advanced age, lower education, male sex, complaints of severe memory impairment, and histories of cerebrovascular disease, Parkinson's disease, and brain tumor all contributed significantly to poor memory performance. A high correlation was obtained between proxy-reported decline and actual memory test performance. In Study 2, 52 persons seeking first-time evaluation at dementia clinics completed the DRA prior to their visits. Their responses (and those of their proxy informants) were compared to the results of independent evaluation by geriatric neuropsychiatrists. The 30 patients found to meet criteria for probable Alzheimer's disease, vascular dementia, or frontotemporal dementia differed on the DRA from the 22 patients without dementia (most other neuropsychiatric conditions). Scoring below criterion on the DRA's memory test had moderately high predictive validity for clinically diagnosed dementia. Although additional studies of larger clinical samples are needed, the DRA holds promise for wide-scale screening for dementia risk.

Progranulin mutation causes frontotemporal dementia in the Swedish Karolinska family.

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Chiang, Huei-Hsin; Rosvall, Lina; Brohede, Jesper; Axelman, Karin; Björk, Behnosh F; Nennesmo, Inger; Robins, Tiina; Graff, Caroline

2008-11-01

Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by cognitive impairment, language dysfunction, and/or changes in personality. Recently it has been shown that progranulin (GRN) mutations can cause FTD as well as other neurodegenerative phenotypes. DNA from 30 family members, of whom seven were diagnosed with FTD, in the Karolinska family was available for GRN sequencing. Fibroblast cell mRNA from one affected family member and six control individuals was available for relative quantitative real-time polymerase chain reaction to investigate the effect of the mutation. Furthermore, the cDNA of an affected individual was sequenced. Clinical and neuropathologic findings of a previously undescribed family branch are presented. A frameshift mutation in GRN (g.102delC) was detected in all affected family members and absent in four unaffected family members older than 70 years. Real-time polymerase chain reaction data showed an approximately 50% reduction of GRN fibroblast mRNA in an affected individual. The mutated mRNA transcripts were undetectable by cDNA sequencing. Segregation and RNA analyses showed that the g.102delC mutation, previously reported, causes FTD in the Karolinska family. Our findings add further support to the significance of GRN in FTD etiology and the presence of modifying genes, which emphasize the need for further studies into the mechanisms of clinical heterogeneity. However, the results already call for attention to the complexity of predictive genetic testing of GRN mutations.

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

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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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Invited review: Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging.

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Ghetti, B; Oblak, A L; Boeve, B F; Johnson, K A; Dickerson, B C; Goedert, M

2015-02-01

Hereditary frontotemporal dementia associated with mutations in the microtubule-associated protein tau gene (MAPT) is a protean disorder. Three neuropathologic subtypes can be recognized, based on the presence of inclusions made of tau isoforms with three and four repeats, predominantly three repeats and mostly four repeats. This is relevant for establishing a correlation between structural magnetic resonance imaging and positron emission tomography using tracers specific for aggregated tau. Longitudinal studies will be essential to determine the evolution of anatomical alterations from the asymptomatic stage to the various phases of disease following the onset of symptoms. © 2014 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

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

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

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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.

Telephone-Based Cognitive-Behavioral Screening for Frontotemporal Changes in Patients with Amyotrophic Lateral Sclerosis (ALS)

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Christodoulou, Georgia; Gennings, Chris; Hupf, Jonathan; Factor-Litvak, Pam; Murphy, Jennifer; Goetz, Raymond R.; Mitsumoto, Hiroshi

2017-01-01

Objective To establish a valid and reliable battery of measures to evaluate frontotemporal dementia (FTD) in patients with ALS over the phone. Methods Thirty-one subjects were administered either in-person or telephone-based screening followed by the opposite mode of testing two weeks later, using a modified version of the UCSF Cognitive Screening Battery. Results Equivalence testing was performed for in-person and telephone-based tests. The standard ALS Cognitive Behavioral Screen (ALS-CBS) showed statistical equivalence at the 5% significance level when compared to a revised phone-version of the ALS-CBS. In addition, the Controlled Oral Word Association Test (COWAT) and Center for Neurologic Study-Lability Scale (CNS-LS) were also found to be equivalent at the 5% and 10% significance level respectively. Similarly, the Mini-Mental State Examination (MMSE) and the well-established Telephone Interview for Cognitive Status (TICS) were also statistically equivalent. Equivalence could not be claimed for the ALS-Frontal Behavioral Inventory (ALS-FBI) caregiver interview and the Written Verbal Fluency Index (WVFI). Conclusions Our study suggests that telephone-based versions of the ALS-CBS, COWAT, and CNS-LS may offer clinicians valid tools to detect frontotemporal changes in the ALS population. Development of telephone-based cognitive testing for ALS could become an integral resource for population-based research in the future. PMID:27121545

Telephone based cognitive-behavioral screening for frontotemporal changes in patients with amyotrophic lateral sclerosis (ALS).

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Christodoulou, Georgia; Gennings, Chris; Hupf, Jonathan; Factor-Litvak, Pam; Murphy, Jennifer; Goetz, Raymond R; Mitsumoto, Hiroshi

Our objective was to establish a valid and reliable battery of measures to evaluate frontotemporal dementia (FTD) in patients with ALS over the telephone. Thirty-one subjects were administered either in-person or by telephone-based screening followed by the opposite mode of testing two weeks later, using a modified version of the UCSF Cognitive Screening Battery. Equivalence testing was performed for in-person and telephone based tests. The standard ALS Cognitive Behavioral Screen (ALS-CBS) showed statistical equivalence at the 5% significance level compared to a revised phone version of the ALS-CBS. In addition, the Controlled Oral Word Association Test (COWAT) and Center for Neurologic Study-Lability Scale (CNS-LS) were also found to be equivalent at the 5% and 10% significance level, respectively. Similarly, the Mini-Mental State Examination (MMSE) and the well-established Telephone Interview for Cognitive Status (TICS) were also statistically equivalent. Equivalence could not be claimed for the ALS-Frontal Behavioral Inventory (ALS-FBI) caregiver interview and the Written Verbal Fluency Index (WVFI). In conclusion, our study suggests that telephone-based versions of the ALS-CBS, COWAT, and CNS-LS may offer clinicians valid tools to detect frontotemporal changes in the ALS population. Development of telephone based cognitive testing for ALS could become an integral resource for population based research in the future.

Atrophy in distinct corticolimbic networks in frontotemporal dementia relates to social impairments measured using the Social Impairment Rating Scale

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Bickart, Kevin C; Brickhouse, Michael; Negreira, Alyson; Sapolsky, Daisy

2015-01-01

Patients with frontotemporal dementia (FTD) often exhibit prominent, early and progressive impairments in social behaviour. We developed the Social Impairment Rating Scale (SIRS), rated by a clinician after a structured interview, which grades the types and severity of social behavioural symptoms in seven domains. In 20 FTD patients, we used the SIRS to study the anatomic basis of social impairments. In support of hypotheses generated from a prior study of healthy adults, we found that the relative magnitude of brain atrophy in three partially dissociable corticolimbic networks anchored in the amygdala predicted the severity of distinct social impairments measured using the SIRS. Patients with the greatest atrophy in a mesolimbic, reward-related (affiliation) network exhibited the most severe socioemotional detachment, whereas patients with the greatest atrophy in an interoceptive, pain-related (aversion) network exhibited the most severe lack of social apprehension. Patients with the greatest atrophy in a perceptual network exhibited the most severe lack of awareness or understanding of others’ social and emotional behaviour. Our findings underscore observations that FTD is associated with heterogeneous social symptoms that can be understood in a refined manner by measuring impairments in component processes subserved by dissociable neural networks. Furthermore, these findings support the validity of the SIRS as an instrument to measure the social symptoms of patients with FTD. Ultimately, we hope it will be useful as a longitudinal outcome measure in natural history studies and in clinical trials of putative interventions to improve social functioning. PMID:24133285

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

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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.

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

International Nuclear Information System (INIS)

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

2009-01-01

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 (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.

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 (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.

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.

Transcranial magnetic stimulation in patients with early cortical dementia: A pilot study.

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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.

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

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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.

Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease

NARCIS (Netherlands)

Pottier, C.; Bieniek, K.F.; Finch, N.; Vorst, M. van de; Baker, M.; Perkersen, R.; Brown, P.; Ravenscroft, T.; Blitterswijk, M. van; Nicholson, A.M.; DeTure, M.; Knopman, D.S.; Josephs, K.A.; Parisi, J.E.; Petersen, R.C.; Boylan, K.B.; Boeve, B.F.; Graff-Radford, N.R.; Veltman, J.A.; Gilissen, C.; Murray, M.E.; Dickson, D.W.; Rademakers, R.

2015-01-01

Frontotemporal lobar degeneration with TAR DNA-binding protein 43 inclusions (FTLD-TDP) is the most common pathology associated with frontotemporal dementia (FTD). Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) and mutations in progranulin (GRN) are the major known genetic causes

Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice.

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Filiano, Anthony J; Martens, Lauren Herl; Young, Allen H; Warmus, Brian A; Zhou, Ping; Diaz-Ramirez, Grisell; Jiao, Jian; Zhang, Zhijun; Huang, Eric J; Gao, Fen-Biao; Farese, Robert V; Roberson, Erik D

2013-03-20

Frontotemporal dementia (FTD) is a neurodegenerative disease with hallmark deficits in social and emotional function. Heterozygous loss-of-function mutations in GRN, the progranulin gene, are a common genetic cause of the disorder, but the mechanisms by which progranulin haploinsufficiency causes neuronal dysfunction in FTD are unclear. Homozygous progranulin knock-out (Grn(-/-)) mice have been studied as a model of this disorder and show behavioral deficits and a neuroinflammatory phenotype with robust microglial activation. However, homozygous GRN mutations causing complete progranulin deficiency were recently shown to cause a different neurological disorder, neuronal ceroid lipofuscinosis, suggesting that the total absence of progranulin may have effects distinct from those of haploinsufficiency. Here, we studied progranulin heterozygous (Grn(+/-)) mice, which model progranulin haploinsufficiency. We found that Grn(+/-) mice developed age-dependent social and emotional deficits potentially relevant to FTD. However, unlike Grn(-/-) mice, behavioral deficits in Grn(+/-) mice occurred in the absence of gliosis or increased expression of tumor necrosis factor-α. Instead, we found neuronal abnormalities in the amygdala, an area of selective vulnerability in FTD, in Grn(+/-) mice. Our findings indicate that FTD-related deficits resulting from progranulin haploinsufficiency can develop in the absence of detectable gliosis and neuroinflammation, thereby dissociating microglial activation from functional deficits and suggesting an important effect of progranulin deficiency on neurons.

Longitudinal Diffusion Tensor Imaging Resembles Patterns of Pathology Progression in Behavioral Variant Frontotemporal Dementia (bvFTD

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Jan Kassubek

2018-03-01

Full Text Available Objective: Recently, the characteristic longitudinal distribution pattern of the underlying phosphorylated TDP-43 (pTDP-43 pathology in the behavioral variant of frontotemporal dementia (bvFTD excluding Pick's disease (PiD across specific brain regions was described. The aim of the present study was to investigate whether in vivo investigations of bvFTD patients by use of diffusion tensor imaging (DTI were consistent with these proposed patterns of progression.Methods: Sixty-two bvFTD patients and 47 controls underwent DTI in a multicenter study design. Of these, 49 bvFTD patients and 34 controls had a follow-up scan after ~12 months. Cross-sectional and longitudinal alterations were assessed by a two-fold analysis, i.e., voxelwise comparison of fractional anisotropy (FA maps and a tract of interest-based (TOI approach, which identifies tract structures that could be assigned to brain regions associated with disease progression.Results: Whole brain-based spatial statistics showed white matter alterations predominantly in the frontal lobes cross-sectionally and longitudinally. The TOIs of bvFTD neuroimaging stages 1 and 2 (uncinate fascicle—bvFTD pattern I; corticostriatal pathway—bvFTD pattern II showed highly significant differences between bvFTD patients and controls. The corticospinal tract-associated TOI (bvFTD pattern III did not differ between groups, whereas the differences in the optic radiation (bvFTD pattern IV reached significance. The findings in the corticospinal tract were due to a “dichotomous” behavior of FA changes there.Conclusion: Longitudinal TOI analysis demonstrated a pattern of white matter pathways alterations consistent with patterns of pTDP-43 pathology.

Longitudinal patterns of semantic and episodic memory in frontotemporal lobar degeneration and Alzheimer's disease.

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Xie, Sharon X; Libon, David J; Wang, Xingmei; Massimo, Lauren; Moore, Peachie; Vesely, Luisa; Khan, Alea; Chatterjee, Anjan; Coslett, H Branch; Hurtig, Howard I; Liang, Tsao-Wei; Grossman, Murray

2010-03-01

The longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer's disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype.

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

Differential diagnosis of degenerative dementias using basic neuropsychological tests: multivariable logistic regression analysis of 301 patients.

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Jiménez-Huete, Adolfo; Riva, Elena; Toledano, Rafael; Campo, Pablo; Esteban, Jesús; Barrio, Antonio Del; Franch, Oriol

2014-12-01

The validity of neuropsychological tests for the differential diagnosis of degenerative dementias may depend on the clinical context. We constructed a series of logistic models taking into account this factor. We retrospectively analyzed the demographic and neuropsychological data of 301 patients with probable Alzheimer's disease (AD), frontotemporal degeneration (FTLD), or dementia with Lewy bodies (DLB). Nine models were constructed taking into account the diagnostic question (eg, AD vs DLB) and subpopulation (incident vs prevalent). The AD versus DLB model for all patients, including memory recovery and phonological fluency, was highly accurate (area under the curve = 0.919, sensitivity = 90%, and specificity = 80%). The results were comparable in incident and prevalent cases. The FTLD versus AD and DLB versus FTLD models were both inaccurate. The models constructed from basic neuropsychological variables allowed an accurate differential diagnosis of AD versus DLB but not of FTLD versus AD or DLB. © The Author(s) 2014.

Combined Socio-Behavioral Evaluation Improves the Differential Diagnosis Between the Behavioral Variant of Frontotemporal Dementia and Alzheimer's Disease: In Search of Neuropsychological Markers.

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Dodich, Alessandra; Cerami, Chiara; Cappa, Stefano F; Marcone, Alessandra; Golzi, Valeria; Zamboni, Michele; Giusti, Maria Cristina; Iannaccone, Sandro

2018-01-01

Current diagnostic criteria for behavioral variant of frontotemporal dementia (bvFTD) and typical Alzheimer's disease (AD) include a differential pattern of neuropsychological impairments (episodic memory deficit in typical AD and dysexecutive syndrome in bvFTD). There is, however, large evidence of a frequent overlap in neuropsychological features, making the differential diagnosis extremely difficult. In this retrospective study, we evaluated the diagnostic value of different cognitive and neurobehavioral markers in bvFTD and AD patient groups. We included 95 dementia patients with a clinical and biomarker evidence of bvFTD (n = 48) or typical AD (n = 47) pathology. A clinical 2-year follow-up confirmed clinical classification. Performances at basic cognitive tasks (memory, executive functions, visuo-spatial, language) as well as social cognition skills and neurobehavioral profiles have been recorded. A stepwise logistic regression model compared the neuropsychological profiles between groups and assessed the accuracy of cognitive and neurobehavioral markers in discriminating bvFTD from AD. Statistical comparison between patient groups proved social cognition and episodic memory impairments as main cognitive signatures of bvFTD and AD neuropsychological profiles, respectively. Only half of bvFTD patients showed attentive/executive deficits, questioning their role as cognitive marker of bvFTD. Notably, the large majority of bvFTD sample (i.e., 70%) poorly performed at delayed recall tasks. Logistic regression analysis identified social cognition performances, Frontal Behavioral Inventory and Mini-Mental State Examination scores as the best combination in distinguishing bvFTD from AD. Social cognition tasks and socio-behavioral questionnaires are recommended in clinical settings to improve the accuracy of early diagnosis of bvFTD.

Opening up the DNA methylome of dementia.

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Delgado-Morales, R; Esteller, M

2017-04-01

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.

The Mini-Addenbrooke's Cognitive Examination: a new assessment tool for dementia.

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Hsieh, Sharpley; McGrory, Sarah; Leslie, Felicity; Dawson, Kate; Ahmed, Samrah; Butler, Chris R; Rowe, James B; Mioshi, Eneida; Hodges, John R

2015-01-01

We developed and validated the Mini-Addenbrooke's Cognitive Examination (M-ACE) in dementia patients. Comparisons were also made with the Mini Mental State Examination (MMSE). The M-ACE was developed using Mokken scaling analysis in 117 dementia patients [behavioural variant frontotemporal dementia (bvFTD), n = 25; primary progressive aphasia (PPA), n = 49; Alzheimer's disease (AD), n = 34; corticobasal syndrome (CBS), n = 9] and validated in an independent sample of 164 dementia patients (bvFTD, n = 23; PPA, n = 82; AD, n = 38; CBS, n = 21) and 78 controls, who also completed the MMSE. The M-ACE consists of 5 items with a maximum score of 30. Two cut-offs were identified: (1) ≤25/30 has both high sensitivity and specificity, and (2) ≤21/30 is almost certainly a score to have come from a dementia patient regardless of the clinical setting. The M-ACE is more sensitive than the MMSE and is less likely to have ceiling effects. The M-ACE is a brief and sensitive cognitive screening tool for dementia. Two cut-offs (25 or 21) are recommended. © 2014 S. Karger AG, Basel.

[Investigation of Genetic Etiology in Neurodegenerative Dementias: Recommendations from the Centro Hospitalar São João Neurogenetics Group].

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Massano, João; Leão, Miguel; Garrett, Carolina

2016-10-01

In the past few years several gene mutations have been identified as causative of the most frequent neurodegenerative dementias (Alzheimer disease and frontotemporal dementia). These advances, along with the complex phenotype-genotype relationships and the costs associated with genetic testing, have often made it difficult for clinicians to decide with regard to a rational plan for the investigation of the genetic etiology of the degenerative dementias. The Centro Hospitalar São João Neurogenetics Group, a multidisciplinary team of Neurologists and Geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic etiology of Alzheimer disease and frontotemporal dementia in clinical practice, based on international consensus documents (currently containing partly outdated information) and published scientific evidence on this topic. Alzheimer disease may be caused by mutations in PSEN1, PSEN2 and APP. APOE genotyping is not recommended for the diagnostic or genetic counseling purposes in Alzheimer disease. Frontotemporal dementia may be caused by mutations in several genes such as c9orf72, PGRN, MAPT, TBK1, VCP, SQSTM1, and UBQLN2. This paper pragmatically approaches the process of genetic diagnosis in Alzheimer disease and frontotemporal dementia, with specific recommendations for both disorders.

TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)

DEFF Research Database (Denmark)

Rostgaard, Nina; Roos, Peter; Budtz-Jørgensen, Esben

2017-01-01

(ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset......Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E...... factor with later AAO and AAI, whereas ε2 seemed to aggravate the disease with earlier AAO and AAD. These results indicate ApoE ε2 as a risk factor in FTD-3 and suggest a protective role of ε4....

[Reconciliating neurology and psychiatry: The prototypical case of frontotemporal dementia].

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Lagarde, J; Sarazin, M

2017-10-01

Frontotemporal degeneration (FTD) in its behavioral variant (bvFTD) is probably one of the conditions that best illustrates the links between psychiatry and neurology. It is indeed admitted that between a third and half of patients with this condition, especially in early-onset forms, receive an initial diagnosis of psychiatric disorder (depression, schizophrenia, bipolar disorder) and are then referred to a psychiatric ward. BvFTD can thus be considered a neurological disorder with a psychiatric presentation. Among psychiatric symptoms reported in this disease, psychotic symptoms (hallucinations, delusions, especially of persecution), which have long been underestimated in bvFTD and are not part of the current diagnostic criteria, are present in about 20% of cases and may be inaugural. They are particularly common in the genetic forms related to a mutation in the C9orf72 gene (up to 50%), and to a lesser extent in the GRN gene (up to 25%). C9orf72 gene mutation is often associated with a family history of dementia or motor neuron disease but also of psychiatric disorders. It has also been described in sporadic presentation forms. Sometimes, the moderate degree of brain atrophy on MRI described in patients carrying this mutation may complicate the differential diagnosis with late-onset psychiatric diseases. In the present article, we underline the importance of considering that psychiatric - especially psychotic - symptoms are not rare in bvFTD, which should lead to a revision of the diagnostic criteria of this disease by taking greater account of this fact. We also propose a diagnostic chart, based on concerted evaluation by neurologists and psychiatrists for cases of atypical psychiatric symptoms (late-onset or pharmacoresistant troubles) leading to consider the possibility of a neurological disorder, in order to shed a new light on these difficult clinical situations. In the field of research, bvFTD may constitute a model to explore the neural basis of certain

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy: effects of genetic, demographic and neuropathological variables

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Richard A. Armstrong

2016-06-01

Full Text Available Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD with transactive response (TAR DNA-binding protein of 43 kDa (TDP-43 proteinopathy (FTLD-TDP. Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64. Familial and sporadic cases exhibited similar survival, including progranulin (GRN gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND but increased with Alzheimer’s disease (AD or hippocampal sclerosis (HS co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI while increased survival was associated with greater densities of enlarged neurons (EN in the frontal and temporal lobes. The data suggest that: (1 survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA, (2 MND co-morbidity predicts poor survival, and (3 NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.

Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia.

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Dols-Icardo, Oriol; García-Redondo, Alberto; Rojas-García, Ricard; Sánchez-Valle, Raquel; Noguera, Aina; Gómez-Tortosa, Estrella; Pastor, Pau; Hernández, Isabel; Esteban-Pérez, Jesús; Suárez-Calvet, Marc; Antón-Aguirre, Sofía; Amer, Guillermo; Ortega-Cubero, Sara; Blesa, Rafael; Fortea, Juan; Alcolea, Daniel; Capdevila, Aura; Antonell, Anna; Lladó, Albert; Muñoz-Blanco, José Luís; Mora, Jesús S; Galán-Dávila, Lucía; Rodríguez De Rivera, Francisco Javier; Lleó, Alberto; Clarimón, Jordi

2014-02-01

Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotide repeat number and clinical phenotype. Here we characterize, through a new non-radioactive Southern blot protocol, the expansion size range in a series of 38 ALS and 22 FTD heterozygous carriers of >30 copies of the repeat. Maximum, median and modal hexanucleotide repeat number were higher in ALS patients than in FTD patients (P< 0.05 in all comparisons). A higher median number of repeats correlated with a bigger range of repeat sizes (Spearman's ρ = 0.743, P = 1.05 × 10(-11)). We did not find any correlation between age of onset or disease duration with the repeat size in neither ALS nor FTD mutation carriers. Clinical presentation (bulbar or spinal) in ALS patients did not correlate either with the repeat length. We finally analyzed two families with affected and unaffected repeat expansion carriers, compared the size of the repeat expansion between two monozygotic (MZ) twins (one affected of ALS and the other unaffected), and examined the expansion size in two different tissues (cerebellum and peripheral blood) belonging to the same FTD patient. The results suggested that the length of the C9orf72 repeat varies between family members, including MZ twins, and among different tissues from the same individual.

Transcranial magnetic stimulation in patients with early cortical dementia: A pilot study

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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.

Use of antidementia drugs in frontotemporal lobar degeneration.

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López-Pousa, Secundino; Calvó-Perxas, Laia; Lejarreta, Saioa; Cullell, Marta; Meléndez, Rosa; Hernández, Erélido; Bisbe, Josep; Perkal, Héctor; Manzano, Anna; Roig, Anna Maria; Turró-Garriga, Oriol; Vilalta-Franch, Joan; Garre-Olmo, Josep

2012-06-01

Clinical evidence indicates that acetylcholinesterase inhibitors (AChEIs) are not efficacious to treat frontotemporal lobar degeneration (FTLD). The British Association for Psychopharmacology recommends avoiding the use of AChEI and memantine in patients with FTLD. Cross-sectional design using 1092 cases with Alzheimer's disease (AD) and 64 cases with FTLD registered by the Registry of Dementias of Girona. Bivariate analyses were performed, and binary logistic regressions were used to detect variables associated with antidementia drugs consumption. The AChEIs were consumed by 57.6% and 42.2% of the patients with AD and FTLD, respectively. Memantine was used by 17.2% and 10.9% of patients with AD and FTLD, respectively. Binary logistic regressions yielded no associations with antidementia drugs consumption. There is a discrepancy regarding clinical practice and the recommendations based upon clinical evidence. The increased central nervous system drug use detected in FTLD requires multicentric studies aiming at finding the best means to treat these patients.

Progranulin, a glycoprotein deficient in frontotemporal dementia, is a novel substrate of several protein disulfide isomerase family proteins.

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Sandra Almeida

Full Text Available The reduced production or activity of the cysteine-rich glycoprotein progranulin is responsible for about 20% of cases of familial frontotemporal dementia. However, little is known about the molecular mechanisms that govern the level and secretion of progranulin. Here we show that progranulin is expressed in mouse cortical neurons and more prominently in mouse microglia in culture and is abundant in the endoplasmic reticulum (ER and Golgi. Using chemical crosslinking, immunoprecipitation, and mass spectrometry, we found that progranulin is bound to a network of ER Ca(2+-binding chaperones including BiP, calreticulin, GRP94, and four members of the protein disulfide isomerase (PDI family. Loss of ERp57 inhibits progranulin secretion. Thus, progranulin is a novel substrate of several PDI family proteins and modulation of the ER chaperone network may be a therapeutic target for controlling progranulin secretion.

Behavioral and autonomic reactivity to moral dilemmas in frontotemporal dementia versus Alzheimer's disease.

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Fong, Sylvia S; Navarrete, Carlos David; Perfecto, Sean E; Carr, Andrew R; Jimenez, Elvira E; Mendez, Mario F

2017-08-01

The personal/impersonal distinction of moral decision-making postulates intuitive emotional responses from medial frontal activity and rational evaluation from lateral frontal activity. This model can be analyzed in behavioral variant frontotemporal dementia (bvFTD), a disorder characterized by impaired emotional intuitions, ventromedial prefrontal cortex (vmPFC) involvement, and relative sparing of lateral frontal regions. Moral dilemmas were presented to 10 bvFTD, 11 Alzheimer's disease (AD), and 9 healthy control (HC) participants while recording skin conductance responses, a measure of emotional arousal. We evaluated their personal versus impersonal conflict, subjective discomfort, and adherence to social norms. Replicating prior work, bvFTD participants were more willing to harm in the personal, but not the impersonal, dilemma compared to AD and HC groups. BvFTD participants had lower arousal and less of an increase in conflict on the personal versus the impersonal dilemma, in contrast to increased arousal and conflict for the AD and HC groups. Furthermore, bvFTD participants verbalized less discomfort, a correlate of low adherence to social norms. These findings support impaired emotional reactions to moral dilemmas in bvFTD and vmPFC lesions and the personal/impersonal model. It suggests a reversion to utilitarian-like considerations when emotional intuition is impaired in the brain.

Bipolar disorder and dementia: where is the link?

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Masouy, Anaïs; Chopard, Gilles; Vandel, Pierre; Magnin, Eloi; Rumbach, Lucien; Sechter, Daniel; Haffen, Emmanuel

2011-03-01

Cognitive disorders appearing in the course of bipolar disease have been identified, and recent studies have defined the neuropsychological characteristics of this pathology, which includes attention, executive function, memory and language disorders. However, questions remain concerning the appearance of dementia symptoms over the course of bipolar disorder in certain patients: is it a chance association or is there a connection between bipolar disorders and dementia? If the latter hypothesis is considered, what is the nature of the dementia, which might be considered as a dementia specific to bipolar disorder? Current clinical, neuropsychological and cerebral imaging data are inconclusive, but similarities with frontotemporal dementia might be highlighted. Functional imaging studies might provide answers as well as more specific tests in neuropsychology. The cause of cognitive damage in bipolar disease also raises questions concerning a neurodevelopmental or neurodegenerative process, because several factors seem to influence cognition and these two processes might occur simultaneously. Long-term studies are necessary to determine whether cognitive deterioration in bipolar disease is stable or progressive. There might also be different neurobiological subgroups of patients with bipolar disease. © 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.

Comparing the driving behaviours of individuals with frontotemporal lobar degeneration and those with Alzheimer's disease.

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Fujito, Ryoko; Kamimura, Naoto; Ikeda, Manabu; Koyama, Asuka; Shimodera, Shinji; Morinobu, Shigeru; Inoue, Shimpei

2016-01-01

Assessing driving aptitude in dementia patients is critically important for both patient and public safety. However, there have been only a few reports on the driving behaviours and accident risk of patients with dementia, especially frontotemporal lobar degeneration (FTLD). Therefore, we compared the characteristics of driving behaviours in patients with FTLD and those with Alzheimer's disease (AD). The subjects were 28 FTLD and 67 AD patients who visited the Department of Psychiatry, Kochi Medical School Hospital. We conducted semi-structured interviews with their families and caregivers about traffic accident history and changes in patient driving behaviours after dementia onset and then compared the findings between the two groups. Overall changes in driving behaviours were reported in 89% (25/28) and 76% (51/67) of the FTLD and AD patients, respectively (P = 0.17). In the FTLD group, difficulty in judging inter-vehicle distances, ignoring road signs and traffic signals, and distraction were reported in 50% (14/28), 61% (17/28), and 50% (14/28) of patients, respectively, and 75% (21/28) patients had caused a traffic accident after dementia onset. The risk of causing an accident was higher in the FTLD group than in the AD group (odds ratio = 10.4, 95% confidence interval = 3.7-29.1). In addition, the mean duration between dementia onset and a traffic accident was 1.35 years in the FTLD group compared with 3.0 years in the AD group (P driving behaviours than those with AD, and the risk of causing a traffic accident may be higher in patients with FTLD from an early disease stage. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

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.)

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

International Nuclear Information System (INIS)

Verfaillie, Sander C.J.; Adriaanse, Sofie M.; Binnewijzend, Maja A.A.; Benedictus, Marije R.; Ossenkoppele, Rik; Wattjes, Mike P.; Lammertsma, Adriaan A.; Boellaard, Ronald; Berckel, Bart N.M. van; Barkhof, Frederik; Pijnenburg, Yolande A.L.; Scheltens, Philip; Flier, Wiesje M. van der; Kuijer, Joost P.A.

2015-01-01

Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [ 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.)

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

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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

[Spontaneous speech prosody and discourse analysis in schizophrenia and Fronto Temporal Dementia (FTD) patients].

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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.

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

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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. Copyright 2014, SLACK Incorporated.

MR spectroscopy in dementia; MR-Spektroskopie bei Demenz

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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.)

[Self-consciousness, consciousness of the other and dementias].

Science.gov (United States)

Gil, Roger

2007-06-01

Studies of self-consciousness in dementia concern essentially anosognosia or the loss of insight. However, Self-consciousness is multifaceted: it includes awareness of the body, perceptions, one's own history, identity, and one's own projects. Self-consciousness is linked to consciousness of others i.e. to social cognition supported by identification of others, but also by comprehension of facial expression of emotions, comprehension and expression of emotional prosody, pragmatic abilities, ability to infer other's people's mental states, thoughts, and feelings (theory of mind and empathy), knowledge of social norms and rules, social reasoning. The subtypes of dementias (and namely Alzheimer's disease and frontotemporal dementia) affect heterogeneously the different aspects of the self-and other-consciousness. Further studies are needed for a better knowledge of the complex relationship between Self-consciousness, social cognition, decision making and neuropsychiatric symptoms and behavioral disturbances occurring in demented patients.

A correlation of clinical, MRI and brain SPECT in dementia

International Nuclear Information System (INIS)

Shelley, S.; Indirani, M.; Gokhale, S.; Anirudhan, N.; Sivakumar, M.R.; Jaganathan, K.

2004-01-01

Background: Dementia is a clinical syndrome characterised by acquired impairment in multiple neuropsycologic and behavior domains including memory, language, speech, visuospatial ability, cognition and mood/personality. Dementia produces deficits in perfusion reflecting decreased metabolic needs. Neuroimaging techniques help in determining whether the cognitive symptoms are organic and in which pattern of cognitive loss the patient may evolve. AIM: To differentiate various types of Dementia, based on the regional perfusion abnormalities seen in Brain SPECT and correlate this with Clinical and MRI findings. Material and methods: Patients suffering from memory impairment and memory loss were referred to our department for Brain SPECT as a part of work up for Dementia. They had undergone a detailed clinical examination, psychometry, mini mental status examination (MMSE), memory/cognitive testing and an MRI. Brain SPECT was done after injecting Tc 99m ECD (Ethylene Cysteinate Dimer ) and imaging after 45 minutes. The images obtained were reconstructed in a conventional way. The various patterns of perfusion abnormalities seen in the SPECT images was studied and correlated with MRI and clinical findings. The patients were thus classified as having Multi Infarct Dementia, Alzheimer's disease, Fronto-Temporal Dementia and Mixed variety. Results: Twenty One Patients were included in our study from February 2003 to February 2004. The mean age of the patients was 73 years ( 37 to 81). 15 were males and 6 were females. Out of 21 patients, 12 had Multi Infarct Dementia, 4 had Alzheimer's disease, 1 had Fronto- Temporal Dementia and 4 had Mixed variety. Conclusion: Brain SPECT aids in substantiating the clinical findings and in correlation with MRI helps in distinguishing various types of Dementia and thus has prognostic implications and helps in instituting early appropriate treatment to the patient. In our study, the majority of the patients have Multi Infarct Dementia

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

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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.)

Problems of Face Recognition in Patients with Behavioral Variant Frontotemporal Dementia.

Science.gov (United States)

Chandra, Sadanandavalli Retnaswami; Patwardhan, Ketaki; Pai, Anupama Ramakanth

2017-01-01

Faces are very special as they are most essential for social cognition in humans. It is partly understood that face processing in its abstractness involves several extra striate areas. One of the most important causes for caregiver suffering in patients with anterior dementia is lack of empathy. This apart from being a behavioral disorder could be also due to failure to categorize the emotions of the people around them. Inlusion criteria: DSM IV for Bv FTD Tested for prosopagnosia - familiar faces, famous face, smiling face, crying face and reflected face using a simple picture card (figure 1). Advanced illness and mixed causes. 46 patients (15 females, 31 males) 24 had defective face recognition. (mean age 51.5),10/15 females (70%) and 14/31males(47. Familiar face recognition defect was found in 6/10 females and 6/14 males. Total- 40%(6/15) females and 19.35%(6/31)males with FTD had familiar face recognition. Famous Face: 9/10 females and 7/14 males. Total- 60% (9/15) females with FTD had famous face recognition defect as against 22.6%(7/31) males with FTD Smiling face defects in 8/10 female and no males. Total- 53.33% (8/15) females. Crying face recognition defect in 3/10 female and 2 /14 males. Total- 20%(3/15) females and 6.5%(2/31) males. Reflected face recognition defect in 4 females. Famous face recognition and positive emotion recognition defect in 80%, only 20% comprehend positive emotions, Face recognition defects are found in only 45% of males and more common in females. Face recognition is more affected in females with FTD There is differential involvement of different aspects of the face recognition could be one of the important factor underlying decline in the emotional and social behavior of these patients. Understanding these pathological processes will give more insight regarding patient behavior.

Bilingualism delays age at onset of dementia, independent of education and immigration status.

Science.gov (United States)

Alladi, Suvarna; Bak, Thomas H; Duggirala, Vasanta; Surampudi, Bapiraju; Shailaja, Mekala; Shukla, Anuj Kumar; Chaudhuri, Jaydip Ray; Kaul, Subhash

2013-11-26

The purpose of the study was to determine the association between bilingualism and age at onset of dementia and its subtypes, taking into account potential confounding factors. Case records of 648 patients with dementia (391 of them bilingual) diagnosed in a specialist clinic were reviewed. The age at onset of first symptoms was compared between monolingual and bilingual groups. The influence of number of languages spoken, education, occupation, and other potentially interacting variables was examined. Overall, bilingual patients developed dementia 4.5 years later than the monolingual ones. A significant difference in age at onset was found across Alzheimer disease dementia as well as frontotemporal dementia and vascular dementia, and was also observed in illiterate patients. There was no additional benefit to speaking more than 2 languages. The bilingual effect on age at dementia onset was shown independently of other potential confounding factors such as education, sex, occupation, and urban vs rural dwelling of subjects. This is the largest study so far documenting a delayed onset of dementia in bilingual patients and the first one to show it separately in different dementia subtypes. It is the first study reporting a bilingual advantage in those who are illiterate, suggesting that education is not a sufficient explanation for the observed difference. The findings are interpreted in the context of the bilingual advantages in attention and executive functions.

Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis.

Science.gov (United States)

Arrant, Andrew E; Onyilo, Vincent C; Unger, Daniel E; Roberson, Erik D

2018-02-28

Loss-of-function mutations in progranulin, a lysosomal glycoprotein, cause neurodegenerative disease. Progranulin haploinsufficiency causes frontotemporal dementia (FTD) and complete progranulin deficiency causes CLN11 neuronal ceroid lipofuscinosis (NCL). Progranulin replacement is a rational therapeutic strategy for these disorders, but there are critical unresolved mechanistic questions about a progranulin gene therapy approach, including its potential to reverse existing pathology. Here, we address these issues using an AAV vector (AAV- Grn ) to deliver progranulin in Grn -/- mice (both male and female), which model aspects of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and microgliosis. We first tested whether AAV- Grn could improve preexisting pathology. Even with treatment after onset of pathology, AAV- Grn reduced lipofuscinosis in several brain regions of Grn -/- mice. AAV- Grn also reduced microgliosis in brain regions distant from the injection site. AAV-expressed progranulin was only detected in neurons, not in microglia, indicating that the microglial activation in progranulin deficiency can be improved by targeting neurons and thus may be driven at least in part by neuronal dysfunction. Even areas with sparse transduction and almost undetectable progranulin showed improvement, indicating that low-level replacement may be sufficiently effective. The beneficial effects of AAV- Grn did not require progranulin binding to sortilin. Finally, we tested whether AAV- Grn improved lysosomal function. AAV-derived progranulin was delivered to the lysosome, ameliorated the accumulation of LAMP-1 in Grn -/- mice, and corrected abnormal cathepsin D activity. These data shed light on progranulin biology and support progranulin-boosting therapies for NCL and FTD due to GRN mutations. SIGNIFICANCE STATEMENT Heterozygous loss-of-function progranulin ( GRN ) mutations cause frontotemporal dementia (FTD) and homozygous mutations cause neuronal

Neuropsychological assessment and differential diagnosis in young-onset dementias.

Science.gov (United States)

Sitek, Emilia J; Barczak, Anna; Harciarek, Michał

2015-06-01

Although Alzheimer's disease is the most common cause of dementia in the elderly, there are several conditions (ie, frontotemporal dementia or Huntington's disease) associated with a relatively earlier onset. This article provides arguments in favor of a comprehensive neuropsychological assessment in the differential diagnosis of young-onset dementia, as episodic memory impairment is not observed early in the course of most types of young-onset dementia that predominantly affect the domains of behavior, executive, language, and/or motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Car drivers with dementia: Different complications due to different etiologies?

Science.gov (United States)

Piersma, Dafne; de Waard, Dick; Davidse, Ragnhild; Tucha, Oliver; Brouwer, Wiebo

2016-01-01

Older drivers with dementia are an at-risk group for unsafe driving. However, dementia refers to various etiologies and the question is whether dementias of different etiology have similar effects on driving ability. The literature on the effects of dementia of various etiologies on driving ability is reviewed. Studies addressing dementia etiologies and driving were identified through PubMed, PsychINFO, and Google Scholar. Early symptoms and prognoses differ between dementias of different etiology. Therefore, different etiologies may represent different likelihoods with regard to fitness to drive. Moreover, dementia etiologies could indicate the type of driving problems that can be expected to occur. However, there is a great lack of data and knowledge about the effects of almost all etiologies of dementia on driving. One could hypothesize that patients with Alzheimer's disease may well suffer from strategic difficulties such as finding a route, whereas patients with frontotemporal dementia are more inclined to make tactical-level errors because of impaired hazard perception. Patients with other dementia etiologies involving motor symptoms may suffer from problems on the operational level. Still, the effects of various etiologies of dementias on driving have thus far not been studied thoroughly. For the detection of driving difficulties in patients with dementia, structured interviews with patients but also their family members appear crucial. Neuropsychological assessment could support the identification of cognitive impairments. The impact of such impairments on driving could also be investigated in a driving simulator. In a driving simulator, strengths and weaknesses in driving behavior can be observed. With this knowledge, patients can be advised appropriately about their fitness to drive and options for support in driving (e.g., compensation techniques, car adaptations). However, as long as no valid, reliable, and widely accepted test battery is available for

Social Cognition Deficits: The Key to Discriminate Behavioral Variant Frontotemporal Dementia from Alzheimer's Disease Regardless of Amnesia?

Science.gov (United States)

Bertoux, Maxime; de Souza, Leonardo Cruz; O'Callaghan, Claire; Greve, Andrea; Sarazin, Marie; Dubois, Bruno; Hornberger, Michael

2016-01-01

Relative sparing of episodic memory is a diagnostic criterion of behavioral variant frontotemporal dementia (bvFTD). However, increasing evidence suggests that bvFTD patients can show episodic memory deficits at a similar level as Alzheimer's disease (AD). Social cognition tasks have been proposed to distinguish bvFTD, but no study to date has explored the utility of such tasks for the diagnosis of amnestic bvFTD. Here, we contrasted social cognition performance of amnestic and non-amnestic bvFTD from AD, with a subgroup having confirmed in vivo pathology markers. Ninety-six participants (38 bvFTD and 28 AD patients as well as 30 controls) performed the short Social-cognition and Emotional Assessment (mini-SEA). BvFTD patients were divided into amnestic versus non-amnestic presentation using the validated Free and Cued Selective Reminding Test (FCSRT) assessing episodic memory. As expected, the accuracy of the FCSRT to distinguish the overall bvFTD group from AD was low (69.7% ) with ∼50% of bvFTD patients being amnestic. By contrast, the diagnostic accuracy of the mini-SEA was high (87.9% ). When bvFTD patients were split on the level of amnesia, mini-SEA diagnostic accuracy remained high (85.1% ) for amnestic bvFTD versus AD and increased to very high (93.9% ) for non-amnestic bvFTD versus AD. Social cognition deficits can distinguish bvFTD and AD regardless of amnesia to a high degree and provide a simple way to distinguish both diseases at presentation. These findings have clear implications for the diagnostic criteria of bvFTD. They suggest that the emphasis should be on social cognition deficits with episodic memory deficits not being a helpful diagnostic criterion in bvFTD.

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.

FDG PET imaging dementia

International Nuclear Information System (INIS)

Ahn, Byeong Cheol

2007-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Bron, Esther E.; Klein, Stefan [Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology and Nuclear Medicine, Office Na2502, P.O. Box 2040, Rotterdam (Netherlands); Smits, Marion; Steketee, Rebecca M.E.; Meijboom, Rozanna [Erasmus MC, Department of Radiology and Nuclear Medicine, Rotterdam (Netherlands); Papma, Janne M.; Swieten, John C. van [Erasmus MC, Department of Neurology, Rotterdam (Netherlands); Groot, Marius de [Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology and Nuclear Medicine, Office Na2502, P.O. Box 2040, Rotterdam (Netherlands); Erasmus MC, Department of Epidemiology, Rotterdam (Netherlands); Niessen, Wiro J. [Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology and Nuclear Medicine, Office Na2502, P.O. Box 2040, Rotterdam (Netherlands); Delft University of Technology, Imaging Physics, Applied Sciences, Delft (Netherlands)

2017-08-15

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. This retrospective study used MRI data from 24 early-onset AD and 33 early-onset FTD patients and 34 controls (CN). Classification was based on voxel-wise feature maps derived from structural MRI, ASL, and DTI. Support vector machines (SVMs) were trained to classify AD versus CN (AD-CN), FTD-CN, AD-FTD, and AD-FTD-CN (multi-class). Classification performance was assessed by the area under the receiver-operating-characteristic curve (AUC) and accuracy. Using SVM significance maps, we analysed contributions of brain regions. Combining ASL and DTI with structural MRI resulted in higher classification performance for differential diagnosis of AD and FTD (AUC = 84%; p = 0.05) than using structural MRI by itself (AUC = 72%). The performance of ASL and DTI themselves did not improve over structural MRI. The classifications were driven by different brain regions for ASL and DTI than for structural MRI, suggesting complementary information. ASL and DTI are promising additions to structural MRI for classification of early-onset AD, early-onset FTD, and controls, and may improve the computer-aided differential diagnosis on a single-subject level. (orig.)

Right Frontotemporal Cortex Mediates the Relationship between Cognitive Insight and Subjective Quality of Life in Patients with Schizophrenia.

Science.gov (United States)

Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Ohtachi, Hiroaki; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

2018-01-01

Although prior studies identified a relationship between cognitive insight and subjective quality of life (QOL) in patients with schizophrenia, the brain regions mediating this relationship remain unknown. Recent studies have shown that the ventrolateral prefrontal cortex may be particularly important for cognitive insight in individuals with schizophrenia. Here, we examined whether frontotemporal function mediates the relationship between cognitive insight and QOL in 64 participants, including 32 patients with schizophrenia and 32 healthy controls. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS), while participants' subjective QOL was assessed using the Medical Outcomes Study 36-item Short-form Health Survey. Frontotemporal function was evaluated during a verbal fluency task using multichannel near-infrared spectroscopy. Consistent with previous findings, we found that frontotemporal function was impaired in patients with schizophrenia. Interestingly, our data also revealed that the right ventrolateral PFC and the right anterior part of the temporal cortex significantly mediated the relationship between the self-reflectiveness (SR) subscale of the BCIS and subjective QOL. These findings suggest that cognitive insight, particularly SR, is associated with subjective QOL in patients with schizophrenia via right frontotemporal function. The findings of this study provide important insight into a QOL model of schizophrenia, which may guide the development of cost-effective interventions that target frontotemporal function in patients with schizophrenia.

Impact of advanced MRI techniques for the diagnosis of dementia: comparison with PET

DEFF Research Database (Denmark)

Steffensen, Elena; Prakash, Vineet; Vestergård, Karsten

Introduction: The use of high magnetic fields in combination with fast algorithms for computer-based postprocessing has moved advanced MRI techniques into clinical practice. MRI provides in analogy with PET physiological information in addition to more traditional morphological images. Evaluation...... with suspected Alzheimer's disease (AD); 4 with suspected frontotemporal dementia (FTD), and 2 were found normal. Mean FA and ADC values in cingulum and in CC for the patient group compared with controls are presented in Table 1. ADC values in CC were higher comparing with controls and higher for patients...... with suspected FTD than for patients with suspected AD. Conclusion: CBF measurements and characteristics obtained by advanced MRI techniques have a potential to facilitate early diagnosis and understanding of dementia....

Dementia Caregiver Burden: a Research Update and Critical Analysis.

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Cheng, Sheung-Tak

2017-08-10

This article provides an updated review of the determinants of caregiver burden and depression, with a focus on care demands and especially the differential effects of various neuropsychiatric symptoms or symptom clusters. Moreover, studies on caregivers for frontotemporal and Lewy body dementias were referred to in order to identify differences and similarities with the mainstream literature based largely on Alzheimer caregivers. As a group, neuropsychiatric symptoms are most predictive of caregiver burden and depression regardless of dementia diagnosis, but the effects appear to be driven primarily by disruptive behaviors (e.g., agitation, aggression, disinhibition), followed by delusions and mood disturbance. Disruptive behaviors are more disturbing partly because of the adverse impact on the emotional connection between the caregiver and the care-recipient and partly because they exacerbate difficulties in other domains (e.g., caring for activities of daily living). In behavioral variant frontotemporal dementia, not only are these disruptive behaviors more prominent but they are also more disturbing due to the care-recipient's insensitivity to others' feelings. In Lewy body dementia, visual hallucinations also appear to be distressing. The disturbing nature of disruptive behaviors cuts across dementia conditions, but the roles played by symptoms that are unique or particularly serious in a certain condition need to be explored further.

Dementia and functional cerebral imaging a reevaluation

International Nuclear Information System (INIS)

Steinling, M.; Lecouffe, P.; Pham, T.; Charpentier, P.; Delebvre, L.; Lavenu, I.; Pasquier, F.; Charpentier, P.; Duhamel, A.

2000-01-01

New concepts which concerned especially the nosologic classification of dementia as for example Dementia with Lewy Bodies (DLB) incite to revalue the main characteristics of the regional cerebral blood flow measurements studied by SPECT in several forms of dementia. SPECT analysis with 99m-Technetium HMPAO (555 MBq) was performed to 20 patients with probable DLB, 20 patients with probable Alzheimer's disease (AD) and 20 patients with Fronto-Temporal dementia (FTD). Ten pairs of regions of interest were analysed. Tracer uptake was expressed as a cortico-cerebellar activity ratio. Statistical analysis of index of fixation was performed using an univariate analysis of variance, and a selection of significative ROIs was performed using two cut-off values (80 and 82.5 %). In the FTD group, a decrease of HMPAO uptake in frontal cortical regions of interest (internal, lateral and posterior) was observed. In the DLB group the decrease of HMPAO uptake was widespread and concerned all the cortical regions of interest except the posterior frontal and occipital regions. Finally in the AD group there was a limited temporal and parietal hypoperfusion more marked on the left side without frontal hypoperfusion. This last result was obtained whatever the cognitive impairment. Consequently it seems that the frontal hypoperfusion previously reported in AD groups was induced by the fact that patients with DLB were also included because the diagnosis was not established. In conclusion we estimate that SPECT studies could be used more often in clinical research especially for a classification approach of dementia. (authors)

Validation of Addenbrooke's cognitive examination for detecting early dementia in a Japanese population.

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Yoshida, Hidenori; Terada, Seishi; Honda, Hajime; Ata, Toshie; Takeda, Naoya; Kishimoto, Yuki; Oshima, Etsuko; Ishihara, Takeshi; Kuroda, Shigetoshi

2011-01-30

There is a clear need for brief, but sensitive and specific, cognitive screening instruments for dementia. We assessed the diagnostic accuracy of the Japanese version of Addenbrooke's Cognitive Examination (ACE) in identifying early dementia in comparison with the conventional Mini-Mental State Examination (MMSE). Standard tests for evaluating dementia screening tests were applied. A total of 201 subjects (Alzheimer's disease (AD)=65, frontotemporal dementia (FTD)=24, vascular dementia=26, dementia with Lewy bodies=11, mild cognitive impairment (MCI)=13, and controls=62) participated in this study. The reliability of the ACE was very good (alpha coefficient=0.82). In our patient series, the sensitivity for diagnosing dementia with an ACE score of ≤74 was 0.889 with a specificity of 0.987, and the sensitivity of an ACE score of ≤80 was 0.984 with a specificity of 0.867. The Japanese version of the ACE is a very accurate instrument for the detection of early dementia, and should be widely used in clinical practice. Copyright © 2009 Elsevier Ltd. All rights reserved.

Poor Gait Performance and Prediction of Dementia: Results From a Meta-Analysis.

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Beauchet, Olivier; Annweiler, Cédric; Callisaya, Michele L; De Cock, Anne-Marie; Helbostad, Jorunn L; Kressig, Reto W; Srikanth, Velandai; Steinmetz, Jean-Paul; Blumen, Helena M; Verghese, Joe; Allali, Gilles

2016-06-01

Poor gait performance predicts risk of developing dementia. No structured critical evaluation has been conducted to study this association yet. The aim of this meta-analysis was to systematically examine the association of poor gait performance with incidence of dementia. An English and French Medline search was conducted in June 2015, with no limit of date, using the medical subject headings terms "Gait" OR "Gait Disorders, Neurologic" OR "Gait Apraxia" OR "Gait Ataxia" AND "Dementia" OR "Frontotemporal Dementia" OR "Dementia, Multi-Infarct" OR "Dementia, Vascular" OR "Alzheimer Disease" OR "Lewy Body Disease" OR "Frontotemporal Dementia With Motor Neuron Disease" (Supplementary Concept). Poor gait performance was defined by standardized tests of walking, and dementia was diagnosed according to international consensus criteria. Four etiologies of dementia were identified: any dementia, Alzheimer disease (AD), vascular dementia (VaD), and non-AD (ie, pooling VaD, mixed dementias, and other dementias). Fixed effects meta-analyses were performed on the estimates in order to generate summary values. Of the 796 identified abstracts, 12 (1.5%) were included in this systematic review and meta-analysis. Poor gait performance predicted dementia [pooled hazard ratio (HR) combined with relative risk and odds ratio = 1.53 with P analysis provides evidence that poor gait performance predicts dementia. This association depends on the type of dementia; poor gait performance is a stronger predictor of non-AD dementias than AD. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Etiologies and risk factors for dementia

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Sandeep Grover

2016-01-01

Full Text Available Dementia is understood as a clinical syndrome characterized by impairment in memory impairment along with cognitive deficits in other domains. Over the years, understanding about the causes of dementias has improved. Broadly, dementias can be classified as irreversible degenerative dementias and reversible dementias. Alzheimer′s disease is the prototype of degenerative dementias and is characterized by the accumulation of beta-amyloid protein (called as amyloid plaques outside the neurons and accumulation of tau protein (called tau tangles inside the neurons. Vascular dementias are characterized by cerebrovascular insults which lead to pathological brain changes that impair cognition. The pathological hallmark of Lewy body dementia is the presence of α-synuclein neuronal inclusions, also known as Lewy bodies, accompanied by neuronal loss. Frontotemporal dementias are characterized by abnormal deposits of the microtubule-associated protein tau, the trans-activation response TAR DNA-binding protein with molecular weight 43 kDa (TDP-43, and the fused in sarcoma protein. Reversible dementias are characterized by the primary illness and may not present with characteristic brain deposits as seen with many degenerative dementias.

Molecular Pathways Bridging Frontotemporal Lobar Degeneration and Psychiatric Disorders

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Roberta eZanardini

2016-02-01

Full Text Available The overlap of symptoms between neurodegenerative and psychiatric diseases has been reported. Neuropsychiatric alterations are commonly observed in dementia, especially in the behavioral variant of frontotemporal dementia (bvFTD, which is the most common clinical FTD subtype. At the same time, psychiatric disorders, like schizophrenia, can display symptoms of dementia, including features of frontal dysfunction with relative sparing of memory. In the present review we discuss common molecular features in these pathologies with a special focus on FTD. Molecules like Brain Derived Neurotrophic Factor (BDNF and progranulin are linked to the pathophysiology of both neurodegenerative and psychiatric diseases. In these brain-associated illnesses, the presence of disease-associated variants in BDNF and progranulin (GRN genes cause a reduction of circulating proteins levels, through alterations in proteins expression or secretion. For these reasons, we believe that prevention and therapy of psychiatric and neurological disorders could be achieved enhancing both BDNF and progranulin levels thanks to drug discovery efforts.

Functional dissociation between anterior temporal lobe and inferior frontal gyrus in the processing of dynamic body expressions: Insights from behavioral variant frontotemporal dementia.

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Jastorff, Jan; De Winter, Francois-Laurent; Van den Stock, Jan; Vandenberghe, Rik; Giese, Martin A; Vandenbulcke, Mathieu

2016-12-01

Several brain regions are involved in the processing of emotional stimuli, however, the contribution of specific regions to emotion perception is still under debate. To investigate this issue, we combined behavioral testing, structural and resting state imaging in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and age matched controls, with task-based functional imaging in young, healthy volunteers. As expected, bvFTD patients were impaired in emotion detection as well as emotion categorization tasks, testing dynamic emotional body expressions as stimuli. Interestingly, their performance in the two tasks correlated with gray matter volume in two distinct brain regions, the left anterior temporal lobe for emotion detection and the left inferior frontal gyrus (IFG) for emotion categorization. Confirming this observation, multivoxel pattern analysis in healthy volunteers demonstrated that both ROIs contained information for emotion detection, but that emotion categorization was only possible from the pattern in the IFG. Furthermore, functional connectivity analysis showed reduced connectivity between the two regions in bvFTD patients. Our results illustrate that the mentalizing network and the action observation network perform distinct tasks during emotion processing. In bvFTD, communication between the networks is reduced, indicating one possible cause underlying the behavioral symptoms. Hum Brain Mapp 37:4472-4486, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Processing emotion from abstract art in frontotemporal lobar degeneration.

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Cohen, Miriam H; Carton, Amelia M; Hardy, Christopher J; Golden, Hannah L; Clark, Camilla N; Fletcher, Phillip D; Jaisin, Kankamol; Marshall, Charles R; Henley, Susie M D; Rohrer, Jonathan D; Crutch, Sebastian J; Warren, Jason D

2016-01-29

art may signal emotions independently of a biological or social carrier: it might therefore constitute a test case for defining brain mechanisms of generic emotion decoding and the impact of disease states on those mechanisms. This is potentially of particular relevance to diseases in the frontotemporal lobar degeneration (FTLD) spectrum. These diseases are often led by emotional impairment despite retained or enhanced artistic interest in at least some patients. However, the processing of emotion from art has not been studied systematically in FTLD. Here we addressed this issue using a novel emotional valence matching task on abstract paintings in patients representing major syndromes of FTLD (behavioural variant frontotemporal dementia, n=11; sematic variant primary progressive aphasia (svPPA), n=7; nonfluent variant primary progressive aphasia (nfvPPA), n=6) relative to healthy older individuals (n=39). Performance on art emotion valence matching was compared between groups taking account of perceptual matching performance and assessed in relation to facial emotion matching using customised control tasks. Neuroanatomical correlates of art emotion processing were assessed using voxel-based morphometry of patients' brain MR images. All patient groups had a deficit of art emotion processing relative to healthy controls; there were no significant interactions between syndromic group and emotion modality. Poorer art emotion valence matching performance was associated with reduced grey matter volume in right lateral occopitotemporal cortex in proximity to regions previously implicated in the processing of dynamic visual signals. Our findings suggest that abstract art may be a useful model system for investigating mechanisms of generic emotion decoding and aesthetic processing in neurodegenerative diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Interaction with the MAPT H1H1 Genotype Increases Dementia Risk in APOE ε4 Carriers in a Population of Southern India.

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Jairani, P S; Aswathy, P M; Gopala, Srinivas; Verghese, Joe; Mathuranath, P S

2016-01-01

This study delineates the role of the interaction of apolipoprotein E (APOE) and MAPT alleles in contributing to disease risks of dementia in a southern Indian population. A sample of 419 patients comprising Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87), frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control group (n = 138). APOE genotyping and MAPT haplotyping were performed on all study subjects. Multivariate logistic regression analysis showed that variability on the APOE locus influenced the relative risk of dementia in the study population. The APOE ε4 allele increased the disease risk most significantly for AD (OR = 3.468, p India when compared to other dementia groups, while the transcriptional differences between MAPT haplotypes have a limited role in Indian dementia patients. © 2016 S. Karger AG, Basel.

Behavioral and Neuroimaging Evidence for Facial Emotion Recognition in Elderly Korean Adults with Mild Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.

Science.gov (United States)

Park, Soowon; Kim, Taehoon; Shin, Seong A; Kim, Yu Kyeong; Sohn, Bo Kyung; Park, Hyeon-Ju; Youn, Jung-Hae; Lee, Jun-Young

2017-01-01

Background: Facial emotion recognition (FER) is impaired in individuals with frontotemporal dementia (FTD) and Alzheimer's disease (AD) when compared to healthy older adults. Since deficits in emotion recognition are closely related to caregiver burden or social interactions, researchers have fundamental interest in FER performance in patients with dementia. Purpose: The purpose of this study was to identify the performance profiles of six facial emotions (i.e., fear, anger, disgust, sadness, surprise, and happiness) and neutral faces measured among Korean healthy control (HCs), and those with mild cognitive impairment (MCI), AD, and FTD. Additionally, the neuroanatomical correlates of facial emotions were investigated. Methods: A total of 110 (33 HC, 32 MCI, 32 AD, 13 FTD) older adult participants were recruited from two different medical centers in metropolitan areas of South Korea. These individuals underwent an FER test that was used to assess the recognition of emotions or absence of emotion (neutral) in 35 facial stimuli. Repeated measures two-way analyses of variance were used to examine the distinct profiles of emotional recognition among the four groups. We also performed brain imaging and voxel-based morphometry (VBM) on the participants to examine the associations between FER scores and gray matter volume. Results: The mean score of negative emotion recognition (i.e., fear, anger, disgust, and sadness) clearly discriminated FTD participants from individuals with MCI and AD and HC [ F (3,106) = 10.829, p < 0.001, η 2 = 0.235], whereas the mean score of positive emotion recognition (i.e., surprise and happiness) did not. A VBM analysis showed negative emotions were correlated with gray matter volume of anterior temporal regions, whereas positive emotions were related to gray matter volume of fronto-parietal regions. Conclusion: Impairment of negative FER in patients with FTD is cross-cultural. The discrete neural correlates of FER indicate that emotional

Regional cerebral blood flow single photon emission computed tomography for detection of Frontotemporal dementia in people with suspected dementia.

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Archer, Hilary A; Smailagic, Nadja; John, Christeena; Holmes, Robin B; Takwoingi, Yemisi; Coulthard, Elizabeth J; Cullum, Sarah

2015-06-23

In the UK, dementia affects 5% of the population aged over 65 years and 25% of those over 85 years. Frontotemporal dementia (FTD) represents one subtype and is thought to account for up to 16% of all degenerative dementias. Although the core of the diagnostic process in dementia rests firmly on clinical and cognitive assessments, a wide range of investigations are available to aid diagnosis.Regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) is an established clinical tool that uses an intravenously injected radiolabelled tracer to map blood flow in the brain. In FTD the characteristic pattern seen is hypoperfusion of the frontal and anterior temporal lobes. This pattern of blood flow is different to patterns seen in other subtypes of dementia and so can be used to differentiate FTD.It has been proposed that a diagnosis of FTD, (particularly early stage), should be made not only on the basis of clinical criteria but using a combination of other diagnostic findings, including rCBF SPECT. However, more extensive testing comes at a financial cost, and with a potential risk to patient safety and comfort. To determine the diagnostic accuracy of rCBF SPECT for diagnosing FTD in populations with suspected dementia in secondary/tertiary healthcare settings and in the differential diagnosis of FTD from other dementia subtypes. Our search strategy used two concepts: (a) the index test and (b) the condition of interest. We searched citation databases, including MEDLINE (Ovid SP), EMBASE (Ovid SP), BIOSIS (Ovid SP), Web of Science Core Collection (ISI Web of Science), PsycINFO (Ovid SP), CINAHL (EBSCOhost) and LILACS (Bireme), using structured search strategies appropriate for each database. In addition we searched specialised sources of diagnostic test accuracy studies and reviews including: MEDION (Universities of Maastricht and Leuven), DARE (Database of Abstracts of Reviews of Effects) and HTA (Health Technology Assessment) database

Argentinian/Chilean validation of the Spanish-language version of Addenbrooke's Cognitive Examination III for diagnosing dementia.

Science.gov (United States)

Bruno, D; Slachevsky, A; Fiorentino, N; Rueda, D S; Bruno, G; Tagle, A R; Olavarria, L; Flores, P; Lillo, P; Roca, M; Torralva, T

2017-08-30

The Addenbrooke's Cognitive Examination III (ACE-III), an adaptation of the ACE cognitive screening test, has been demonstrated to have high sensitivity and specificity in detecting cognitive impairment in patients with dementia and other neurological and psychiatric disorders. Although the Spanish-language version of the ACE-III has already been validated in Spain, it is yet to be validated in Latin America. The aim of this study was to validate the ACE-III test in an Argentinean and Chilean population. ACE-III was administered to 70 patients with Alzheimer disease, 31 patients with behavioural variant frontotemporal dementia, and a control group of 139 healthy volunteers. Participants were recruited at centres in both countries. The Spanish-language version of ACE-III was found to have good internal consistency (Cronbach's alpha=0.87). We found significant differences in total ACE-III scores between patients with Alzheimer disease and controls (pcognitive dysfunction in patients with dementia. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Grey and white matter correlates of recent and remote autobiographical memory retrieval--insights from the dementias.

Directory of Open Access Journals (Sweden)

Muireann Irish

Full Text Available The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the

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...

PET studies in Alzheimer disease and other degenerative dementias

International Nuclear Information System (INIS)

Jeong, Yong; Na, Duk L.

2003-01-01

Neurodegenerative disorders cause a variety of dementia including Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and Huntington's disease. PET scan is useful for early detection and differential diagnosis of theses dementing disorders. Also, it provides valuable information about clinico-anatomical correlation, allowing better understanding of function of brain. Here we discuss recent achievements PET studies regarding these dementing disorders. Future progress in PET technology, new tracers, and image analysis will play an important role in further clarifying the disease pathophysiology and brain functions

Creativity with dementia patients. Can creativity and art stimulate dementia patients positively?

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Hannemann, Beat Ted

2006-01-01

Creative activities could be stimulating for dementia patients. This article gives a review of practical forms of treating dementia patients with art therapeutic indications. It is also a ground for long-term research objective: in brief, I take exception to such a view, contrary to the common belief in the society and some professionals in the healthcare of dementia patients, on the ground that the patients do not have the capacity to improve their own creativity. The theory of cognition tells us about the principle of being creative as a basis for human life. This specific principle is effective for the aged as well. In the long-term, the creative potential of old patients will be unblocked in individual and group therapy sessions. Creative activity has been shown to reduce depression and isolation, offering the power of choice and decisions. Towards the end of life, art and creativity offer a path of opening up the windows to people's emotional interiors. Creative- and art therapy provides possibilities that are mostly indicated to sharpen the capacity of the senses and the patients' propensity to act themselves. Nonverbal therapy methods, such as painting, music, etc., are able to influence the well-being of the patients positively, within the modern healthcare system in nursing homes. The elderly and some of the dementia patients take the initiative to combine creativity and arts and to define his/her feeling for aesthetical matters. Furthermore, group therapy sessions help against isolation and lack of life perspective and hope. Copyright 2006 S. Karger AG, Basel.

Face shape and face identity processing in behavioral variant fronto-temporal dementia: A specific deficit for familiarity and name recognition of famous faces.

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De Winter, François-Laurent; Timmers, Dorien; de Gelder, Beatrice; Van Orshoven, Marc; Vieren, Marleen; Bouckaert, Miriam; Cypers, Gert; Caekebeke, Jo; Van de Vliet, Laura; Goffin, Karolien; Van Laere, Koen; Sunaert, Stefan; Vandenberghe, Rik; Vandenbulcke, Mathieu; Van den Stock, Jan

2016-01-01

Deficits in face processing have been described in the behavioral variant of fronto-temporal dementia (bvFTD), primarily regarding the recognition of facial expressions. Less is known about face shape and face identity processing. Here we used a hierarchical strategy targeting face shape and face identity recognition in bvFTD and matched healthy controls. Participants performed 3 psychophysical experiments targeting face shape detection (Experiment 1), unfamiliar face identity matching (Experiment 2), familiarity categorization and famous face-name matching (Experiment 3). The results revealed group differences only in Experiment 3, with a deficit in the bvFTD group for both familiarity categorization and famous face-name matching. Voxel-based morphometry regression analyses in the bvFTD group revealed an association between grey matter volume of the left ventral anterior temporal lobe and familiarity recognition, while face-name matching correlated with grey matter volume of the bilateral ventral anterior temporal lobes. Subsequently, we quantified familiarity-specific and name-specific recognition deficits as the sum of the celebrities of which respectively only the name or only the familiarity was accurately recognized. Both indices were associated with grey matter volume of the bilateral anterior temporal cortices. These findings extent previous results by documenting the involvement of the left anterior temporal lobe (ATL) in familiarity detection and the right ATL in name recognition deficits in fronto-temporal lobar degeneration.

Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.

Science.gov (United States)

Broce, Iris; Karch, Celeste M; Wen, Natalie; Fan, Chun C; Wang, Yunpeng; Tan, Chin Hong; Kouri, Naomi; Ross, Owen A; Höglinger, Günter U; Muller, Ulrich; Hardy, John; Momeni, Parastoo; Hess, Christopher P; Dillon, William P; Miller, Zachary A; Bonham, Luke W; Rabinovici, Gil D; Rosen, Howard J; Schellenberg, Gerard D; Franke, Andre; Karlsen, Tom H; Veldink, Jan H; Ferrari, Raffaele; Yokoyama, Jennifer S; Miller, Bruce L; Andreassen, Ole A; Dale, Anders M; Desikan, Rahul S; Sugrue, Leo P

2018-01-01

Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal. We

Addenbrooke's Cognitive Examination (ACE) for the diagnosis and differential diagnosis of dementia.

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Larner, A J

2007-07-01

The Addenbrooke's Cognitive Examination (ACE) is reported to be a highly sensitive and specific "bedside" test for the diagnosis of dementia, but large pragmatic studies of its use in day-to-day clinical practice are lacking. This study measured diagnostic accuracy of ACE in a large cohort of consecutive patients referred to a dedicated Cognitive Function Clinic. Consecutive new referrals over a 3.5-year period were administered the ACE (n=285). ACE scores and subscores (VLOM ratio) were compared to clinical diagnoses of dementia and dementia subtype, established on the basis of widely accepted diagnostic criteria and at least 12-month follow-up. ACE had good sensitivity, specificity, and positive predictive value for the diagnosis of dementia, with excellent diagnostic accuracy as measured by area under the receiver operating characteristic curve. However, a lower cutoff than that used in the index paper was required for optimum test sensitivity and specificity. ACE VLOM ratio subscore for the differential diagnosis of Alzheimer's disease and frontotemporal dementia proved less accurate. This study suggests that ACE is useful for the diagnosis of dementia in routine clinical practice but that other instruments may be required for the differential diagnosis of the dementia syndrome.

Is the Frontal Assessment Battery reliable in ALS patients?

NARCIS (Netherlands)

Raaphorst, J.; Beeldman, E.; Jaeger, B.; Schmand, B.A.; Berg, L.H. van den; Weikamp, J.G.; Schelhaas, H.J.; Visser, M. de; Haan, R.J. de

2013-01-01

The assessment of frontal functions in ALS patients is important because of the overlap with the behavioural variant of frontotemporal dementia (bvFTD). We investigated the applicability and reliability of the Frontal Assessment Battery (FAB) within a cohort of predominantly prevalent ALS patients.

Stereotypic behaviors in degenerative dementias.

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Prioni, S; Fetoni, V; Barocco, F; Redaelli, V; Falcone, C; Soliveri, P; Tagliavini, F; Scaglioni, A; Caffarra, P; Concari, L; Gardini, S; Girotti, F

2012-11-01

Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in fronto-temporal dementia (FTD), but not studied in other types of degenerative dementias. The aim was to investigate stereotypy frequency and type in patients with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Parkinson's disease with dementia (PDD) in a multicenter observational study; and to investigate the relation of stereotypies to cognitive, behavioral and motor impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were examined by the five-domain Stereotypy Rating Inventory. Cognition was examined by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity by the Unified Parkinson's Disease Rating Scale part III, and activities of daily living. Stereotypies were present in all groups. FTD and PDD had the greatest frequency of one-domain stereotypies; FTD also had the greatest frequency of two-or-more domain stereotypies; movement stereotypies were the most common stereotypies in all groups. AD patients had fewer stereotypies than the other groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.

The Utility of the Addenbrooke's Cognitive Examination Version Three in Early-Onset Dementia.

Science.gov (United States)

Elamin, Marwa; Holloway, Guy; Bak, Thomas H; Pal, Suvankar

2016-01-01

Early-onset dementia (EOD) is defined as functionally relevant cognitive decline with age of onset at less than 65 years. The aim of this study was to investigate the utility of the recently validated third version of the Addenbrooke's Cognitive Examination (ACE-III) in predicting dementia diagnoses in EOD. ACE-III scores of EOD patients were compared to those of healthy controls (HC) and individuals with subjective memory impairment (SMI). The study included 71 EOD patients (Alzheimer's disease, n = 31; primary progressive aphasia, n = 11; behavioural-variant frontotemporal dementia, n = 18, and posterior cortical atrophy, n = 11); there were 28 HC and 15 individuals with SMI. At a cut-off score of 88/100, the ACE-III displayed high sensitivity and specificity in distinguishing EOD from HC (91.5 and 96.4%) and SMI (91.5 and 86.7%). The ACE-III is a reliable cognitive screening tool in EOD. © 2015 S. Karger AG, Basel.

Behavioral and Neuroimaging Evidence for Facial Emotion Recognition in Elderly Korean Adults with Mild Cognitive Impairment, Alzheimer’s Disease, and Frontotemporal Dementia

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Soowon Park

2017-11-01

Full Text Available Background: Facial emotion recognition (FER is impaired in individuals with frontotemporal dementia (FTD and Alzheimer’s disease (AD when compared to healthy older adults. Since deficits in emotion recognition are closely related to caregiver burden or social interactions, researchers have fundamental interest in FER performance in patients with dementia.Purpose: The purpose of this study was to identify the performance profiles of six facial emotions (i.e., fear, anger, disgust, sadness, surprise, and happiness and neutral faces measured among Korean healthy control (HCs, and those with mild cognitive impairment (MCI, AD, and FTD. Additionally, the neuroanatomical correlates of facial emotions were investigated.Methods: A total of 110 (33 HC, 32 MCI, 32 AD, 13 FTD older adult participants were recruited from two different medical centers in metropolitan areas of South Korea. These individuals underwent an FER test that was used to assess the recognition of emotions or absence of emotion (neutral in 35 facial stimuli. Repeated measures two-way analyses of variance were used to examine the distinct profiles of emotional recognition among the four groups. We also performed brain imaging and voxel-based morphometry (VBM on the participants to examine the associations between FER scores and gray matter volume.Results: The mean score of negative emotion recognition (i.e., fear, anger, disgust, and sadness clearly discriminated FTD participants from individuals with MCI and AD and HC [F(3,106 = 10.829, p < 0.001, η2 = 0.235], whereas the mean score of positive emotion recognition (i.e., surprise and happiness did not. A VBM analysis showed negative emotions were correlated with gray matter volume of anterior temporal regions, whereas positive emotions were related to gray matter volume of fronto-parietal regions.Conclusion: Impairment of negative FER in patients with FTD is cross-cultural. The discrete neural correlates of FER indicate that

Behavioral and Neuroimaging Evidence for Facial Emotion Recognition in Elderly Korean Adults with Mild Cognitive Impairment, Alzheimer’s Disease, and Frontotemporal Dementia

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Park, Soowon; Kim, Taehoon; Shin, Seong A; Kim, Yu Kyeong; Sohn, Bo Kyung; Park, Hyeon-Ju; Youn, Jung-Hae; Lee, Jun-Young

2017-01-01

Background: Facial emotion recognition (FER) is impaired in individuals with frontotemporal dementia (FTD) and Alzheimer’s disease (AD) when compared to healthy older adults. Since deficits in emotion recognition are closely related to caregiver burden or social interactions, researchers have fundamental interest in FER performance in patients with dementia. Purpose: The purpose of this study was to identify the performance profiles of six facial emotions (i.e., fear, anger, disgust, sadness, surprise, and happiness) and neutral faces measured among Korean healthy control (HCs), and those with mild cognitive impairment (MCI), AD, and FTD. Additionally, the neuroanatomical correlates of facial emotions were investigated. Methods: A total of 110 (33 HC, 32 MCI, 32 AD, 13 FTD) older adult participants were recruited from two different medical centers in metropolitan areas of South Korea. These individuals underwent an FER test that was used to assess the recognition of emotions or absence of emotion (neutral) in 35 facial stimuli. Repeated measures two-way analyses of variance were used to examine the distinct profiles of emotional recognition among the four groups. We also performed brain imaging and voxel-based morphometry (VBM) on the participants to examine the associations between FER scores and gray matter volume. Results: The mean score of negative emotion recognition (i.e., fear, anger, disgust, and sadness) clearly discriminated FTD participants from individuals with MCI and AD and HC [F(3,106) = 10.829, p emotion recognition (i.e., surprise and happiness) did not. A VBM analysis showed negative emotions were correlated with gray matter volume of anterior temporal regions, whereas positive emotions were related to gray matter volume of fronto-parietal regions. Conclusion: Impairment of negative FER in patients with FTD is cross-cultural. The discrete neural correlates of FER indicate that emotional recognition processing is a multi-modal system in the brain

Moral processing deficit in behavioral variant frontotemporal dementia is associated with facial emotion recognition and brain changes in default mode and salience network areas.

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Van den Stock, Jan; Stam, Daphne; De Winter, François-Laurent; Mantini, Dante; Szmrecsanyi, Benedikt; Van Laere, Koen; Vandenberghe, Rik; Vandenbulcke, Mathieu

2017-12-01

Behavioral variant frontotemporal dementia (bvFTD) is associated with abnormal emotion recognition and moral processing. We assessed emotion detection, discrimination, matching, selection, and categorization as well as judgments of nonmoral, moral impersonal, moral personal low- and high-conflict scenarios. bvFTD patients gave more utilitarian responses on low-conflict personal moral dilemmas. There was a significant correlation between a facial emotion processing measure derived through principal component analysis and utilitarian responses on low-conflict personal scenarios in the bvFTD group (controlling for MMSE-score and syntactic abilities). Voxel-based morphometric multiple regression analysis in the bvFTD group revealed a significant association between the proportion of utilitarian responses on personal low-conflict dilemmas and gray matter volume in ventromedial prefrontal areas ( p height  emotions in moral cognition and suggest a common basis for deficits in both abilities, possibly related to reduced experience of emotional sensations. At the neural level abnormal moral cognition in bvFTD is related to structural integrity of the medial prefrontal cortex and functional characteristics of the anterior insula. The present findings provide a common basis for emotion recognition and moral reasoning and link them with areas in the default mode and salience network.

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

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Laura E. Downey

2015-01-01

Full Text Available 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 progressive aphasia (svPPA; n = 15, relative to healthy older individuals (n = 37 using two components of the Awareness of Social Inference Test, canonical emotion identification and sarcasm identification. Diffusion tensor imaging (DTI was used to derive white matter tract correlates of social cognition performance and compared with the distribution of grey matter atrophy on voxel-based morphometry. The bvFTD and svPPA groups showed comparably severe deficits for identification of canonical emotions and sarcasm, and these deficits were correlated with distributed and overlapping white matter tract alterations particularly affecting frontotemporal connections in the right cerebral hemisphere. The most robust DTI associations were identified in white matter tracts linking cognitive and evaluative processing with emotional responses: anterior thalamic radiation, fornix (emotion identification and uncinate fasciculus (sarcasm identification. DTI associations of impaired social cognition were more consistent than corresponding grey matter associations. These findings delineate a brain network substrate for the social impairment that characterises FTLD syndromes. The findings further suggest that DTI can generate sensitive and functionally relevant indexes of white matter damage in FTLD, with potential to transcend conventional syndrome boundaries.

Occult CSF flow disturbance of patients with Alzheimer type dementia and vascular dementia

International Nuclear Information System (INIS)

Kono, Kazuhiko; Sugita, Yasuko; Funaki, Chiaki

1994-01-01

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)

A Modified Reading the Mind in the Eyes Test Predicts Behavioral Variant Frontotemporal Dementia Better Than Executive Function Tests

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Matthias L. Schroeter

2018-01-01

Full Text Available Behavioral variant frontotemporal dementia (bvFTD is characterized by deep alterations in behavior and personality. Although revised diagnostic criteria agree for executive dysfunction as most characteristic, impairments in social cognition are also suggested. The study aimed at identifying those neuropsychological and behavioral parameters best discriminating between bvFTD and healthy controls. Eighty six patients were diagnosed with possible or probable bvFTD according to Rascovsky et al. (2011 and compared with 43 healthy age-matched controls. Neuropsychological performance was assessed with a modified Reading the Mind in the Eyes Test (RMET, Stroop task, Trail Making Test (TMT, Hamasch-Five-Point Test (H5PT, and semantic and phonemic verbal fluency tasks. Behavior was assessed with the Apathy Evaluation Scale, Frontal Systems Behavioral Scale, and Bayer Activities of Daily Living Scale. Each test’s discriminatory power was investigated by Receiver Operating Characteristic curves calculating the area under the curve (AUC. bvFTD patients performed significantly worse than healthy controls in all neuropsychological tests. Discriminatory power (AUC was highest in behavioral questionnaires, high in verbal fluency tasks and the RMET, and lower in executive function tests such as the Stroop task, TMT and H5PT. As fluency tasks depend on several cognitive functions, not only executive functions, results suggest that the RMET discriminated better between bvFTD and control subjects than other executive tests. Social cognition should be incorporated into diagnostic criteria for bvFTD in the future, such as in the International Classification of Diseases (ICD-11, as already suggested in the Diagnostic and Statistical Manual for Mental Disorders (DSM-5.

[Neuroepigenetics: Desoxyribonucleic acid methylation in Alzheimer's disease and other dementias].

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Mendioroz Iriarte, Maite; Pulido Fontes, Laura; Méndez-López, Iván

2015-05-21

DNA methylation is an epigenetic mechanism that controls gene expression. In Alzheimer's disease (AD), global DNA hypomethylation of neurons has been described in the human cerebral cortex. Moreover, several variants in the methylation pattern of candidate genes have been identified in brain tissue when comparing AD patients and controls. Specifically, DNA methylation changes have been observed in PSEN1 and APOE, both genes previously being involved in the pathophysiology of AD. In other degenerative dementias, methylation variants have also been described in key genes, such as hypomethylation of the SNCA gene in Parkinson's disease and dementia with Lewy bodies or hypermethylation of the GRN gene promoter in frontotemporal dementia. The finding of aberrant DNA methylation patterns shared by brain tissue and peripheral blood opens the door to use those variants as epigenetic biomarkers in the diagnosis of neurodegenerative diseases. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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...... to evaluate factors independently associated with the prescription of other psychotropic drug classes among patients already using antipsychotics. RESULTS: Among all patients registered with dementia (34,553), 25.3% (8,728) used ≥2 psychotropic drugs. Among patients treated with antipsychotics 75.8% (5...... of psychotropic drugs was antipsychotics and antidepressants. CONCLUSION: Concomitant use of psychotropic drugs was frequent in dementia patients. Patients living in nursing homes had the highest risk of receiving a combination of antipsychotics and other psychotropic drugs. Concomitant use of psychotropics may...

New possibility of traditional Chinese and Japanese medicine as treatment for behavioral and psychiatric symptoms in dementia

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Kung FC

2012-10-01

Full Text Available Fan-Chin Kung,1 Ryouhei Ishii,2 Hsing-Cheng Liu,3 Masatoshi Takeda21Yuli Hospital, DOH, Hualien, Taiwan; 2Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan; 3Department of General Psychiatry, Taipei City Psychiatric Center, Taipei, TaiwanAbstract: Yokukansan, one of the Kampo prescriptions, is composed of seven herbaceous plants and was developed in China in the 16th century as a cure for restlessness and agitation in children. Yokukansan has also become a popular drug combination in Japan, especially for the behavioral and psychiatric symptoms of dementia (BPSD. Recent studies have shown that yokukansan might also be quite effective against BPSD occurring in association with other types of dementia, such as Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, frontotemporal dementia, and vascular dementia. Researchers have intensively investigated yokukansan, focusing on the pharmacological mechanisms against glutamate-mediated excitotoxicity. This traditional Chinese and Japanese medicine holds potential promise for improving BPSD in elderly patients suffering from dementia.Keywords: yokukansan, dementia, Alzheimer's disease, behavioral and psychological symptoms of dementia, Kampo, glutamate

Trajectories of Behavioural Disturbances Across Dementia Types.

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Linds, Alexandra B; Kirstein, Alana B; Freedman, Morris; Verhoeff, Nicolaas P L G; Wolf, Uri; Chow, Tiffany W

2015-11-01

To replicate a previous finding that the trajectory of the Neuropsychiatric Inventory (NPI) shifts in the sixth year of behavioural variant frontotemporal dementia (bvFTD). We evaluated longitudinal tracking with both the Frontal Behavioural Inventory (FBI) and NPI, comparing bvFTD against other dementias. Chart reviews over two to five years for patients with bvFTD (n=30), primary progressive aphasia (PPA, n=13) and Alzheimer's disease (AD, n=118) at an urban Canadian tertiary clinic specializing in dementia. Linear regressions of the longitudinal data tested predictors of annualized rates of change (ROC) in NPI and FBI total and subscales for apathy and disinhibition among dementia groups. The mode of the overall sample for the most advanced duration of illness observed was 5 years, with the median at 7 years. We did not find a crescendo-decrescendo pattern in scores although, for bvFTD and AD, high initial scores correlated with ensuing downward ROCs on the NPI and FBI. Educational level showed an influence on disinhibition ROCs. The FBI was no more revealing than the NPI for apathy and disinhibition scores in these dementias. A cognitive reserve effect on behavioural disturbance was supported but it may take longer than our 4 years of observing the clinical sample to record inflection points in the behavioural and psychiatric symptoms seen in bvFTD. The current data only imply that both apathy and disinhibition will diminish over the course of dementia.

ANXA11 mutations prevail in Chinese ALS patients with and without cognitive dementia.

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Zhang, Kang; Liu, Qing; Liu, Keqiang; Shen, Dongchao; Tai, Hongfei; Shu, Shi; Ding, Qingyun; Fu, Hanhui; Liu, Shuangwu; Wang, Zhili; Li, Xiaoguang; Liu, Mingsheng; Zhang, Xue; Cui, Liying

2018-06-01

To investigate the genetic contribution of ANXA11 , a gene associated with amyotrophic lateral sclerosis (ALS), in Chinese ALS patients with and without cognitive dementia. Sequencing all the coding exons of ANXA11 and intron-exon boundaries in 18 familial amyotrophic lateral sclerosis (FALS), 353 unrelated sporadic amyotrophic lateral sclerosis (SALS), and 12 Chinese patients with ALS-frontotemporal lobar dementia (ALS-FTD). The transcripts in peripheral blood generated from a splicing mutation were examined by reverse transcriptase PCR. We identified 6 nonsynonymous heterozygous mutations (5 novel and 1 recurrent), 1 splice site mutation, and 1 deletion of 10 amino acids (not accounted in the mutant frequency) in 11 unrelated patients, accounting for a mutant frequency of 5.6% (1/18) in FALS, 2.3% (8/353) in SALS, and 8.3% (1/12) in ALS-FTD. The deletion of 10 amino acids was detected in 1 clinically undetermined male with an ALS family history who had atrophy in hand muscles and myotonic discharges revealed by EMG. The novel p. P36R mutation was identified in 1 FALS index, 1 patient with SALS, and 1 ALS-FTD. The splicing mutation (c.174-2A>G) caused in-frame skipping of the entire exon 6. The rest missense mutations including p.D40G, p.V128M, p.S229R, p.R302C and p.G491R were found in 6 unrelated patients with SALS. The ANXA11 gene is one of the most frequently mutated genes in Chinese patients with SALS. A canonical splice site mutation leading to skipping of the entire exon 6 further supports the loss-of-function mechanism. In addition, the study findings further expand the ANXA11 phenotype, first highlighting its pathogenic role in ALS-FTD.

Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease

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Laura Ibanez

2018-04-01

Full Text Available Background: The prevalence of dementia in Parkinson disease (PD increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established.Objective: To assess the contribution of coding variants in Mendelian dementia-causing genes on the risk of developing PD and the effect on cognitive performance of PD patients.Methods: We analyzed the coding regions of the amyloid-beta precursor protein (APP, Presenilin 1 and 2 (PSEN1, PSEN2, and Granulin (GRN genes from 1,374 PD cases and 973 controls using pooled-DNA targeted sequence, human exome-chip and whole-exome sequencing (WES data by single variant and gene base (SKAT-O and burden tests analyses. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE or the Montreal Cognitive Assessment (MoCA. The effect of coding variants in dementia-causing genes on cognitive performance was tested by multiple regression analysis adjusting for gender, disease duration, age at dementia assessment, study site and APOE carrier status.Results: Known AD pathogenic mutations in the PSEN1 (p.A79V and PSEN2 (p.V148I genes were found in 0.3% of all PD patients. There was a significant burden of rare, likely damaging variants in the GRN and PSEN1 genes in PD patients when compared with frequencies in the European population from the ExAC database. Multiple regression analysis revealed that PD patients carrying rare variants in the APP, PSEN1, PSEN2, and GRN genes exhibit lower cognitive tests scores than non-carrier PD patients (p = 2.0 × 10−4, independent of age at PD diagnosis, age at evaluation, APOE status or recruitment site.Conclusions: Pathogenic mutations in

Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein.

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Grangeon, Lou; Paquet, Claire; Bombois, Stephanie; Quillard-Muraine, Muriel; Martinaud, Olivier; Bourre, Bertrand; Lefaucheur, Romain; Nicolas, Gaël; Dumurgier, Julien; Gerardin, Emmanuel; Jan, Mary; Laplanche, Jean-Louis; Peoc'h, Katell; Hugon, Jacques; Pasquier, Florence; Maltête, David; Hannequin, Didier; Wallon, David

2016-01-01

Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer's disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses. Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD. Patients (n = 202) with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria. Patients were diagnosed with AD (n = 148, 73.2%), mixed dementia (n = 38, 18.8%), CJD, vascular dementia (n = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p < 0.0001). Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD.

Uncovering the Neural Bases of Cognitive and Affective Empathy Deficits in Alzheimer's Disease and the Behavioral-Variant of Frontotemporal Dementia.

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Dermody, Nadene; Wong, Stephanie; Ahmed, Rebekah; Piguet, Olivier; Hodges, John R; Irish, Muireann

2016-05-30

Loss of empathy is a core presenting feature of the behavioral-variant of frontotemporal dementia (bvFTD), resulting in socioemotional difficulties and behavioral transgressions. In contrast, interpersonal functioning remains relatively intact in Alzheimer's disease (AD), despite marked cognitive decline. The neural substrates mediating these patterns of loss and sparing in social functioning remain unclear, yet are relevant for our understanding of the social brain. We investigated cognitive versus affective aspects of empathy using the Interpersonal Reactivity Index (IRI) in 25 AD and 24 bvFTD patients and contrasted their performance with 22 age- and education-matched controls. Cognitive empathy was comparably compromised in AD and bvFTD, whereas affective empathy was impaired exclusively in bvFTD. While controlling for overall cognitive dysfunction ameliorated perspective-taking deficits in AD, empathy loss persisted across cognitive and affective domains in bvFTD. Voxel-based morphometry analyses revealed divergent neural substrates of empathy loss in each patient group. Perspective-taking deficits correlated with predominantly left-sided temporoparietal atrophy in AD, whereas widespread bilateral frontoinsular, temporal, parietal, and occipital atrophy was implicated in bvFTD. Reduced empathic concern in bvFTD was associated with atrophy in the left orbitofrontal, inferior frontal, and insular cortices, and the bilateral mid-cingulate gyrus. Our findings suggest that social cognitive deficits in AD arise largely as a consequence of global cognitive dysfunction, rather than a loss of empathy per se. In contrast, loss of empathy in bvFTD reflects the deterioration of a distributed network of frontoinsular and temporal structures that appear crucial for monitoring and processing social information.

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

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...... gene mutation carriers. CONCLUSIONS: This finding suggests that mutations in CHMP2B have widespread effects throughout the brain, leading to a neuro-anatomical signature distinct from other diseases in the frontotemporal lobar degeneration spectrum........ 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...

[Visual art, creativity and dementia].

Science.gov (United States)

Serrano, C; Allegri, R F; Martelli, M; Taragano, F; Rinalli, P

2005-01-01

Visual art is an expression of neurological function and how it organizes and interprets perception. The art is predominantly in the right hemisphere, in contrast, the left side, have inhibitory effects on artistic expression. In normal subjects, inhibitory and excitatory mechanisms could interact in a complex harmony, reflecting a paradoxical functional facilitation. Brain diseases such as dementia could change this harmony and then, alter the artistic abilities. Evaluate the art expression in the degenerative diseases. Artistic abilities of 3 painters with degenerative diseases were assessment. Patient 1: A 83 - year old right handed female, diagnosis: Alzheimer's disease. Artistic description: low productivity, simplified versions of earlier and alteration of the visuospatial organization. Patient 2: A 78-year-old right handed female, diagnosis: Primary Progressive Aphasia (PPA); Artistic description: oversimplified drawings which maintaining overall spatial organization, without impair artistic skills. Patient 3: A 68 year-old right handed woman, diagnosis: Fronto-Temporal Dementia (FTD). Artistic description: Increased artistic activity, originality, freedom, utilization of intense colours with perseverative and repetitive copying of similar paintings of her own work. Visual art in Alzheimer's disease is a consequence of visuospatial and constructive disabilities. In contrast, the conservation of this cognitive functions and left asymmetrical involved, in FTD and PPA respectively, suggest artistic preservation, independently of the language injury. The disproportionate functional prevalence of the right over the left could lead to a release of novelty - seeking in art and can contribute to emergent creativity. These observations suggest an organization for art in the brain and proposed bases for further investigations in dementias.

Hexanucleotide Repeat Expansion in C9ORF72 Is Not Detected in the Treatment-Resistant Schizophrenia Patients of Chinese Han.

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Xijia Xu

Full Text Available Hexanucleotide (GGGGCC repeat expansion in C9ORF72 (HRE causes frontotemporal lobar degeneration, frontotemporal dementia-amyotrophic lateral sclerosis, and amyotrophic lateral sclerosis. HRE was also seen in the genomes of patients suffering from several other degenerative diseases. However, whether it is present in the treatment-resistant schizophrenia patients remains unknown. Genotyping 386 patients suffering from treatment-resistant schizophrenia using the method of Repeat-Primed PCR, we reported here that no HRE was detected in the patients of Chinese Han.

Souvenaid reduces behavioral deficits and improves social cognition skills in frontotemporal dementia: a proof-of-concept study.

Science.gov (United States)

Pardini, Matteo; Serrati, Carlo; Guida, Silvia; Mattei, Chiara; Abate, Lucia; Massucco, Davide; Sassos, Davide; Amore, Mario; Krueger, Frank; Cocito, Leonardo; Emberti Gialloreti, Leonardo

2015-01-01

Souvenaid™ is a nutraceutical compound thought to positively enhance synaptic function. In line with this mechanism of action, Souvenaid™ has been shown to improve cognitive function in subjects with mild Alzheimer's disease in randomized clinical trials. To date, however, the potential of Souvenaid™ to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored. To evaluate the impact of Souvenaid™ on executive functions, social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia (bv-FTD). Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid™ (125 ml/day) or placebo groups. After 12 weeks, subjects were switched between the two groups. All subjects, blinded to treatment, underwent clinical and cognitive evaluations at enrollment, after 12 weeks and after 24 weeks. Treatment with Souvenaid™ was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo, which both returned to baseline when Souvenaid™ was discontinued. Souvenaid™ did not have an effect on executive functions. Our results provide evidence of the potential of Souvenaid™ therapy for the treatment of behavioral disturbances and social cognition skills in FTD. © 2015 S. Karger AG, Basel.

Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability

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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.

Screening UBQLN-2 in French frontotemporal lobar degeneration and frontotemporal lobar degeneration-amyotrophic lateral sclerosis patients.

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Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Pariente, Jérémie; Brice, Alexis; Kabashi, Edor

2013-08-01

The ubiquilin-2 gene (UBQLN-2) is the only amyotrophic lateral sclerosis (ALS)-related gene mapping on the X chromosome. Mutations in the PXX domain of UBQLN-2 have been first described in ALS patients with a mutational frequency of 2.6% in familial ALS cases with no evidence of male-to-male transmission. Different populations have been further tested with mutations largely distributed in the gene and lower frequency of positive cases. To determine the genetic contribution of UBQLN-2 in frontotemporal lobar degeneration (FTLD) and FTLD-ALS, we screened a cohort of 136 French patients, identifying a missense variant (c.1006A>G; p.T336A) in 1 FTLD patient whose biological relevance to disease is questionable. We conclude that UBQLN-2 mutations related to ALS/FTLD are extremely rare in French FTLD and FTLD-ALS patients and should not be analyzed systematically. Copyright © 2013. Published by Elsevier Inc.

Dementia as a predictor of mortality in adult trauma patients.

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Jordan, Benjamin C; Brungardt, Joseph; Reyes, Jared; Helmer, Stephen D; Haan, James M

2018-01-01

The specific contribution of dementia towards mortality in trauma patients is not well defined. The purpose of the study was to evaluate dementia as a predictor of mortality in trauma patients when compared to case-matched controls. A 5-year retrospective review was conducted of adult trauma patients with a diagnosis of dementia at an American College of Surgeons-verified level I trauma center. Patients with dementia were matched with non-dementia patients and compared on mortality, ICU length of stay, and hospital length of stay. A total of 195 patients with dementia were matched to non-dementia controls. Comorbidities and complications (11.8% vs 12.4%) were comparable between both groups. Dementia patients spent fewer days on the ventilator (1 vs 4.5, P = 0.031). The length of ICU stay (2 days), hospital length of stay (3 days), and mortality (5.1%) were the same for both groups (P > 0.05). Dementia does not appear to increase the risk of mortality in trauma patients. Further studies should examine post-discharge outcomes in dementia patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of F-18 FDG-PET for the Clinical Multidisciplinary Evaluation of Dementia

DEFF Research Database (Denmark)

Prakash, Vineet; Vestergård, Karsten; Frost, Majbritt

PURPOSE            Dementia is a challenging clinical diagnosis. Compared with conventional clinical evaluations, F-18 Fluorodeoxyglucose (FDG) PET has been reported to improve not only the diagnostic accuracy of dementia but also help better define the underlying  type. This is because FDG PET d...... or Frontotemporal dementia.                       CLINICAL RELEVANCE/APPLICATION            F18-FDG Brain PET with visual and automated analyses can be valuable  in a diagnostic algorithim for the work up of dementia when the cause is uncertain.......PURPOSE            Dementia is a challenging clinical diagnosis. Compared with conventional clinical evaluations, F-18 Fluorodeoxyglucose (FDG) PET has been reported to improve not only the diagnostic accuracy of dementia but also help better define the underlying  type. This is because FDG PET...... patients had FDG-PET scans with visual and automated analyses. At a multidisciplinary meeting attended by a neuroradiologist and PET specialist, a pre-PET diagnosis, type of dementia and management plan was composed by a neurologist on the basis of clinical assessment, MRI, neuropsychometry...

Right anterior temporal lobe dysfunction underlies theory of mind impairments in semantic dementia.

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

2014-04-01

Semantic dementia is a progressive neurodegenerative disorder characterized by the amodal and profound loss of semantic knowledge attributable to the degeneration of the left anterior temporal lobe. Although traditionally conceptualized as a language disorder, patients with semantic dementia display significant alterations in behaviour and socioemotional functioning. Recent evidence points to an impaired capacity for theory of mind in predominantly left-lateralized cases of semantic dementia; however, it remains unclear to what extent semantic impairments contribute to these deficits. Further the neuroanatomical signature of such disturbance remains unknown. Here, we sought to determine the neural correlates of theory of mind performance in patients with left predominant semantic dementia (n=11), in contrast with disease-matched cases with behavioural-variant frontotemporal dementia (n=10) and Alzheimer's disease (n=10), and healthy older individuals (n=14) as control participants. Participants completed a simple cartoons task, in which they were required to describe physical and theory of mind scenarios. Irrespective of subscale, patients with semantic dementia exhibited marked impairments relative to control subjects; however, only theory of mind deficits persisted when we covaried for semantic comprehension. Voxel-based morphometry analyses revealed that atrophy in right anterior temporal lobe structures, including the right temporal fusiform cortex, right inferior temporal gyrus, bilateral temporal poles and amygdalae, correlated significantly with theory of mind impairments in the semantic dementia group. Our results point to the marked disruption of cognitive functions beyond the language domain in semantic dementia, not exclusively attributable to semantic processing impairments. The significant involvement of right anterior temporal structures suggests that with disease evolution, the encroachment of pathology into the contralateral hemisphere heralds the

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

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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.

Progression to dementia in memory clinic patients without dementia: a latent profile analysis

NARCIS (Netherlands)

Kohler, S.; Hamel, R.; Sistermans, N.; Koene, T.; Pijnenburg, Y.A.L.; van der Flier, W.M.; Scheltens, P.; Visser, P.J.; Aalten, P.; Verhey, F. R. J.; Ramakers, I.

2013-01-01

Objective: To identify the existence of discrete cognitive subtypes among memory clinic patients without dementia and test their prognostic values. Methods: In a retrospective cohort study of 635 patients without dementia visiting the Alzheimer centers in Maastricht or Amsterdam, latent profile

Cognitive decline in patients with Alzheimer's disease, vascular dementia and senile dementia of Lewy body type.

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Ballard, C; Patel, A; Oyebode, F; Wilcock, G

1996-05-01

One hundred and twenty-four patients with DSM-III-R dementia were assessed with a standardized battery which included the Geriatric Mental State Schedule, the History and Aetiology Schedule, the Secondary Dementia Schedule and the CAMCOG. Patients with Alzheimer's disease, vascular dementia and senile dementia of Lewy body type (SDLT) all had a similar degree of cognitive impairment at the time of the baseline interview. Patients with Alzheimer's disease and vascular dementia each experienced a mean decline of 27 points in patients with SDLT. Patients with SDLT had a significantly greater decline of verbal fluency than both the other groups. Women were significantly more impaired than men at the time of the baseline assessment but experienced a similar decline during the year of follow-up.

Clinical Spectrum, Risk Factors, and Behavioral Abnormalities among Dementia Subtypes in a North Indian Population: A Hospital-Based Study

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Suman Kushwaha

2017-07-01

Full Text Available Background: As variability in the clinical profile of dementia subtypes had been reported with regional differences across the world, we conducted a retrospective hospital-based study in a North Indian population. Methods: We retrieved patient records from 2007 to 2014 for details of clinical evaluation, diagnosis, neuroimaging, biochemical investigations, and follow-up of 1,876 patients with dementia (PwD, and the data were analyzed using descriptive statistics. Results: Of the total PwD, Alzheimer disease (AD accounted for 30% followed by vascular dementia (VaD 26%, mixed dementia (MD 21%, Parkinson-related dementia 11%, frontotemporal dementia (FTD 7%, and infective dementia 5%. Of all PwD excluding the infective group (n = 1,777, 63% were men, 39% were from rural areas, 87% had behavioral abnormalities along with cognitive deficits, and 73% had impaired ADLs. Among dementia subtypes, a positive family history, cardiovascular and metabolic risk factors, and behavioral abnormalities were found to be distributed. However, there existed a predominance of specific behavioral pattern in each subtype. The mean duration of follow-up varied from 2.9 ± 2.3 (VaD to 3.6 ± 2.1 (AD and greater than 30% were found to be stable on treatment (except in dementia with Lewy body. Conclusions: This large hospital-based study provides a distribution pattern and clinical spectrum of dementia subtypes in a North Indian population.

Frontotemporal lobar degeneration with ubiquitin pathology: an autopsy case presenting with semantic dementia and upper motor neuron signs with a clinical course of 19 years.

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Yokota, Osamu; Tsuchiya, Kuniaki; Itoh, Yoshinori; Ishizu, Hideki; Akiyama, Haruhiko; Ikeda, Manabu; Kuzuhara, Shigeki; Otomo, Eiichi

2006-12-01

We report a case of a right-handed 74-year-old man who showed semantic dementia with a disease duration of 19 years. He initially presented with excessive use of pronouns and semantic paraphasia at the age of 55 years. Impairment of object recognition developed 5 years after the onset. Face recognition impairment and stereotypic behaviors developed 11 years after onset, and pyramidal signs 2 years before death. Pathological examination disclosed circumscribed severe atrophy in not only the bilateral temporal tips but also in the left precentral gyrus and pars opercularis in a motor speech field. Pyramidal tract involvement and loss of Betz cells were also evident. On the other hand, neurons in the anterior horns and hypoglossal nuclei were spared in number, although astrocytes were mildly proliferated. Ubiquitin-positive lesions were observed in the hippocampus, and frontal and temporal cortices. Neither Bunina bodies nor Pick bodies were present. These features clinically fit the international diagnostic criteria of semantic dementia and, histopathologically, frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). This case suggests that (1) the distribution of cortical lesions associated with language disturbance is not uniform in FTLD-MND. It may be that only some cases of FTLD with ubiquitin pathology develop semantic dementia despite the high incidence of language disturbance, and (2) the precentral gyrus can be severely affected in FTLD-MND. After reviewing previous cases of FTLD-MND with a clinical course of more than 10 years, we also noticed that (3) FTLD-MND cases with a long disease duration often show upper motor neuron-predominant involvement.

Usefulness of the pterion plate in frontotemporal craniotomy

International Nuclear Information System (INIS)

Goto, Akiko; Aoki, Yoshinori; Kano, Toshiyuki

2008-01-01

The objective of this study was to evaluate the usefulness of the pterion plate in preventing depression of the lateral side of the orbita after frontotemporal craniotomy. Forty patients who underwent frontotemporal craniotomy at our facility were studied: 20 received pterion plates during surgery (pterion plate group) and 20 did not (non-pterion plate group). In all patients, postoperative bone window CT was used to confirm the presence or absence of a depression (≥5 mm) on the lateral side of the orbita. Patient satisfaction was assessed by a questionnaire. Depression of the lateral side of the orbita on postoperative bone window CT was noted in none of the subjects in the pterion plate group and in 12 (60%) of the subjects in the non-pterion plate group (p<0.01). Patient satisfaction was higher in the pterion plate than in the non-pterion plate group (p<0.01). Findings from bone window CT and the questionnaire indicate that the pterion plate is effective in preventing postoperative depression of the lateral side of the orbita during frontotemporal craniotomy. (author)

Bilingualism, dementia, cognitive and neural reserve.

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Perani, Daniela; Abutalebi, Jubin

2015-12-01

We discuss the role of bilingualism as a source of cognitive reserve and we propose the putative neural mechanisms through which lifelong bilingualism leads to a neural reserve that delays the onset of dementia. Recent findings highlight that the use of more than one language affects the human brain in terms of anatomo-structural changes. It is noteworthy that recent evidence from different places and cultures throughout the world points to a significant delay of dementia onset in bilingual/multilingual individuals. This delay has been reported not only for Alzheimer's dementia and its prodromal mild cognitive impairment phase, but also for other dementias such as vascular and fronto-temporal dementia, and was found to be independent of literacy, education and immigrant status. Lifelong bilingualism represents a powerful cognitive reserve delaying the onset of dementia by approximately 4 years. As to the causal mechanism, because speaking more than one language heavily relies upon executive control and attention, brain systems handling these functions are more developed in bilinguals resulting in increases of gray and white matter densities that may help protect from dementia onset. These neurocognitive benefits are even more prominent when second language proficiency and exposure are kept high throughout life.

Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis.

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Nidos, Andreas; Kasselimis, Dimitrios S; Simos, Panagiotis G; Rentzos, Michael; Alexakis, Theodoros; Zalonis, Ioannis; Zouvelou, Vassiliki; Potagas, Constantin; Evdokimidis, Ioannis; Woolley, Susan C

2016-01-01

There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB). Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%. We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed. © 2015 S. Karger AG, Basel.

A novel network analysis approach reveals DNA damage, oxidative stress and calcium/cAMP homeostasis-associated biomarkers in frontotemporal dementia

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Ferrari, Raffaele; Graziano, Francesca; Novelli, Valeria; Rossi, Giacomina; Galimberti, Daniela; Rainero, Innocenzo; Benussi, Luisa; Nacmias, Benedetta; Bruni, Amalia C.; Cusi, Daniele; Salvi, Erika; Borroni, Barbara; Grassi, Mario

2017-01-01

Frontotemporal Dementia (FTD) is the form of neurodegenerative dementia with the highest prevalence after Alzheimer’s disease, equally distributed in men and women. It includes several variants, generally characterized by behavioural instability and language impairments. Although few mendelian genes (MAPT, GRN, and C9orf72) have been associated to the FTD phenotype, in most cases there is only evidence of multiple risk loci with relatively small effect size. To date, there are no comprehensive studies describing FTD at molecular level, highlighting possible genetic interactions and signalling pathways at the origin FTD-associated neurodegeneration. In this study, we designed a broad FTD genetic interaction map of the Italian population, through a novel network-based approach modelled on the concepts of disease-relevance and interaction perturbation, combining Steiner tree search and Structural Equation Model (SEM) analysis. Our results show a strong connection between Calcium/cAMP metabolism, oxidative stress-induced Serine/Threonine kinases activation, and postsynaptic membrane potentiation, suggesting a possible combination of neuronal damage and loss of neuroprotection, leading to cell death. In our model, Calcium/cAMP homeostasis and energetic metabolism impairments are primary causes of loss of neuroprotection and neural cell damage, respectively. Secondly, the altered postsynaptic membrane potentiation, due to the activation of stress-induced Serine/Threonine kinases, leads to neurodegeneration. Our study investigates the molecular underpinnings of these processes, evidencing key genes and gene interactions that may account for a significant fraction of unexplained FTD aetiology. We emphasized the key molecular actors in these processes, proposing them as novel FTD biomarkers that could be crucial for further epidemiological and molecular studies. PMID:29020091

A novel network analysis approach reveals DNA damage, oxidative stress and calcium/cAMP homeostasis-associated biomarkers in frontotemporal dementia.

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Fernando Palluzzi

Full Text Available Frontotemporal Dementia (FTD is the form of neurodegenerative dementia with the highest prevalence after Alzheimer's disease, equally distributed in men and women. It includes several variants, generally characterized by behavioural instability and language impairments. Although few mendelian genes (MAPT, GRN, and C9orf72 have been associated to the FTD phenotype, in most cases there is only evidence of multiple risk loci with relatively small effect size. To date, there are no comprehensive studies describing FTD at molecular level, highlighting possible genetic interactions and signalling pathways at the origin FTD-associated neurodegeneration. In this study, we designed a broad FTD genetic interaction map of the Italian population, through a novel network-based approach modelled on the concepts of disease-relevance and interaction perturbation, combining Steiner tree search and Structural Equation Model (SEM analysis. Our results show a strong connection between Calcium/cAMP metabolism, oxidative stress-induced Serine/Threonine kinases activation, and postsynaptic membrane potentiation, suggesting a possible combination of neuronal damage and loss of neuroprotection, leading to cell death. In our model, Calcium/cAMP homeostasis and energetic metabolism impairments are primary causes of loss of neuroprotection and neural cell damage, respectively. Secondly, the altered postsynaptic membrane potentiation, due to the activation of stress-induced Serine/Threonine kinases, leads to neurodegeneration. Our study investigates the molecular underpinnings of these processes, evidencing key genes and gene interactions that may account for a significant fraction of unexplained FTD aetiology. We emphasized the key molecular actors in these processes, proposing them as novel FTD biomarkers that could be crucial for further epidemiological and molecular studies.

Alzheimer and vascular dementia in the elderly patients.

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Seetlani, Naresh Kumar; Kumar, Narindar; Imran, Khalid; Ali, Asif; Shams, Nadia; Sheikh, Taha

2016-01-01

To find out the frequency of Alzheimer's and Vascular dementia in the elderly patients. This cross sectional descriptive study was conducted in Department of Medicine, Ziauddin Hospital Karachi from 1 st October 2013 to 31 st March 2014. Patients with symptoms of dementia for more than 6 months duration, and Mini Mental State Examination score dementia were assessed for duration of symptoms. Patients underwent CT scan of brain. Patients with generalized atrophy of brain on CT scanning of brain were labeled as Alzheimer's dementia, while patients with ischemic or hemorrhagic stroke on CT scan of brain were labeled as vascular dementia. Four hundred twenty two patients were included in this study. There were 232 (54.98 %) male and 190 (45.02 %) were female. The mean age ± SD of the patients was 72.58±5.34 years (95% CI: 72.07 to 73.09), similarly average duration of symptoms was 10.14±2.85 months. About 18.96% of patients were illiterate, 32.23% were matric, 28.44% were intermediate and 20.33% were graduate and post graduate. Hypertension and diabetes were the commonest co-morbid i.e. 81.3% and 73.7%, hyperlipedimia and smoking were 38.2% and 45% respectively. Frequency of Alzheimer's disease and vascular dementia in the elderly was observed in 3.79% (16/422) and 2.61% (11/422) cases. A good number of patients, 27 out of 422, in this hospital based study were suffering from Alzheimer's disease and vascular dementia. Early detection and prompt treatment can reduce the burden of the disease in our population.

Behavioral correlates of cerebrospinal fluid amino acid and biogenic amine neurotransmitter alterations in dementia.

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Vermeiren, Yannick; Le Bastard, Nathalie; Van Hemelrijck, An; Drinkenburg, Wilhelmus H; Engelborghs, Sebastiaan; De Deyn, Peter P

2013-09-01

Behavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates of BPSD to provide further insight into its underlying neurochemical pathophysiological mechanisms. Patients with probable Alzheimer's disease (AD; n = 202), probable AD with cerebrovascular disease (n = 37), probable frontotemporal dementia (FTD; n = 32), and probable dementia with Lewy bodies (DLB; n = 26) underwent behavioral assessment and lumbar puncture. CSF levels of six amino acids and several biogenic amines and metabolites were analyzed using ultraperformance liquid chromatography with fluorescence detection and reversed-phase high-performance liquid chromatography with fluorescence detection. In the AD patients, CSF homovanillic acid/5-hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with anxieties/phobias, whereas CSF levels of taurine correlated negatively with depression and behavioral disturbances in general. In FTD patients, CSF levels of glutamate correlated negatively with verbally agitated behavior. In DLB patients, CSF levels of HVA correlated negatively with hallucinations. Several neurotransmitter systems can be linked to one specific behavioral syndrome depending on the dementia subtype. In addition to biogenic amines and metabolites, amino acids seem to play a major role in the neurochemical etiology of BPSD as well. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Possibility of objective diagnosis in patients with mild Alzheimer-type dementia

International Nuclear Information System (INIS)

Kodama, Naoki; Shimada, Tetsuo; Kaeriyama, Tomoharu; Kaneko, Tomoyuki; Fukumoto, Ichiro; Okamoto, Koichiro

2003-01-01

In this study, patients with mild Alzheimer-type dementia were compared with healthy elderly volunteers by means of 12 features to evaluate the possibility of objective diagnosis of mild dementia. The subjects included 9 patients with questionable dementia, 14 patients with mild dementia, and 30 healthy elderly volunteers as controls. In addition, the 23 patients with questionable or mild dementia were included in the mild Alzheimer-type dementia group. A statistically significant difference was found between the mild Alzheimer-type dementia group and the healthy volunteers in 4 of the 10 textural features. Discriminant analysis using these 4 features demonstrated a sensitivity of 87.0% and a specificity of 66.7%. These results suggest the possibility of objective diagnosis in patients with mild Alzheimer-type dementia. (author)

Computer-assisted diagnostic system for neurodegenerative dementia using brain SPECT and 3D-SSP

International Nuclear Information System (INIS)

Ishii, Kazunari; Kanda, Tomonori; Uemura, Takafumi; Miyamoto, Naokazu; Yoshikawa, Toshiki; Shimada, Kenichi; Ohkawa, Shingo; Minoshima, Satoshi

2009-01-01

To develop a computer-assisted automated diagnostic system to distinguish among Alzheimer disease (AD), dementia with Lewy bodies (DLB), and other degenerative disorders in patients with mild dementia. Single photon emission computed tomography (SPECT) images with injection of N-Isopropyl-p-[ 123 I]iodoamphetamine (IMP) were obtained from patients with mild degenerative dementia. First, datasets from 20 patients mild AD, 15 patients with dementia with DLB, and 17 healthy controls were used to develop an automated diagnosing system based on three-dimensional stereotactic surface projections (3D-SSP). AD- and DLB-specific regional templates were created using 3D-SSP, and critical Z scores in the templates were established. Datasets from 50 AD patients, 8 DLB patients, and 10 patients with non-AD/DLB type degenerative dementia (5 with frontotemporal dementia and 5 with progressive supranuclear palsy) were then used to test the diagnostic accuracy of the optimized automated system in comparison to the diagnostic interpretation of conventional IMP-SPECT images. These comparisons were performed to differentiate AD and DLB from non-AD/DLB and to distinguish AD from DLB. A receiver operating characteristic (ROC) analysis was performed. The area under the ROC curve (Az) and the accuracy of the automated diagnosis system were 0.89 and 82%, respectively, for AD/DLB vs. non-AD/DLB patients, and 0.70 and 65%, respectively, for AD vs. DLB patients. The mean Az and the accuracy of the visual inspection were 0.84 and 77%, respectively, for AD/DLB vs. non-AD/DLB patients, and 0.70 and 65%, respectively, for AD vs. DLB patients. The mean Az and the accuracy of the combination of visual inspection and this system were 0.96 and 91%, respectively, for AD/DLB vs. non-AD/DLB patients, and 0.70 and 66%, respectively, for AD vs. DLB patients. The system developed in the present study achieved as good discrimination of AD, DLB, and other degenerative disorders in patients with mild dementia

Evaluative Conditioning with Facial Stimuli in Dementia Patients

OpenAIRE

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 chan...

99mTc-Hexamethyl Propyleneamine Oxime Brain Perfusion Single Photon Emission Computed Tomography in Characterization of Dementia: An Initial Experience in Indian Clinical Practice

International Nuclear Information System (INIS)

Santra, Amburanjan; Sinha, Gaurav Kumar; Neogi, Rajarshi; Thukral, Ramesh Kumar

2014-01-01

There is a growing health burden in developing countries due to recent trends of increasing incidence of neurodegenerative diseases. To reduce the healthcare cost and effective management of dementia illness, early diagnosis, accurate differentiation and their progression assessment is becoming crucially important. We are utilizing 99m Tc-d, l-hexamethyl propyleneamine oxime (HMPAO) brain perfusion single photon emission computed tomography (SPECT) to characterize dementia on the basis of perfusion patterns and observed significant improvement in their management. Eleven patients (median age of 60 years range of 53-83 years) with clinical suspicion of dementia underwent 99m Tc-HMPAO brain perfusion SPECT. SPECT-computed tomography acquisition done, data are reconstructed, reviewed in three view and further processed in “neurogam” to get voxel based analysis and the comparison with age based normal database and surface mapping. Final diagnosis was done with clinical correlation. Four patients are diagnosed as Alzheimer's disease, two as frontotemporal dementia, one as dementia of Lewy bodies, two as vascular dementia and two as pseudodementia. All imaging findings are well-correlated with clinical background. Brain perfusion SPECT with HMPAO was very helpful to us in characterizing the patients of dementia by its perfusion pattern

Music Therapy with Ethnic Music for Dementia Patients

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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.