Characterization of TDP43 protein in primary progressive aphasia (PPA) and frontotemporal dementia (FTD) with Alzheimer disease (AD) pathology

Apathy is prevalent in dementia, such as behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD). As a multidimensional construct, it can be assessed and subsumed under a Dimensional Apathy Framework. A consistent apathy profile in bvFTD and PPA has yet to be established. The aim was to explore apathy profiles and awareness in bvFTD, PPA, and AD. A total of 12 patients with bvFTD, 12 patients with PPA, 28 patients with AD, and 20 matched controls, as well as their informants/carers, were recruited. All participants completed the Dimensional Apathy Scale (DAS), assessing executive, emotional, and initiation apathy subtypes, a 1-dimensional apathy measure, depression measure, and functional and cognitive screens. Apathy subtype awareness was determined through DAS informant/carer and self-rating discrepancy. Apathy profile comparison showed patients with bvFTD had significantly higher emotional apathy than patients with AD ( P < .01) and significantly higher apathy over all subtypes than patients with PPA ( Ps < .05). Additionally, patients with bvFTD had significantly lower awareness for emotional apathy ( P < .01) when compared to patients with AD and PPA. All patient groups had significant global apathy over all subtypes compared to controls. The emergent apathy profile for bvFTD seems to be emotional apathy (indifference or emotional/affective neutrality), with lower self-awareness in this subtype. Further, lower self-awareness for executive apathy (lack of motivation for planning, organization, or attention) differentiates bvFTD from PPA. Future research should investigate the cognitive and neural correlates as well as the practical impact of apathy subtypes.

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TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease

Acta Neuropathologica ◽

10.1007/s00401-010-0681-2 ◽

2010 ◽

Vol 120 (1) ◽

pp. 43-54 ◽

Cited By ~ 46

Author(s):

Eileen H. Bigio ◽

Manjari Mishra ◽

Kimmo J. Hatanpaa ◽

Charles L. White ◽

Nancy Johnson ◽

...

Keyword(s):

Alzheimer Disease ◽

Frontotemporal Dementia ◽

Primary Progressive Aphasia ◽

Progressive Aphasia ◽

Primary Progressive

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The Mini-Mental State Examination in Behavioral Variant Frontotemporal Dementia and Primary Progressive Aphasia

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317507307173 ◽

2008 ◽

Vol 22 (6) ◽

pp. 468-473 ◽

Cited By ~ 34

Author(s):

Jason E. Osher ◽

Alissa H. Wicklund ◽

Alfred Rademaker ◽

Nancy Johnson ◽

Sandra Weintraub

Keyword(s):

Frontotemporal Dementia ◽

Mental State ◽

Mini Mental State Examination ◽

Primary Progressive Aphasia ◽

Behavioral Variant Frontotemporal Dementia ◽

Progressive Aphasia ◽

Primary Progressive ◽

State Examination

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Executive Dysfunction and Behavioral Symptoms Are Associated with Deficits in Instrumental Activities of Daily Living in Frontotemporal Dementia

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000455119 ◽

2017 ◽

Vol 43 (1-2) ◽

pp. 89-99 ◽

Cited By ~ 10

Author(s):

Negar Moheb ◽

Mario F. Mendez ◽

Sarah A. Kremen ◽

Edmond Teng

Keyword(s):

Activities Of Daily Living ◽

Frontotemporal Dementia ◽

Daily Living ◽

Primary Progressive Aphasia ◽

Executive Dysfunction ◽

Behavioral Symptoms ◽

Data Set ◽

Progressive Aphasia ◽

Primary Progressive ◽

Instrumental Activities

Background: Deficits in instrumental activities of daily living (ADLs) may be more prominent in behavioral variant frontotemporal dementia (bvFTD) than in nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) or semantic variant primary progressive aphasia (svPPA). It is uncertain whether frontotemporal dementia (FTD) subgroups exhibit different patterns and/or predictors of functional impairment. Methods: We examined data from participants diagnosed with bvFTD (n = 607), svPPA (n = 132), and nfvPPA (n = 155) who were included in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) and assessed with the Functional Activities Questionnaire (FAQ). Stepwise multiple linear regression analyses were performed to identify associations between FAQ scores and cognitive/behavioral deficits using the NACC UDS neuropsychological testing battery and the Neuropsychiatric Inventory Questionnaire. Results: FAQ scores were higher in bvFTD than svPPA or nfvPPA. Functional deficits across FTD subtypes differed in severity, but not pattern, and were driven by executive dysfunction and behavioral symptoms. Conclusion: Executive dysfunction and behavioral symptoms underlie instrumental ADL deficits in FTD, which are most prominent in bvFTD.

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A patient with agrammatic primary progressive aphasia developing frontotemporal dementia

Acta Neurologica Belgica ◽

10.1007/s13760-015-0446-8 ◽

2015 ◽

Vol 115 (4) ◽

pp. 763-766 ◽

Cited By ~ 1

Author(s):

Fabricio Ferreira de Oliveira ◽

Lucas Amorim Vieira de Barros ◽

Paulo Henrique Ferreira Bertolucci

Keyword(s):

Frontotemporal Dementia ◽

Primary Progressive Aphasia ◽

Progressive Aphasia ◽

Primary Progressive

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Memory Resilience in Alzheimer Disease With Primary Progressive Aphasia

Neurology ◽

10.1212/wnl.0000000000011397 ◽

2021 ◽

Vol 96 (6) ◽

pp. e916-e925

Author(s):

M.-Marsel Mesulam ◽

Christina Coventry ◽

Alan Kuang ◽

Eileen H. Bigio ◽

Qinwen Mao ◽

...

Keyword(s):

Alzheimer Disease ◽

Verbal Memory ◽

Incidental Finding ◽

Primary Progressive Aphasia ◽

Neurofibrillary Degeneration ◽

Progressive Aphasia ◽

Primary Progressive ◽

Language Functions ◽

Link Type ◽

Potential Factors

ObjectiveTo determine whether memory is preserved longitudinally in primary progressive aphasia (PPA) associated with Alzheimer disease (AD) and to identify potential factors that maintain memory despite underlying neurofibrillary degeneration of mediotemporal memory areas.MethodsLongitudinal memory assessment was done in 17 patients with PPA with autopsy or biomarker evidence of AD (PPA-AD) and 14 patients with amnestic dementia of the Alzheimer type with AD at autopsy (DAT-AD).ResultsIn PPA-AD, episodic memory, tested with nonverbal items, was preserved at the initial testing and showed no decline at retesting 2.35 ± 0.78 years later, at which time symptoms had been present for 6.26 ± 2.21 years. In contrast, language functions declined significantly during the same period. In DAT-AD, both verbal memory and language declined with equal severity. Although imaging showed asymmetric left-sided mediotemporal atrophy in PPA-AD, autopsy revealed bilateral hippocampo-entorhinal neurofibrillary degeneration at Braak stages V and VI. Compared to DAT-AD, however, the PPA-AD group had lower incidence of APOE ε4 and of mediotemporal TAR DNA-binding protein 43 (TDP-43) pathology.ConclusionsMemory preservation in PPA is not just an incidental finding at onset but a core feature that persists for years despite the hippocampo-entorhinal AD neuropathology that is as severe as that of DAT-AD. Asymmetry of mediotemporal atrophy and a lesser impact of APOE ε4 and of TDP-43 on the integrity of memory circuitry may constitute some of the factors underlying this resilience. Our results also suggest that current controversies on memory in PPA-AD reflect inconsistencies in the diagnosis of logopenic PPA, the clinical variant most frequently associated with AD.ClinicalTrials.gov IdentifierNCT00537004 and NCT03371706.

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