Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia

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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Multidimensional Apathy in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia, and Alzheimer Disease

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/0891988720924716 ◽

2020 ◽

pp. 089198872092471

Author(s):

Ratko Radakovic ◽

Shuna Colville ◽

Denise Cranley ◽

John M. Starr ◽

Suvankar Pal ◽

...

Keyword(s):

Alzheimer Disease ◽

Frontotemporal Dementia ◽

Primary Progressive Aphasia ◽

Future Research ◽

Self Awareness ◽

Behavioral Variant Frontotemporal Dementia ◽

Progressive Aphasia ◽

Primary Progressive ◽

Patient Groups ◽

Rating Discrepancy

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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Clinical marker for Alzheimer disease pathology in logopenic primary progressive aphasia

Neurology ◽

10.1212/wnl.0000000000004034 ◽

2017 ◽

Vol 88 (24) ◽

pp. 2276-2284 ◽

Cited By ~ 45

Author(s):

Lucia A.A. Giannini ◽

David J. Irwin ◽

Corey T. McMillan ◽

Sharon Ash ◽

Katya Rascovsky ◽

...

Keyword(s):

Alzheimer Disease ◽

Digit Span ◽

Primary Progressive Aphasia ◽

Angular Gyrus ◽

Lexical Retrieval ◽

Central Feature ◽

Retrospective Case ◽

Progressive Aphasia ◽

Primary Progressive ◽

Sentence Repetition

Objective:To determine whether logopenic features of phonologic loop dysfunction reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia (PPA).Methods:We performed a retrospective case-control study of 34 patients with PPA with available autopsy tissue. We compared baseline and longitudinal clinical features in patients with primary AD neuropathology to those with primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in pathology-defined groups using postmortem neuropathologic data.Results:A total of 19/34 patients had primary AD pathology and 15/34 had non-AD pathology (13 frontotemporal lobar degeneration, 2 Lewy body disease). A total of 16/19 (84%) patients with AD had a logopenic spectrum phenotype; 5 met published criteria for the logopenic variant (lvPPA), 8 had additional grammatical or semantic deficits (lvPPA+), and 3 had relatively preserved sentence repetition (lvPPA−). Sentence repetition was impaired in 68% of patients with PPA with AD pathology; forward digit span (DF) was impaired in 90%, substantially higher than in non-AD PPA (33%, p < 0.01). Lexical retrieval difficulty was common in all patients with PPA and did not discriminate between groups. Compared to non-AD, PPA with AD pathology had elevated microscopic neurodegenerative pathology in the superior/midtemporal gyrus, angular gyrus, and midfrontal cortex (p < 0.01). Low DF scores correlated with high microscopic pathologic burden in superior/midtemporal and angular gyri (p ≤ 0.03).Conclusions:Phonologic loop dysfunction is a central feature of AD-associated PPA and specifically correlates with temporoparietal neurodegeneration. Quantitative measures of phonologic loop function, combined with modified clinical lvPPA criteria, may help discriminate AD-associated PPA.

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