Distinct and shared neuropsychiatric phenotypes in FTLD-tauopathies.

Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy.

Differential vulnerability of the dentate gyrus to tauopathies in dementias.

The dentate gyrus (DG), a key hippocampal subregion in memory processing, generally resists phosphorylated tau accumulation in the amnestic dementia of the Alzheimer's type due to Alzheimer's disease (DAT-AD), but less is known about the susceptibility of the DG to other tauopathies. Here, we report stereologic densities of total DG neurons and tau inclusions in thirty-two brains of human participants with autopsy-confirmed tauopathies with distinct isoform profiles-3R Pick's disease (PiD, N = 8), 4R corticobasal degeneration (CBD, N = 8), 4R progressive supranuclear palsy (PSP, N = 8), and 3/4R AD (N = 8). All participants were diagnosed during life with primary progressive aphasia (PPA), an aphasic clinical dementia syndrome characterized by progressive deterioration of language abilities with spared non-language cognitive abilities in early stages, except for five patients with DAT-AD as a comparison group.

Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology.

Quantification of in vivo amyloid and tau PET imaging relationships with postmortem measurements are critical for validating the sensitivity and specificity imaging biomarkers across clinical phenotypes with Alzheimer disease neuropathologic change (ADNC). This study examined the quantitative relationship between regional binding of in vivo F-florbetapir amyloid PET and F-flortaucipir tau PET with postmortem stereological counts of amyloid plaques and neurofibrillary tangles (NFT) in a case of primary progressive aphasia (PPA) with ADNC, where neurodegeneration asymmetrically targets the left hemisphere. Beginning 2 years prior to death, a 63-year-old right-handed man presenting with agrammatic variant PPA underwent a florbetapir and flortaucpir PET scan, and neuropsychological assessments and magnetic resonance imaging sessions every 6 months.

Eye movements as a measure of word comprehension deficits in primary progressive aphasia.

Introduction: Eye movement studies can uncover subtle aspects of language processing impairment in individuals with primary progressive aphasia (PPA), who may have difficulty understanding words. This study examined eye movement patterns on a word-object matching task in response to varying levels of word-knowledge in PPA.

Methods: Participants with semantic and non-semantic PPA completed an object-matching task, where a word was presented and participants then selected the corresponding pictured object from an array.

Neuropathological fingerprints of survival, atrophy and language in primary progressive aphasia.

Primary progressive aphasia is a neurodegenerative disease that selectively impairs language without equivalent impairment of speech, memory or comportment. In 118 consecutive autopsies on patients with primary progressive aphasia, primary diagnosis was Alzheimer's disease neuropathological changes (ADNC) in 42%, corticobasal degeneration or progressive supranuclear palsy neuropathology in 24%, Pick's disease neuropathology in 10%, transactive response DNA binding proteinopathy type A [TDP(A)] in 10%, TDP(C) in 11% and infrequent entities in 3%. Survival was longest in TDP(C) (13.

The Reliability of Telepractice Administration of the Western Aphasia Battery-Revised in Persons With Primary Progressive Aphasia.

Purpose: The use of telepractice in the field of communication disorders offers an opportunity to provide care for those with primary progressive aphasia (PPA). The Western Aphasia Battery-Revised (WAB-R) is used for differential diagnosis, to assess severity of aphasia, and to identify a language profile of strengths and challenges. Telehealth administration of the WAB-R is supported for those with chronic aphasia due to stroke but has not yet been systematically explored in neurodegenerative dementia syndromes.

Communication Partner Engagement: A Relevant Factor for Functional Outcomes in Speech-Language Therapy for Aphasic Dementia.

Objectives: Previous reports established the feasibility of a telehealth model for delivering speech-language therapy via Internet videoconferencing, which connects individuals with primary progressive aphasia (PPA) to an expert speech and language pathologist for treatment. This study reports feasibility of the same telehealth intervention in a larger set of progressive aphasia participants and explores factors potentially influencing functional intervention outcomes.

Methods: Participants with PPA or progressive aphasia in the context of a neurodegenerative dementia syndrome and their communication partners were enrolled into an 8-session intervention, with 3 evaluations (baseline, 2 months, and 6 months postenrollment).

Relationships among tau burden, atrophy, age, and naming in the aphasic variant of Alzheimer's disease.

Introduction: Examination of pathologic, anatomic, and cognitive relationships has been limited in primary progressive aphasia (PPA) with underlying Alzheimer's disease (AD) neuropathology.

Methods: Spatial relationships between tau positron emission tomography (PET), cortical thickness, age, and naming on the Boston Naming Test (BNT) in PPA with biomarker evidence of AD (PPA-AD) were examined.

Results: Higher tau PET burden was associated with atrophy and younger age.

Functional decline in the aphasic variant of Alzheimer's disease.

Introduction: Primary progressive aphasia (PPA) is a clinical dementia syndrome associated with frontotemporal lobar degeneration (FTLD) or Alzheimer's disease (AD). Impairment in activities of daily living is essential for dementia diagnosis, yet less is known about the neuropathologic impact on functional decline in PPA, especially over time.

Methods: Activities of Daily Living Questionnaire (ADLQ) ratings were compared by suspected underlying pathology between 17 PPA and 11 PPA participants at 6-month intervals for 2 years using a linear mixed-effects model.

Memory Resilience in Alzheimer Disease With Primary Progressive Aphasia.

Objective: To 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.

Methods: Longitudinal 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).

Results: In PPA-AD, episodic memory, tested with nonverbal items, was preserved at the initial testing and showed no decline at retesting 2.

Nosology of Primary Progressive Aphasia and the Neuropathology of Language.

Primary progressive aphasia (PPA) is a dementia syndrome associated with several neuropathologic entities, including Alzheimer's disease (AD) and all major forms of frontotemporal lobar degeneration (FTLD). It is classified into subtypes defined by the nature of the language domain that is most impaired. The asymmetric neurodegeneration of the hemisphere dominant for language (usually left) is one consistent feature of all PPA variants.

Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer's disease.

The neurofibrillary tangles (NFT) and amyloid-ß plaques (AP) that comprise Alzheimer's disease (AD) neuropathology are associated with neurodegeneration and microglial activation. Activated microglia exist on a dynamic spectrum of morphologic subtypes that include resting, surveillant microglia capable of converting to activated, hypertrophic microglia closely linked to neuroinflammatory processes and AD neuropathology in amnestic AD. However, quantitative analyses of microglial subtypes and neurons are lacking in non-amnestic clinical AD variants, including primary progressive aphasia (PPA-AD).

Familial language network vulnerability in primary progressive aphasia.

Objective: To investigate evidence of the potential role of early cortical vulnerability in the development of primary progressive aphasia (PPA).

Method: A woman with a diagnosis of PPA and her 9 adult siblings, 7 with developmental language disabilities, underwent neuropsychological testing, structural MRI, and resting-state fMRI. Whole-exome sequencing was conducted for genes associated with dyslexia or with neurodegenerative dementia.

Montreal Cognitive Assessment (MoCA) Performance and Domain-Specific Index Scores in Amnestic Aphasic Dementia.

Objective: The Montreal Cognitive Assessment (MoCA) is a popular and simple-to-administer screening instrument to detect cognitive impairment. The MoCA generates a total score and six domain-specific index scores: (1) Memory, (2) Executive Functioning, (3) Attention, (4) Language, (5) Visuospatial, and (6) Orientation. It is unclear whether these MoCA scores can differentiate between distinct clinical dementia syndromes.

Differential neurocognitive network perturbation in amnestic and aphasic Alzheimer disease.

Objective: To determine if Alzheimer disease (AD) is associated with aphasic rather than amnestic dementias in certain circumstances related in part to perturbations in different networks.

Methods: Three groups were investigated: 14 participants suspected of having the neuropathology of AD based on clinically diagnosed amnestic dementia of the Alzheimer type (DAT), 26 individuals with primary progressive aphasia (PPA) with either a positive F-florbetapir amyloid PET scan or confirmed AD at autopsy, and 26 neurologically intact controls. The groups were compared using rs-fMRI.

is a correlate of phenotypic heterogeneity in Alzheimer disease in a national cohort.

Objective: To compare the proportion of ε4 genotype carriers in aphasic vs amnestic variants of Alzheimer disease (AD).

Method: The proportion of ε4 carriers was compared among the following 3 groups: (1) 42 patients with primary progressive aphasia (PPA) and AD pathology (PPA/AD) enrolled in the Northwestern Alzheimer Disease Center Clinical Core; (2) 1,418 patients with autopsy-confirmed AD and amnestic dementia of the Alzheimer type (DAT/AD); and (3) 2,608 cognitively normal controls (NC). The latter 2 groups were compiled from the National Alzheimer Coordinating Center database.

Neuropathologic basis of in vivo cortical atrophy in the aphasic variant of Alzheimer's disease.

The neuropathologic basis of in vivo cortical atrophy in clinical dementia syndromes remains poorly understood. This includes primary progressive aphasia (PPA), a language-based dementia syndrome characterized by asymmetric cortical atrophy. The neurofibrillary tangles (NFTs) and amyloid-ß plaques (APs) of Alzheimer's disease (AD) can cause PPA, but a quantitative investigation of the relationships between NFTs, APs and in vivo cortical atrophy in PPA-AD is lacking.