Purpose of Review: The term primary progressive aphasia (PPA) refers to a diverse group of dementias that present with prominent and early problems with speech and language. They present considerable challenges to clinicians and researchers.Recent Findings: Here, we review critical issues around diagnosis of the three major PPA variants (semantic variant PPA, nonfluent/agrammatic variant PPA, logopenic variant PPA), as well as considering ‘fragmentary’ syndromes. We next consider issues around assessing disease stage, before discussing physiological phenotyping of proteinopathies across the PPA spectrum. We also review evidence for core central auditory impairments in PPA, outline critical challenges associated with treatment, discuss pathophysiological features of each major PPA variant, and conclude with thoughts on key challenges that remain to be addressed.Summary: New findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies.

Here, we review recent progress in the diagnosis and management of primary progressive aphasia—the language-led dementias. We pose six key unanswered questions that challenge current assumptions and highlight the unresolved difficulties that surround these diseases. How many syndromes of primary progressive aphasia are there—and is syndromic diagnosis even useful? Are these truly ‘language-led’ dementias? How can we diagnose (and track) primary progressive aphasia better? Can brain pathology be predicted in these diseases? What is their core pathophysiology? In addition, how can primary progressive aphasia best be treated? We propose that pathophysiological mechanisms linking proteinopathies to phenotypes may help resolve the clinical complexity of primary progressive aphasia, and may suggest novel diagnostic tools and markers and guide the deployment of effective therapies.

Sleep disruption is a key clinical issue in the dementias but the sleep phenotypes of these diseases remain poorly characterised. Here we addressed this issue in a proof-of-principle study of 67 patients representing major syndromes of frontotemporal dementia (FTD) and Alzheimer's disease (AD), in relation to 25 healthy older individuals. We collected reports on clinically-relevant sleep characteristics - time spent overnight in bed, sleep quality, excessive daytime somnolence and disruptive sleep events. Difficulty falling or staying asleep at night and excessive daytime somnolence were significantly more frequently reported for patients with both FTD and AD than healthy controls. On average, patients with FTD and AD retired earlier and patients with AD spent significantly longer in bed overnight than did healthy controls. Excessive daytime somnolence was significantly more frequent in the FTD group than the AD group; AD syndromic subgroups showed similar sleep symptom profiles while FTD subgroups showed more variable profiles. Sleep disturbance is a significant clinical issue in major FTD and AD variant syndromes and may be even more salient in FTD than AD. These preliminary findings warrant further systematic investigation with electrophysiological and neuroanatomical correlation in major proteinopathies.

Logopenic variant primary progressive aphasia (lvPPA) is the least well defined of the major primary progressive aphasia (PPA) syndromes. We assessed phoneme discrimination in patients with PPA (semantic, nonfluent/agrammatic, and logopenic variants) and typical Alzheimer’s disease, relative to healthy age‐matched participants. The lvPPA group performed significantly worse than all other groups apart from tAD, after adjusting for auditory verbal working memory. In the combined PPA cohort, voxel‐based morphometry correlated phonemic discrimination score with grey matter in left angular gyrus. Our findings suggest that impaired phonemic discrimination may help differentiate lvPPA from other PPA subtypes, with important diagnostic and management implications.

Objectives: We explored whether adapting neuropsychological tests for online administration during the COVID-19 pandemic was feasible for dementia research. Design: We used a longitudinal design for healthy controls, who completed face-to-face assessments 3–4 years before remote assessments. For patients, we used a cross-sectional design, contrasting a prospective remote cohort with a retrospective face-to-face cohort matched for age/education/severity. Setting: Remote assessments were conducted using video-conferencing/online testing platforms, with participants using a personal computer/tablet at home. Face-to-face assessments were conducted in testing rooms at our research centre. Participants: The remote cohort comprised 25 patients (n=8 Alzheimer’s disease (AD); n=3 behavioural variant frontotemporal dementia (bvFTD); n=4 semantic dementia (SD); n=5 progressive non-fluent aphasia (PNFA); n=5 logopenic aphasia (LPA)). The face-to-face patient cohort comprised 64 patients (n=25 AD; n=12 bvFTD; n=9 SD; n=12 PNFA; n=6 LPA). Ten controls who previously participated in face-to-face research also took part remotely. Outcome measures: The outcome measures comprised the strength of evidence under a Bayesian framework for differences in performances between testing environments on general neuropsychological and neurolinguistic measures. Results: There was substantial evidence suggesting no difference across environments in both the healthy control and combined patient cohorts (including measures of working memory, single-word comprehension, arithmetic and naming; Bayes Factors (BF) ₀₁ >3), in the healthy control group alone (including measures of letter/category fluency, semantic knowledge and bisyllabic word repetition; all BF ₀₁ >3), and in the combined patient cohort alone (including measures of working memory, episodic memory, short-term verbal memory, visual perception, non-word reading, sentence comprehension and bisyllabic/trisyllabic word repetition; all BF ₀₁ >3). In the control cohort alone, there was substantial evidence in support of a difference across environments for tests of visual perception (BF ₀₁ =0.0404) and monosyllabic word repetition (BF ₀₁ =0.0487). Conclusions: Our findings suggest that remote delivery of neuropsychological tests for dementia research is feasible.