Primary progressive aphasia: a clinical approach

This work was supported by the Alzheimer’s Society (AS-PG-16-007), the National Institute for Health Research University College London Hospitals Biomedical Research Centre and the UCL Leonard Wolfson Experimental Neurology Centre (PR/ylr/18575). Individual authors were supported by the Leonard Wolfson Foundation (Clinical Research Fellowship to CRM), the National Institute for Health Research (NIHR Doctoral Training Fellowship to AV), the National Brain Appeal–Frontotemporal Dementia Research Fund (CNC) and the Medical Research Council (PhD Studentships to CJDH and RLB, MRC Research Training Fellowship to PDF, MRC Clinician Scientist to JDR). MNR and NCF are NIHR Senior Investigators. SJC is supported by Grants from ESRC-NIHR (ES/L001810/1), EPSRC (EP/M006093/1) and Wellcome Trust (200783). JDW was supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (091673/Z/10/Z)

Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia

OBJECTIVE: To estimate the prevalence of amyloid-positivity, defined by PET/CSF biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. METHODS: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n=443], non-fluent [nfvPPA, n=333], semantic [svPPA, n=401] and mixed/unclassifiable [PPA-M/U, n=74] variants of PPA) from 36 centers, with a measure of amyloid-β pathology (CSF [n=600]), PET [n=366] and/or autopsy [n=378]) available. The estimated prevalence of amyloid-positivity according to PPA variant, age and apolipoprotein E (APOE) ε4 status was determined using generalized estimating equation models. RESULTS: Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%) (p<0.001). Prevalence of amyloid-β positivity increased with age in nfvPPA (from 10% at age 50 to 27% at age 80, p<0.01) and svPPA (from 6% at age 50 to 32% at age 80, p<0.001), but not in lvPPA (p=0.94). Across PPA variants, APOE ε4 carriers were more often amyloid-β positive (58.0%) than non-carriers (35.0%, p<0.001). Autopsy data revealed Alzheimer's disease (AD) pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration - TDP-43 in svPPA (80%) and frontotemporal lobar degeneration-TDP-43/tau in nfvPPA (64%). INTERPRETATION: This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and APOE genotype should be taken into account when interpreting Aβ biomarkers in PPA patients. This article is protected by copyright. All rights reserved