Abstract
Objective Methods To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-beta 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) epsilon 4 status was determined using generalized estimating equation models. Results Interpretation Amyloid-beta positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p <0.001). Prevalence of amyloid-beta positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p <0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p <0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE epsilon 4 carriers were more often amyloid-beta positive (58.0%) than noncarriers (35.0%, p <0.001). Autopsy data revealed Alzheimer disease 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%). 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 considered when interpreting amyloid-beta biomarkers in PPA patients. Ann Neurol 2018;84:737-748
Original language | English |
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Pages (from-to) | 729-740 |
Number of pages | 12 |
Journal | Annals of Neurology |
Volume | 84 |
Issue number | 5 |
DOIs | |
Publication status | Published - Nov 2018 |
Keywords
- ALZHEIMER-DISEASE
- FRONTOTEMPORAL PATHOLOGY
- NATIONAL INSTITUTE
- PET
- CONSENSUS
- DEMENTIA
- LANGUAGE
- BIOMARKERS
- DIAGNOSIS
- HETEROGENEITY