Aphasic variant of Alzheimer disease

Objective: To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD. Methods: A total of 139 prospectively enrolled participants with a root diagnosis of PPA constituted the reference set. Those with autopsy or biomarker evidence of AD, and who had been evaluated at mild disease stages (Aphasia Quotient$85), were included (n5 19). All had quantitative language testing and APOE genotyping. Fifteen had MRI morphometry. Results: Impaired word-finding was the universal presenting complaint in the aphasic AD group. PPA clinical subtype was logopenic (n 5 13) and agrammatic (n 5 6). Fluency, repetition, naming, and grammaticality ranged from preserved to severely impaired. All had relative preservation of word comprehension. Eight of the 15 aphasic participants with AD showed no appreciable cortical atrophy at the individual level on MRI. As a group, atrophy was asymmetrically concentrated in the left perisylvian cortex. APOE e4 frequency was not elevated. Conclusions: There is a close, but not obligatory, association between logopenic PPA and AD. No language measure, with the possible exception of word comprehension, can confirm or exclude AD in PPA. Biomarkers are therefore essential for diagnosis. Asymmetry of cortical atrophy and normal APOE e4 prevalence constitute deviations from typical AD. These and additional neuropathologic features suggest that AD has biological subtypes, one of which causes PPA. Better appreciation of this fact should promote the inclusion of individuals with PPA and positive AD biomarkers into relevant clinical trials. Neurology® 2016;87:1–7 GLOSSARY AD 5 Alzheimer disease; AQ 5 aphasia quotient; FDR 5 false discovery rate; FTLD 5 frontotemporal lobar degeneration; NAT 5 Northwestern Anagram Test; NAVS-SPPT 5 Sentence Production Priming Test of the Northwestern Assessment of Verbs and Sentences; NFT 5 neurofibrillary tangles; PPA 5 primary progressive aphasia; PPA-G 5 primary progressive aphasia agrammatic subtype; PPA-L 5 primary progressive aphasia logopenic subtype; PPA-S 5 primary progressive aphasia semantic subtype; SOB 5 sum of boxes; WAB-R 5 Western Aphasia Battery–Revised; WPM 5 words per minute. Primary progressive aphasia (PPA) is diagnosed when language impairment arises in relative isolation and progresses to become the primary obstacle to daily functioning. Frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) are its most common neuropathologic correlates. The primary pathology is frequently FTLD-tau in agrammatic subtypes (PPA-G), FTLD-TDP in semantic subtypes (PPA-S), and AD in logopenic subtypes (PPA-L). The goal of this report is to characterize the features of PPA associated with AD. Previous investigations were based on samples of convenience with aphasias of variable severity and language testing of limited coverage, especially in the domain of grammar. The current report is based on 19 individuals with a clinical diagnosis of PPA and with postmortem verification or amyloid-PET scans consistent with AD pathology. All participants were enrolled into a prospective project where language measures are quantitatively and uniformly assessed and where cortical morphometry is used to identify regions of peak atrophy. Only participants initially studied at mild stages of aphasia From the Cognitive Neurology and Alzheimer’s Disease Center (E.R., J.S., B.R., A.M., C.K.T., S.W., M.-M.M.) and Departments of Psychiatry and Behavioral Sciences (D.C., S.W.), Neurology (C.K.T., M.-M.M.), and Pathology (E.H.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Banner Alzheimer’s Institute (K.C.), Phoenix, AZ; and Department of Communication Sciences Disorders (C.K.T.), Northwestern University, Evanston, IL. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2016 American Academy of Neurology 1 a 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Published Ahead of Print on August 26, 2016 as 10.1212/WNL.0000000000003165