title: Aphasic variant of Alzheimer disease: Clinical, anatomic, and genetic features.
abstract: 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 (n = 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 = 13) and agrammatic (n = 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 ε4 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 ε4 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.
authors: 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. erogalski@gmail.com.
authors: Emily
authors: E
authors: Rogalski
authors: 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.
authors: Jaiashre
authors: J
authors: Sridhar
authors: 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.
authors: Benjamin
authors: B
authors: Rader
authors: 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.
authors: Adam
authors: A
authors: Martersteck
authors: 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.
authors: Kewei
authors: K
authors: Chen
authors: 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.
authors: Derin
authors: D
authors: Cobia
authors: 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.
authors: Cynthia K
authors: CK
authors: Thompson
authors: 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.
authors: Sandra
authors: S
authors: Weintraub
authors: 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.
authors: Eileen H
authors: EH
authors: Bigio
authors: 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.
authors: M-Marsel
authors: MM
authors: Mesulam
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D018888:Aphasia, Primary Progressive / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging*; D006801:Humans; D007807:Language Tests; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D001057:Apolipoproteins E