title: Differentiating cognitive impairment due to corticobasal degeneration and Alzheimer disease.
abstract: OBJECTIVE
  To identify clinical features that reliably differentiate individuals with cognitive impairment due to corticobasal degeneration (CBD) and Alzheimer disease (AD).
  
  
  METHODS
  Clinical features were compared between individuals with autopsy-proven CBD (n = 17) and AD (n = 16). All individuals presented with prominent cognitive complaints and were evaluated annually with semistructured interviews, detailed neurologic examinations, and neuropsychological testing.
  
  
  RESULTS
  Substantial overlap was observed between individuals with dementia due to CBD and AD concerning presenting complaints, median (range) duration of symptoms before assessment (CBD = 3.0 [0-5.0] years, AD = 2.5 [0-8.0] years;p= 0.96), and median (range) baseline dementia severity (Clinical Dementia Rating Sum of Boxes: CBD = 3.5 [0-12.0], AD = 4.25 [0.5-9.0],p= 0.49). Subsequent emergence of asymmetric motor/sensory signs, hyperreflexia, gait abnormalities, parkinsonism, falls, urinary incontinence, and extraocular movement abnormalities identified individuals with CBD, with ≥3 discriminating features detected in 80% of individuals within 3.1 years (95% confidence interval 2.9-3.3) of the initial assessment. Individuals with CBD exhibited accelerated worsening of illness severity and declines in episodic memory, executive functioning, and letter fluency. Semiquantitative pathologic assessment revealed prominent tau pathology within the frontal and parietal lobes of CBD cases. Comorbid AD neuropathologic change was present in 59% (10 of 17) of CBD cases but did not associate with the clinical phenotype, rate of dementia progression, or dementia duration.
  
  
  CONCLUSIONS
  CBD may mimic AD dementia early in its disease course. Interval screening for discriminating clinical features may improve antemortem diagnosis in individuals with CBD and prominent cognitive symptoms.
authors.affiliation: From the Charles F. and Joanne Knight Alzheimer Disease Research Center (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), Department of Neurology (G.S.D., T.S.L., J.H., C.M.R., N.J.C., J.C.C.), Division of Biostatistics (E.A.G.), and Department of Pathology and Immunology (N.J.C.), Washington University School of Medicine (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), St. Louis, MO; Ajou University School of Medicine (T.S.L.), Suwon, Republic of Korea; and Icahn School of Medicine at Mount Sinai (A.M.G.), New York, NY.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Day
authors.affiliation: From the Charles F. and Joanne Knight Alzheimer Disease Research Center (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), Department of Neurology (G.S.D., T.S.L., J.H., C.M.R., N.J.C., J.C.C.), Division of Biostatistics (E.A.G.), and Department of Pathology and Immunology (N.J.C.), Washington University School of Medicine (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), St. Louis, MO; Ajou University School of Medicine (T.S.L.), Suwon, Republic of Korea; and Icahn School of Medicine at Mount Sinai (A.M.G.), New York, NY.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Lim
authors.affiliation: From the Charles F. and Joanne Knight Alzheimer Disease Research Center (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), Department of Neurology (G.S.D., T.S.L., J.H., C.M.R., N.J.C., J.C.C.), Division of Biostatistics (E.A.G.), and Department of Pathology and Immunology (N.J.C.), Washington University School of Medicine (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), St. Louis, MO; Ajou University School of Medicine (T.S.L.), Suwon, Republic of Korea; and Icahn School of Medicine at Mount Sinai (A.M.G.), New York, NY.
authors.forename: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.affiliation: From the Charles F. and Joanne Knight Alzheimer Disease Research Center (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), Department of Neurology (G.S.D., T.S.L., J.H., C.M.R., N.J.C., J.C.C.), Division of Biostatistics (E.A.G.), and Department of Pathology and Immunology (N.J.C.), Washington University School of Medicine (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), St. Louis, MO; Ajou University School of Medicine (T.S.L.), Suwon, Republic of Korea; and Icahn School of Medicine at Mount Sinai (A.M.G.), New York, NY.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.affiliation: From the Charles F. and Joanne Knight Alzheimer Disease Research Center (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), Department of Neurology (G.S.D., T.S.L., J.H., C.M.R., N.J.C., J.C.C.), Division of Biostatistics (E.A.G.), and Department of Pathology and Immunology (N.J.C.), Washington University School of Medicine (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), St. Louis, MO; Ajou University School of Medicine (T.S.L.), Suwon, Republic of Korea; and Icahn School of Medicine at Mount Sinai (A.M.G.), New York, NY.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grant
authors.affiliation: From the Charles F. and Joanne Knight Alzheimer Disease Research Center (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), Department of Neurology (G.S.D., T.S.L., J.H., C.M.R., N.J.C., J.C.C.), Division of Biostatistics (E.A.G.), and Department of Pathology and Immunology (N.J.C.), Washington University School of Medicine (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), St. Louis, MO; Ajou University School of Medicine (T.S.L.), Suwon, Republic of Korea; and Icahn School of Medicine at Mount Sinai (A.M.G.), New York, NY.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.affiliation: From the Charles F. and Joanne Knight Alzheimer Disease Research Center (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), Department of Neurology (G.S.D., T.S.L., J.H., C.M.R., N.J.C., J.C.C.), Division of Biostatistics (E.A.G.), and Department of Pathology and Immunology (N.J.C.), Washington University School of Medicine (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), St. Louis, MO; Ajou University School of Medicine (T.S.L.), Suwon, Republic of Korea; and Icahn School of Medicine at Mount Sinai (A.M.G.), New York, NY.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: From the Charles F. and Joanne Knight Alzheimer Disease Research Center (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), Department of Neurology (G.S.D., T.S.L., J.H., C.M.R., N.J.C., J.C.C.), Division of Biostatistics (E.A.G.), and Department of Pathology and Immunology (N.J.C.), Washington University School of Medicine (G.S.D., T.S.L., J.H., A.M.G., E.A.G., C.M.R., N.J.C., J.C.M.), St. Louis, MO; Ajou University School of Medicine (T.S.L.), Suwon, Republic of Korea; and Icahn School of Medicine at Mount Sinai (A.M.G.), New York, NY. jcmorris@wustl.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D001479:Basal Ganglia / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000209:etiology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000150:complications*; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D018709:Statistics, Nonparametric