title: Cognitive impact of subcortical vascular and Alzheimer's disease pathology.
abstract: OBJECTIVE
  To assess the interactions among three types of pathology (ie, cerebrovascular disease, hippocampal sclerosis [HS], and Alzheimer's disease [AD]), cognitive status, and apolipoprotein E genotype.
  
  
  METHODS
  We report clinicopathological correlations from 79 autopsy cases derived from a prospective longitudinal study of subcortical ischemic vascular disease and AD.
  
  
  RESULTS
  Thirty percent of the cases had significant cerebrovascular parenchymal pathology scores (CVDPS), 54% had significant AD pathology, and 18% had HS. In an ordinal logistic regression analysis that included interaction terms to assess the effects of each pathological variable when the other variables are interpolated to zero, each of the three pathology variables contributed independently to cognitive status: Braak and Braak stage odds ratio (OR) = 2.84 (95% confidence interval, 1.81-4.45), HS score OR = 2.43 (95% confidence interval, 1.01-5.85), and CVDPS OR = 1.02 (95% confidence interval, 1.00-1.04). Only Braak and Braak stage contributed to a global neuropsychological measure of cognitive impairment. Apolipoprotein E4 genotype was associated with Braak and Braak stage (OR, 1.31 [95% confidence interval, 1.03-1.68]), but not CVDPS or HS scores.
  
  
  CONCLUSIONS
  In this convenience sample enriched for subcortical ischemic vascular disease, HS was a common unsuspected neuropathological finding. Apolipoprotein E4 genotype was associated with cerebral amyloid angiopathy, but not HS or arteriosclerosis. When Braak and Braak stage was interpolated to zero, both CVDPS and HS contributed to cognitive impairment. However, advancing stages of AD pathology overwhelmed the effects of CVDPS and HS, to become the major determinant of dementia.
authors.affiliation: Department of Neurology, University of Southern California, Los Angeles, USA. chui@usc.edu
authors.forename: Helena C
authors.initials: HC
authors.lastname: Chui
authors.forename: Chris
authors.initials: C
authors.lastname: Zarow
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.forename: William G
authors.initials: WG
authors.lastname: Ellis
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.forename: Dan
authors.initials: D
authors.lastname: Mungas
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Reed
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.forename: Charles C
authors.initials: CC
authors.lastname: Decarli
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology* / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology* / Q000523:psychology; D015984:Causality; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000473:pathology / Q000523:psychology; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology / Q000473:pathology*; D015897:Comorbidity; D015140:Dementia, Vascular / Q000150:complications / Q000473:pathology* / Q000523:psychology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012598:Sclerosis; D013687:Telencephalon / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D001057:Apolipoproteins E