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Cognitive impact of subcortical vascular and Alzheimer's disease pathology
Author(s) -
Chui Helena C.,
Zarow Chris,
Mack Wendy J.,
Ellis William G.,
Zheng Ling,
Jagust William J.,
Mungas Dan,
Reed Bruce R.,
Kramer Joel H.,
DeCarli Charles C.,
Weiner Michael W.,
Vinters Harry V.
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21009
Subject(s) - cerebral amyloid angiopathy , odds ratio , pathology , apolipoprotein e , alzheimer's disease , dementia , neuropathology , confidence interval , medicine , psychology , disease
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. Interpretation 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. Ann Neurol 2006;60:677–687