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.

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.

Fig 1

Cerebrovascular disease pathology scoring system.

Fig 2

Distribution of pathology scores among 79 autopsy cases: (A) Braak and Braak stage (0–VI), (B) Consortium to Establish a Registry for Alzheimer Disease (CERAD) neuritic plaque score (0–3), (C) cerebrovascular parenchymal pathology scores (CVDPS; 0–300), (D) cystic infarct score (0–100), (E) lacunar infarct score (0–100), and (F) microinfarct score (0–100).

Fig 3

Distribution of cerebrovascular parenchymal pathology scores (CVDPS) and infarct subscores by last clinical diagnosis: minimum, first quartile q1, median, third quartile q3, maximum. AD = Alzheimer’s disease; IVD = ischemic vascular dementia.

Fig 4

Distribution of hippocampal sclerosis scores by diagnosis at last clinic visit. (Ischemic vascular dementia [IVD] includes cognitively impaired cerebrovascular disease [CI-CVD] and subcortical ischemic vascular dementia [SIVD]; Alzheimer’s disease [AD] includes CI-AD and AD.)