Aggregate effects of vascular risk factors on cerebrovascular changes in autopsy-confirmed Alzheimer's disease

Abstract

We examined the relationships of antemortem vascular risk factors to postmortem cerebrovascular and Alzheimer's disease (AD) pathologies. Eighty-four AD patients underwent an assessment of vascular risk (blood pressure, cholesterol, smoking, cardiovascular disease, diabetes, atrial fibrillation, transient ischemic attack [TIA], or stroke) and later underwent brain autopsy. Given our aim to examine mild cerebrovascular changes (CVCs), individuals were excluded if autopsy revealed large stroke. The most common forms of CVC were circle of Willis atherosclerosis followed by arteriosclerosis, lacunes, and microinfarcts. Excluding the history of TIA/clinical stroke, individual vascular risk factors were not associated with CVC. However, the presence of multiple vascular risk factors was associated with CVC. Furthermore, the presence of CVC was associated with lower Braak and Braak stage. These findings highlight the importance of aggregate risk in the vascular contribution to dementia. Interventions designed to maintain cerebrovascular health may represent important opportunities for preventing or delaying dementia, even when AD is the dominant pathology.

Keywords: Alzheimer's disease; Cerebrovascular disease; Dementia; Neuropathology; Vascular risk.

Figure 1. Aggregate vascular risk burden for Alzheimer’s disease groups with cerebrovascular changes (AD+CVC) and without cerebrovascular changes (AD−CVC)

Bar graph showing the percent of participants in the AD-CVC and AD+CVC groups classified into each of six categories: (1) no elevated risk factor levels (0% of participants fit this category), (2) ≥1 mildly elevated risk factor, (3) ≥1 moderately-to-severely elevated risk factor(s), (4) 1 major risk factor only, (5) ≥2 major risk factors, and (6) ≥3 major risk factors. * χ² = 5.14 (p = .02) for comparison between AD-CVC and AD+CVC

Figure 2. Sum of vascular risk factors for Alzheimer’s disease groups with cerebrovascular changes (AD+CVC) and without cerebrovascular changes (AD−CVC)

A. Bar graph showing the percent of participants in the AD-CVC and AD+CVC groups classified based on the presence of: (1) one or more vascular risk factors, (2) two or more vascular risk factors, and (3) three or more vascular risk factors. Note that these analyses did not involve independent groups (e.g., the “one or more risk factor(s)” category includes participants from the “two or more risk factors” category.) *p < .05 for comparison between AD-CVC and AD+CVC B. Stacked bar chart showing the percent of participants in the AD-CVC and AD+CVC groups with zero, one, two, or three or more vascular risk factors.

Figure 3. Braak and Braak stage for Alzheimer’s disease groups with cerebrovascular changes (AD+CVC) and without cerebrovascular changes (AD−CVC)

A. Proportion of participants in the AD+CVC and AD-CVC groups with lower versus higher severity of neurofibrillary tangle pathology as determined by Braak and Braak stage. Braak and Braak stages were divided into Low (stages IV and V) and High (stage VI). χ² = 6.19 (p = .01) for comparison between AD-CVC and AD+CVC groups on low versus high Braak and Braak stages. B. Proportion of participants in the AD+CVC and AD-CVC groups as a function of Braak and Braak stage (IV, V, or VI). χ² = 6.99 (p = .03) for comparison between AD-CVC and AD+CVC groups on Braak and Braak stages (IV, V, or VI).