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. 2010 Aug;68(2):231-40.
doi: 10.1002/ana.22055.

Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of Aging cohort

Hillary Dolan  1 , Barbara Crain, Juan Troncoso, Susan M Resnick, Alan B Zonderman, Richard J Obrien
Affiliations

Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of Aging cohort

Hillary Dolan et al. Ann Neurol. 2010 Aug.

Abstract

Objective: Although it is now accepted that asymptomatic cerebral infarcts are an important cause of dementia in the elderly, the relationship between atherosclerosis per se and dementia is controversial. Specifically, it is unclear whether atherosclerosis can cause the neuritic plaques and neurofibrillary tangles that define Alzheimer neuropathology and whether atherosclerosis, a potentially reversible risk factor, can influence cognition independent of brain infarcts.

Methods: We examined the relationship between systemic atherosclerosis, Alzheimer type pathology, and dementia in autopsies from 200 participants in the Baltimore Longitudinal Study of Aging, a prospective study of the effect of aging on cognition, 175 of whom had complete body autopsies.

Results: Using a quantitative analysis of atherosclerosis in the aorta, heart, and intracranial vessels, we found no relationship between the degree of atherosclerosis in any of these systems and the degree of Alzheimer type brain pathology. However, we found that the presence of intracranial but not coronary or aortic atherosclerosis significantly increased the odds of dementia, independent of cerebral infarction. Given the large number of individuals with intracranial atherosclerosis in this cohort (136/200), the population attributable risk of dementia related to intracranial atherosclerosis (independent of infarction) is substantial and potentially reversible.

Interpretation: Atherosclerosis of the intracranial arteries is an independent and important risk factor for dementia, suggesting potentially reversible pathways unrelated to Alzheimer pathology and stroke through which vascular changes may influence dementia risk.

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Figures

Figure 1
Figure 1. Relationship between regional atherosclerosis and regional vascular endpoints
Intracranial, cardiac and aortic atherosclerosis grades are plotted +/− S.E. against the rate of any coincident cerebral infarct, myocardial infarct or aortic aneurysm being present (respectively) in the same autopsy specimen. All relationships are significant at the 0.01 level using logistic regression. The odds ratio indicates the increase in odds of the indicated outcome with a step increase in the regional atherosclerosis grade, adjusting for age and sex. Relationships with intracranial atherosclerosis are based on 200 autopsies while aortic and cardiac atherosclerosis are based on 175.
Figure 2
Figure 2. The relationship between atherosclerosis and AD pathology
Multiple indicators of cerebral AD pathology are plotted against the degree of intracranial, cardiac, aortic (graded on a 3 point scale) and composite atherosclerosis (graded on a 4 point scale) +/− S.E. None of the relationships are significant. Associations with intracranial atherosclerosis include data from 200 autopsies and associations with aortic and cardiac atherosclerosis include 175.
Figure 3
Figure 3. The relationship between atherosclerosis and dementia
Intracranial, cardiac and aortic atherosclerosis grades are plotted +/− S.E. against the dementia rate for subjects with those grades. The odds ratio refers to the increase in odds of dementia for a step increase in the regional atherosclerosis grade, adjusting for age and sex. Associations with intracranial atherosclerosis include data from 200 autopsies while associations with aortic and cardiac atherosclerosis include 175.
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