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 (BLSA), 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's 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's pathology and stroke through which vascular changes may influence dementia risk.
