The effects of cardiovascular risk factors on cognitive compromise.

As life expectancy in the United States continues to increase, the projected numbers of elderly people who will develop dementia will grow rapidly. This paper reviews four well-established cardiovascular risk factors (type 2 diabetes, hypertension, cholesterol, and inflammation), for which there is longitudinal epidemiological evidence of increased risk of dementia, Alzheimer's disease, mild cognitive impairment, and cognitive decline. These risk factors are of special interest because of their potential modifiability, which may affect the course of cognitive compromise. Diabetes is the cardiovascular risk factor (CvRF) most consistently associated with cognition. Hypertension in midlife is consistently associated with cognition, but its associations with late-life hypertension are less clear. Total cholesterol is not consistently associated with cognition. Interleukin-6 and C-reactive protein are inflammatory markers relatively consistently associated with cognition. Composites of the CvRFs increase the risk for dementia in a dose-dependent fashion, suggesting a cumulative effect of these factors on neuronal stress. In the relatively few studies that have reported interactions of risk factors, they potentiate each other. The effect of each of these risk factors varies according to apolipoprotein E genotype. It may be that the effect of these risk factors varies according to the presence of the others, and these complex relationships underlie the biological mechanisms of cognitive compromise. This may be crucial for understanding the effects on cognition of drugs and other approaches, such as lifestyle change, for treating these risk factors.