Cerebrovascular disease, APOE epsilon4 allele and cognitive decline in a cognitively normal population

Abstract

Objectives: To investigate whether cerebrovascular disease (CVD) and apolipoprotein E (APOE) epsilon4 allele were associated with cognitive decline and whether the relationship between CVD and cognitive decline varied by APOE epsilon4 status.

Methods: A total of 809 cognitively normal community-dwelling residents aged >75 years were followed to detect subjects with cognitive decline, defined as follow-up. Mini-mental state examination (MMSE) score was >10% decease of the baseline score. Logistic and multinomial logistic models were developed to estimate odds ratio (OR) and 95% confidence interval (CI) of cognitive decline related to a history of CVD and APOE epsilon4 by taking into account major potential confounders including baseline MMSE score.

Results: During the mean 3.5 years of follow-up, 190 subjects experienced cognitive decline. Multi-adjusted ORs (95% CIs) of overall cognitive decline were 2.27 (1.23-4.17) for CVD and 1.69 (1.13-2.54) for APOE epsilon4, but no interaction was detected. Multinomial logistic analysis led to the CVD-related ORs of 1.42 (0.75-2.67) for cognitive decline without progression to dementia and 3.41 (1.55-7.55) for the decline progressing to dementia; similar analysis from a separate model led to adjusted OR of 2.28 (0.88-5.87; p=0.09) for the decline progressing to Alzheimer's disease. The risk effects of CVD on cognitive decline with progression to dementias were statistically significant mainly among individuals without APOE epsilon4 allele.

Conclusions: CVD is a major risk factor for cognitive decline associated with progression to dementia and Alzheimer's disease. There appears no interaction between CVD and APOE epsilon4 on cognitive decline in very old people.