Twenty-six-year change in total cholesterol levels and incident dementia: The Honolulu-Asia aging study

Background: The relationship between total cholesterol levels and dementia is unclear. Objective: To compare the natural history of change in total cholesterol across 26 years between men who did and did not develop dementia 3 years after the last measurement. Design, Setting, and Participants: In the Honolulu-Asia Aging Study, 1027 Japanese American men had total cholesterol levels assayed on 5 occasions between 1965 and 1993 and were screened for dementia on 2 occasions between 1991 and 1996. Main Outcome Measure: The slope of 26-year change in serum total cholesterol levels was estimated by a repeated-measures analysis and was compared between men with incident dementia (n=56) and those without dementia (n=971) at the end of the follow-up period. Results: Cholesterol levels in men with dementia and, in particular, those with Alzheimer disease had declined at least 15 years before the diagnosis and remained lower than cholesterol levels in men without dementia throughout that period. The difference in slopes was robust to adjustment for potential confounding factors, including vascular risk factors, weight change, alcohol intake, and use of lipid-lowering agents. Conclusion: A decline in serum total cholesterol levels may be associated with early stages in the development of dementia.