Early inflammation and dementia: A 25‐year follow‐up of the Honolulu‐Asia aging study

TLDR

Inflammatory responses are linked to cardiovascular disease and may also be associated with dementia. The study examined the long‑term prospective association between dementia and high‑sensitivity C‑reactive protein. A 25‑year follow‑up of Japanese American men measured hs‑CRP at baseline and assessed dementia after 25 years using clinical, neuroimaging, and neuropsychological evaluations. Men in the upper three quartiles of hs‑CRP had a three‑fold higher risk of all dementias, including Alzheimer’s and vascular dementia, with risk increasing by quartile, and these associations were independent of cardiovascular risk factors, suggesting inflammatory markers reflect cerebral disease mechanisms long before symptoms appear.

Abstract

Abstract Inflammatory responses are associated with cardiovascular disease and may be associated with dementing disease. We evaluated the long‐term prospective association between dementia and high‐sensitivity C‐reactive protein, a nonspecific marker of inflammation. Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program (1968–1970) and subsequently were reexamined 25 years later for dementia in the Honolulu‐Asia Aging Study (1991–1996). In a random subsample of 1,050 Honolulu‐Asia Aging Study cases and noncases, high‐sensitivity C‐reactive protein concentrations were measured from serum taken at the second examination; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria. Compared with men in the lowest quartile (<0.34mg/L) of high‐sensitivity C‐reactive protein, men in the upper three quartiles had a 3‐fold significantly increased risk for all dementias combined, Alzheimer's disease, and vascular dementia. For vascular dementia, the risk increased with increasing quartile. These relations were independent of cardiovascular risk factors and disease. These data support the view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear.