Abstract
INTRODUCTION: Genetic variation in the clusterin gene has been associated with Alzheimer Disease (AD), and the clusterin protein is thought to play a mechanistic role. We explored the associations of clusterin plasma levels with incident dementia, AD, and stroke. METHODS: Plasma clusterin was assessed in 1532 nondemented participants from the Framingham Study Offspring cohort between 1998 and 2001 (mean age, 69 ± 6; 53% women). We related clusterin levels to risk of incident dementia, AD, and stroke using Cox-proportional hazards models and examined potential interactions. RESULTS: A significant interaction of plasma clusterin levels with age was observed. Clusterin was significantly associated with increased risk of dementia among elderly persons (>80 years; hazard ratio [HR], 95% confidence interval = 6.25, 1.64-23.89; P = .007) and with decreased risk of dementia (HR = 0.53, 0.32-0.88; P = .013) and stroke (HR = 0.78, 0.63-0.97; P = .029) among younger participants. DISCUSSION: The association between plasma clusterin levels and risk of dementia and stroke may be modified by age or an age-related factor.