Abstract Body: Introduction
Dementia has a long preclinical phase, with pathological and brain changes emerging decades before clinical symptoms appear. Cardiovascular risk factors throughout life contribute to dementia risk, but their effects vary based on their timing and duration. Identifying critical periods of influence is key for developing targeted prevention strategies.
Hypothesis
We hypothesize the association between cardiovascular risk factors and dementia varies across the lifespan.
Methods
We pooled data for 39,524 individuals from seven cohort studies (Whitehall II, ARIC, CHS, HAAS, MESA, SALSA, and FHS) as part of the Dementia Risk Prediction Pooling Project. We imputed trajectories of body mass index (BMI), systolic blood pressure (SBP), fasting glucose, and cholesterol for each participant starting from age 40 years. Time-weighted average exposures during midlife (ages 40-64 years) and later life (ages 65+ years) were calculated, and hazard ratios for dementia incidence were estimated using Cox proportional hazards models. These models accounted for competing risks of death and were adjusted for sex, race, cohort, educational level, and depressive symptoms.
Results
Over a median follow-up of 14 years, there were 5,654 dementia cases and 10,819 deaths. Joint modeling of midlife and late-life risk factors revealed higher BMI, fasting glucose, and cholesterol in midlife were each independently associated with elevated risk of dementia. In contrast, higher late-life values for these factors were associated with lower risk of dementia (Figure). For example, compared to BMI < 20, a BMI ≥ 30 in midlife was associated with a 70% higher risk of dementia, while in late life, it was associated with a 50% lower risk. No association was found between late-life SBP and dementia, but higher midlife SBP was linked to higher risk of dementia. Using rank-based cut offs for risk factors instead of clinical ones did not change the findings.
Conclusion
Midlife, but not later-life, levels of cardiovascular risk factors have a stronger effect on dementia risk, highlighting a critical period for intervention.