Modifying adult life course dementia risk: results from the Framingham Heart Study.

Background: Modifiable risk factors of dementia identified by the 2020 Lancet Commission, including less education, high alcohol intake, smoking, obesity, physical inactivity, social isolation, diabetes, and hypertension, measured at early adult life, midlife, and late‐life were analyzed for their associations with risk of incident dementia. Method: Participants from the Framingham Heart Study Offspring cohort who attended the fourth examination cycle (1987‐1991) and were free of prevalent dementia were included in the study sample (n = 4,015). They were stratified into three age epochs: early adult life (<45 years, n = 1,079); midlife (45‐65 years, n = 2,476); and late‐life (>65 years, n = 460). Information on alcohol intake, smoking, body mass index, physical activity, and social network, as well as diabetes and hypertension status, were ascertained at the fourth examination cycle, while information on education was ascertained from the second examination cycle. Dementia diagnoses, including all‐cause dementia and Alzheimer's disease (AD) dementia, were adjudicated by a multi‐disciplinary consensus committee through 2019. Cox proportional hazards models were used to examine associations between each risk factor and incident all‐cause dementia and Alzheimer's disease (AD) dementia, stratified by age epoch. Result: Over an average of 21 years of follow‐up (early adult life = 24.0 years; midlife = 20.9 years; late‐life = 13.9 years), increased risk of all‐cause dementia was significantly associated with diabetes (HR = 1.62; 95% CI = 1.07‐2.46; p = 0.023) and physical inactivity (HR = 1.57; 95% CI = 1.12‐2.20; p = 0.009) in midlife, and with obesity (HR = 1.76; 95% CI = 1.08‐2.87; p = 0.024) in late‐life. Obesity in late‐life was associated with increased risk of AD dementia (HR = 2.19; 95% CI = 1.27‐3.77; p = 0.005). All other risk factors examined in early adult life, midlife, and late‐life were not significantly associated with risk of all‐cause dementia (Figure 1) or AD dementia (Figure 2). Conclusion: Results suggest that modifiable risk factors individually may have modest to no impact across the adult life course on dementia risk. Additional studies are needed to determine if these risk factors in combination may have a more synergistic effect. [ABSTRACT FROM AUTHOR]