Abstract Body: OBJECTIVE: Late-life vascular health and cerebrovascular disease have been identified as potential risk factors for late-life depression (LLD). However, the impact of midlife vascular health, which is strongly linked with other aspects of brain function, on LLD is less understood. This study examined associations of midlife vascular risk factors (VRFs), and the cumulative burden of these factors, with LLD.

METHODS: Individuals from the Atherosclerosis Risk in Communities (ARIC) Study were evaluated for VRFs (smoking, hypertension, diabetes, hypercholesterolemia, and obesity) at midlife (ages 44-66). To assess cumulative vascular risk burden, the number of VRFs were counted and categorized as 0, 1, 2, or ≥3. Approximately 20 years later, LLD was assessed at late-life (ages 66-90) as a Center for Epidemiological Studies Depression Scale (CES-D) score ≥9. The association between VRFs and LLD was examined using logistic regression models adjusted for age, race-center, sex, education, and APOEε4 carrier status. Models were stratified by race; interaction terms were evaluated to assess effect modification.

RESULTS: Among 6,198 participants, the mean age was 52 years, 58.7% were female, and 22.2% were of self-reported Black race. At midlife, 20.2% had 0 VRFs, 41.3% had 1 VRF, 27.2% had 2 VRFs, and 11.3% had 3 or more VRFs. In the overall sample, smoking (OR: 1.68, 95% CI: 1.32-2.12), diabetes (1.41, 95% CI: 1.00-1.98), hypertension (OR: 1.29, 95% CI: 1.02-1.61), and obesity (OR: 1.51, 95% CI: 0.79-1.20) were associated with LLD when combined in one model; hypercholesterolemia was not. Compared to individuals with 0 VRFs in midlife, individuals with 2 VRFs had greater odds of LLD (OR: 1.69, 95% CI: 1.21-2.38), and individuals with 3 or more VRFs had even greater odds of LLD (OR: 2.34, 95% CI: 1.62-3.41). There was effect modification by race: midlife diabetes was associated with LLD in White individuals (OR: 2.18, 95% CI: 1.42-3.25) but not Black individuals (OR: 0.69, 95% CI: 0.36-1.25, p-interaction: 0.0005). Further, having 3 or more VRFs was associated with LLD in White individuals (OR: 3.57, 95% CI: 2.31-5.56), but not in Black individuals (OR: 1.46, 95% CI: 0.75-3.03, p-interaction: 0.01).

CONCLUSION: Midlife vascular risk factors, and the cumulative burden of these factors, were associated with late-life depression (LLD), especially among White individuals. Further studies should evaluate mechanisms for these associations.