Palta, Priya

Introduction: Diabetes, a modifiable risk factor for dementia, is thought to impart increased risk of dementia through cerebral small vessel disease. While the importance of diabetes in midlife is well-documented, the influence of different glycemic levels, duration of diabetes, and Alzheimer’s disease genetic risk (apolipoprotein [ APOE ] ε4 genotype) in late-life on dementia risk remains uncertain. This could have implications for individualized prevention strategies. In this study, we investigated whether a higher glycemic level and longer duration of diabetes in late-life is associated with a higher risk of dementia, and whether associations vary by APOE ε4 genotype. Methods: We performed a prospective cohort analysis with the Atherosclerosis Risk in Communities Study using up to 11 years of follow-up (baseline, 2011-2013). We defined diabetes as glycated hemoglobin A1c (HbA 1c ) ≥6.5%, self-reported physician diagnosis, or use of any diabetes medication. Among those with diabetes, we categorized participants as having a lower glycemic level (HbA 1c <7%) or higher level (HbA 1c ≥7%), and duration as short (<5 years) or long (≥5 years). We estimated hazard ratios (HR) for incident dementia by HbA 1c levels and by diabetes duration in separate multivariable-adjusted Cox regression models. We tested for statistical multiplicative interaction on the relative risk of dementia by fitting interaction terms between diabetes measures and APOE ε4 genotype in separate regression models. Results: In 5030 participants without dementia (mean age, 75.4 years; 58.6% female; 21% Black; 28% with diabetes), there were 1167 (23.2%) incident dementia cases over a median follow-up of 9.0 years. Compared to no diabetes, a lower glycemic level and higher level were both associated with elevated dementia risk ( P -trend <.0001; Table). A higher glycemic level was associated with an elevated risk of dementia relative to a lower level (HR=1.47 [95% CI: 1.22-1.77]; Table). Compared to no diabetes, both shorter duration and longer duration were associated with an increase in dementia risk ( P -trend <.0001; Table). Longer duration was associated with an increased risk of dementia relative to shorter duration (HR=1.57 [95% CI: 1.24-1.98]; Table). Associations for glycemic level and diabetes duration did not significantly differ by APOE ε4 genotype (all P >.05). Conclusions: Diabetes management in older adults that includes lower glycemic goals may help reduce dementia risk.

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) is now the predominant HF subtype, largely driven by the syndemic of physical inactivity and overweight/obesity in an aging population. Deranged skeletal muscle energetics and regional ectopic adipose depots are key cardiometabolic pathways in the pathogenesis of HFpEF, both of which may be favorably modified by 1-2 hours/week of resistance exercise (RE). However, its association with HFpEF risk has not been thoroughly examined. We investigated the association between midlife RE behaviors and incident HFpEF in the Atherosclerosis Risk in Communities (ARIC) study. Hypothesis: Participation in RE at midlife is inversely associated with the risk of incident HFpEF. Methods: Our exposure (RE)—including weightlifting and bodyweight resistance exercises—was assessed using the validated Baecke questionnaire and reported weekly RE duration was averaged across Visits 1 and 3 (1987-1995). We dichotomized averaged RE as 0 hr/wk (‘No RE’, reference) and >0 hr/wk (‘Any RE’). Our outcome (incident HFpEF) was identified through committee-adjudicated HF hospitalizations (January 1, 2005 to December 31, 2023) using medical chart abstraction. Participants with prevalent HF, death, or loss to follow-up before January 1, 2005 were excluded. We constructed Cox regression models to evaluate the association between midlife RE and incident HFpEF. Model 1 adjusted for age, sex, race, field center, education, smoking status, alcohol consumption, and non-RE physical activity. Given that adiposity may lie on the causal pathway, waist-height ratio (WHtR; both measured in cm) was added in Model 2. Results: 10,751 Black and White participants (803 incident HFpEF cases) were analyzed over a median follow-up time of 14.4 years (mean±SD Visit 1 age, 53.3±5.6 years; average Visit 1 and 3 WHtR, 0.58±0.08; 24.7% Black; 57.4% female). 1,217 participants (11.3%) reported engaging in RE at Visits 1 and/or 3, with a median duration of 0.84 hr/wk (IQR, 0.50-1.61). Compared to No RE, the fully adjusted hazard ratio (HR) for Model 1 for Any RE was: 0.78 (95% CI, 0.61-1.00, P = 0.05). The association was attenuated after adjustment for WHtR: HR = 0.84 (0.65-1.07, P = 0.16). Conclusion: Participation in RE at midlife is associated with a 22% lower risk of incident HFpEF. To inform public health and clinical guidelines, further studies are needed to clarify the role of RE in HFpEF prevention.