Associations of healthy aging index with dementia: a prospective cohort study of 305,566 individuals

Purpose: To prospectively assess whether Healthy Aging Index (HAI) is associated with the risk of dementia, and to investigate the potential relationship between HAI and genetic susceptibility in the development of Alzheimer's disease (AD). Methods: The study included 305,566 participants from the UK Biobank, with a median follow-up of 14.01 years. HAI components were systolic blood pressure, reaction time, forced vital capacity, serum cystatin c, and serum glucose. Cox proportional hazard regression models assessed the associations between HAI and dementia risk. Results: Adjusted analyses showed that each one-point increase in HAI was associated with a 15% higher risk of all-cause dementia (HR 1.15, 95% CI 1.13-1.17), a 10% higher risk of AD (HR 1.10, 95% CI 1.07-1.13), and a 29% higher risk of VD (HR 1.29, 95% CI 1.24-1.34). Restricted cubic spline (RCS) analyses confirmed these results. Further, the combined effects of HAI and AD genetic risk score (AD-GRS) were assessed. Participants with HAI scores of 7-10 had a higher risk of AD at intermediate (HR 1.68, 95% CI 1.16-2.44) and high AD-GRS levels (HR 2.43, 95% CI 1.66-3.56). Conclusion: Our study indicates that a higher HAI score is associated with an increased risk of dementia. Early intervention to lower HAI scores in early adulthood, such as adopting a healthy lifestyle, can attenuate these associations.