Associations of accelerated biological ageing with incident dementia, cognitive functions and brain structure: a prospective cohort study based on UK Biobank.

Background: Several small-sample studies have suggested that biological processes of ageing are implicated with dementia and cognitive function. We aimed to prospectively investigate the associations of biological age with incident dementia, cognitive functions and brain structure based on the UK Biobank.

Methods: A total of 287 846 participants without dementia at baseline (followed until November 2022) were analysed. We measured biological age from clinical traits using the Klemera-Doubal method Biological Age (KDM-BA) and PhenoAge algorithms. Cox models were applied to evaluate the risk of dementia. Logistic regression models and linear regression models were used to assess the association between cognitive functions and brain structural measures.

Results: During a median follow-up of 13.68 years, 4744 incident all-cause dementia (ACD) events (including 3013 Alzheimer's disease (AD) and 853 vascular dementia (VaD)) were recorded. Participants with older biological age were at increased risk of incident dementia (HR=1.35, 95% CI 1.23 to 1.48 for KDM-BA acceleration, 1.71 (1.52 to 1.91) for PhenoAge acceleration). Those with the highest level of KDM-BA and PhenoAge acceleration had the highest risk of ACD risk, with the corresponding HR of 1.80 (95% CI 1.60 to 2.03) and 1.19 (1.09 to 1.29), respectively. The associations between biological ageing with AD and VaD were also significant. Furthermore, a higher level of biological age was associated with worse performance in multiple cognitive domains and brain structural measures.

Conclusion: A higher level of biological age may represent a potential risk factor for incident dementia and is associated with worse performance in multiple cognitive domains and brain structural measures.