Over a median follow-up of 13.7 years, 47,150 participants developed cardiometabolic disease (CMD).
Biologically older participants showed higher risks of progressing from health to CMD, then to post-CMD dementia, and ultimately to death.
Each standard deviation increase in KDM- acceleration was associated with a 34% higher risk of transitioning from baseline to CMD.
acceleration was linked to a 19% increased risk of moving from baseline to CMD.
KDM-BA acceleration was associated with a 12% increased risk of transitioning from CMD to post-CMD dementia.
Both BA accelerations were more strongly linked to the transition from CMD to post-CMD vascular dementia compared to post-CMD Alzheimer's disease.
Simplified
BACKGROUND: The role of (BA) acceleration in longitudinal disease progression from health to cardiometabolic disease (CMD), then to post-CMD dementia (including vascular dementia (VaD) and Alzheimer's disease (AD)), and finally to death remains unclear.
METHODS: Using data from 284,723 UK Biobank participants, two established BA measures ( [KDM-BA] and ) were generated on the basis of baseline clinical biomarkers. Post-CMD dementia was defined as dementia that occurred after the first occurrence of CMD. Multistate analysis was constructed to examine the association between BA accelerations and longitudinal progression of post-CMD dementia. We further explored the role of two BA accelerations in CMD-specific transitions and dementia-specific transitions, respectively.
RESULTS: Over a median follow-up of 13.7 years, 47,150 participants developed CMD, and 999 developed post-CMD dementia. Biologically older participants demonstrated robustly higher risks from healthy to CMD, then to post-CMD dementia, and finally to death. For the transition from baseline to CMD, adjusted HRs (95% CI) were 1.34 (1.32, 1.35) for each SD increase in KDM-BA acceleration and 1.19 (1.18, 1.20) for PhenoAge acceleration. For the transition from CMD to post-CMD dementia, HRs were 1.12 (1.04, 1.20) for KDM-BA acceleration and 1.10 (1.04, 1.17) for PhenoAge acceleration. Both BA accelerations were more strongly associated with the transition from CMD to post-CMD VaD than with the transition to post-CMD AD.
CONCLUSIONS: BA accelerations hold promise for identifying the disease progression of post-CMD dementia in routine clinical practice and slowing down disease progression through the interventions that slow down biological aging.
Key numbers
1.34
Increase in CMD Risk
Adjusted hazard ratio for KDM- acceleration from baseline to CMD.
1.12
Transition to Post-CMD Dementia Risk
Adjusted hazard ratio for KDM- acceleration from CMD to post-CMD dementia.
1.22
Post-CMD VaD Transition Risk
Adjusted hazard ratio for KDM- acceleration from CMD to post-CMD vascular dementia.
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