Data-driven discovery of midlife cardiometabolic profile associated with incident early-onset and late-onset dementia

Background

Cardiometabolic risk factors have been associated with the risk of late-onset dementia. However, evidence regarding early-onset dementia was inconsistent, and the impact of clustered cardiometabolic risk factors was unclear. We aimed to investigate the associations of cardiometabolic profiles with incident early-onset and late-onset dementia.

Methods

Among 289 494 UK Biobank participants, cluster analysis was built on 12 common cardiometabolic markers. Analyses were performed on those aged <65 years at baseline (n = 249 870) for early-onset dementia and those ≥65 at the end of follow-up (n = 191 213) for late-onset dementia.

Results

During a median follow-up of 14.1 years, 279 early-onset dementia cases and 3167 late-onset dementia cases were documented. Among the five clusters of cardiometabolic profiles identified (cluster 1 [obesity-dyslipidemia pattern], cluster 2 [high blood pressure pattern], cluster 3 [high liver enzymes pattern], cluster 4 [inflammation pattern] and cluster 5 [relatively healthy pattern]), cluster 3 was significantly associated with higher risks of both early-onset and late-onset dementia; however, the risk estimate for early-onset dementia (hazard ratio 2.58, 95% CI 1.61–4.14) was larger than that for late-onset dementia (1.36, 1.09–1.71). Cluster 4 was associated with a higher risk of late-onset dementia (hazard ratio 1.39, 95% CI 1.13–1.72). No significant interactions were observed between cardiometabolic clusters and apolipoprotein E ε4 genotype.

Conclusions

Cardiometabolic patterns characterised by relatively high liver enzyme levels or systemic inflammation were associated with increased risks of early-onset and late-onset dementia. Identification of high-risk subgroups according to distinct cardiometabolic patterns might help develop more precise strategies for dementia prevention regardless of apolipoprotein E (APOE) ε4 status.