Cardiometabolic multimorbidity and cognitive-functional transitions across international ageing cohorts

Cardiometabolic multimorbidity (CMM) may accompany changes in cognition and everyday function in later life. We reassessed these associations across international ageing cohorts while addressing outcome structure, unequal threshold severity, measurement precision, repeated observations, mortality and non-death attrition.

We harmonised repeated observations from HRS, ELSA, CHARLS, KLoSA, MHAS and SHARE. Within-interval change in a complete four-condition CMM count (hypertension, diabetes, heart disease and stroke) was used in continuous analyses, whereas transition analyses used interval-baseline CMM4. Fixed-reference, non-overlapping cognitive and functional composites were constructed by cohort. Continuous outcomes were paired cognitive and functional worsening, analysed with participant-clustered Gaussian GEE and a CMM-by-domain interaction. Binary outcomes were any cognitive and any functional transition using cohort-wave-specific thresholds targeting 20% occupancy; sensitivity analyses included 15, 25%, historical -0.43/+0.43, stricter -0.67/+0.67 and persistent-state definitions. Logistic GEE estimates were pooled using REML with Hartung-Knapp confidence intervals.

The data included 236,088 people, 172,518 with at least two waves, and 523,570 scheduled-wave or terminal-death intervals. In 361,562 paired intervals across six cohorts, each additional CMM condition accumulated was associated with cognitive worsening (β = 0.0459, 95% CI 0.0243 to 0.0675; I ² = 74.3%) and functional worsening (β = 0.0960, 0.0809 to 0.1111; I ² = 41.8%). The functional-minus-cognitive contrast was 0.0534 (0.0325 to 0.0742; I ² = 51.6%). Among 266,127 intervals beginning in the distribution-defined unimpaired state, each additional baseline CMM condition was associated with any functional transition (OR = 1.33, 95% CI 1.27 to 1.40; I ² = 64.9%) but not with a common any-cognitive transition effect (OR = 1.01, 0.95 to 1.07; I ² = 81.8%). The functional-to-cognitive ratio of odds ratios was 1.32 (1.23 to 1.42). Persistent any-functional transition was associated with CMM (OR = 1.39, 1.33 to 1.45; I ² = 0%), whereas persistent any-cognitive transition did not (OR = 0.99, 0.89 to 1.10; I ² = 77.0%). Fixed reference-wave thresholds, disease-restricted exposures, cohort exclusions, KLoSA ADL-only scoring and inverse-probability weighting preserved the functional contrast.

CMM was associated with worsening in both continuous domains, with a larger functional coefficient, and with more consistent distribution-defined functional than cognitive transitions. Associations were mainly synchronous, although a smaller delayed cognitive association was observed. Binary states are not diagnoses of mild cognitive impairment, dementia or clinical dependence; findings do not establish causality or a validated screening rule.