{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:08:56Z","timestamp":1789016936388,"version":"build-2803163510"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 \u22120.43\/+0.43, stricter \u22120.67\/+0.67 and persistent-state definitions. Logistic GEE estimates were pooled using REML with Hartung-Knapp confidence intervals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u202f=\u202f0.0459, 95% CI 0.0243 to 0.0675;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u202f74.3%) and functional worsening (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u202f=\u202f0.0960, 0.0809 to 0.1111;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u202f41.8%). The functional-minus-cognitive contrast was 0.0534 (0.0325 to 0.0742;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u202f51.6%). Among 266,127 intervals beginning in the distribution-defined unimpaired state, each additional baseline CMM condition was associated with any functional transition (OR\u202f=\u202f1.33, 95% CI 1.27 to 1.40;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u202f64.9%) but not with a common any-cognitive transition effect (OR\u202f=\u202f1.01, 0.95 to 1.07;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u202f81.8%). 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\u202f=\u202f1.39, 1.33 to 1.45;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u202f0%), whereas persistent any-cognitive transition did not (OR\u202f=\u202f0.99, 0.89 to 1.10;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u202f77.0%). Fixed reference-wave thresholds, disease-restricted exposures, cohort exclusions, KLoSA ADL-only scoring and inverse-probability weighting preserved the functional contrast.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1920385","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:32:05Z","timestamp":1789014725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiometabolic multimorbidity and cognitive-functional transitions across international ageing cohorts"],"prefix":"10.3389","volume":"14","author":[{"given":"Ming","family":"Li","sequence":"first","affiliation":[{"name":"Department of Geriatrics, The Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]},{"name":"National Demonstration Center for Experimental Basic Medical Science Education, Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref1","volume-title":"World Report on Ageing and Health","year":"2015"},{"key":"ref2","volume-title":"Multimorbidity: A Priority for Global Health Research","year":"2018"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/S0140-6736(12)60240-2","article-title":"Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study","volume":"380","author":"Barnett","year":"2012","journal-title":"Lancet"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the lancet commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the lancet standing commission","volume":"404","author":"Livingston","year":"2024","journal-title":"Lancet"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e265","DOI":"10.1016\/S2666-7568(23)00054-5","article-title":"Cardiometabolic multimorbidity, lifestyle behaviours, and cognitive function: a multicohort study","volume":"4","author":"Jin","year":"2023","journal-title":"Lancet Healthy Longev"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1093\/gerona\/glz147","article-title":"Multimorbidity and cognitive decline over 14\u202fyears in older Americans","volume":"75","author":"Wei","year":"2020","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1093\/gerona\/gly038","article-title":"Physical functioning decline and mortality in older adults with multimorbidity: joint modeling of longitudinal and survival data","volume":"74","author":"Wei","year":"2019","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1111\/joim.13683","article-title":"Multimorbidity patterns and 18-year transitions from normal cognition to dementia and death: a population-based study","volume":"294","author":"Valletta","year":"2023","journal-title":"J Intern Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"afaf036","DOI":"10.1093\/ageing\/afaf036","article-title":"The trajectories of depression and multimorbidity affect the patterns of cognitive decline: a prospective cohort study","volume":"54","author":"Cui","year":"2025","journal-title":"Age Ageing"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41398-022-02268-3","article-title":"Association between multimorbidity status and incident dementia: a prospective cohort study of 245,483 participants","volume":"12","author":"Hu","year":"2022","journal-title":"Transl Psychiatry"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s13098-023-01186-8","article-title":"Association of cardiometabolic multimorbidity and adherence to a healthy lifestyle with incident dementia: a large prospective cohort study","volume":"15","author":"Xiong","year":"2023","journal-title":"Diabetol Metab Syndr"},{"key":"ref13","volume-title":"Integrated Care for Older People: Guidelines on Community-Level Interventions to Manage Declines in Intrinsic Capacity","year":"2017"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1186\/s12916-025-04400-8","article-title":"Cardiometabolic multimorbidity, social activity, and joint trajectories of physical disability, depressive symptom, and cognitive function in mid-to-late life: a multicohort study","volume":"23","author":"Zhang","year":"2025","journal-title":"BMC Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1093\/ije\/dyu067","article-title":"Cohort profile: the health and retirement study (HRS)","volume":"43","author":"Sonnega","year":"2014","journal-title":"Int J Epidemiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1093\/ije\/dys168","article-title":"Cohort profile: the English longitudinal study of ageing","volume":"42","author":"Steptoe","year":"2013","journal-title":"Int J Epidemiol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1093\/ije\/dys203","article-title":"Cohort profile: the China health and retirement longitudinal study (CHARLS)","volume":"43","author":"Zhao","year":"2014","journal-title":"Int J Epidemiol"},{"key":"ref18","article-title":"Harmonized KLoSA, Version E.2 (2006\u20132020)","volume-title":"Gateway to Global Aging Data","author":"Park","year":"2023"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1093\/ije\/dyu263","article-title":"Cohort profile: the Mexican health and aging study (MHAS)","volume":"46","author":"Wong","year":"2017","journal-title":"Int J Epidemiol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1093\/ije\/dyt088","article-title":"Data resource profile: the survey of health, ageing and retirement in Europe (SHARE)","volume":"42","author":"B\u00f6rsch-Supan","year":"2013","journal-title":"Int J Epidemiol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/biomet\/73.1.13","article-title":"Longitudinal data analysis using generalized linear models","volume":"73","author":"Liang","year":"1986","journal-title":"Biometrika"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/j.0006-341X.2001.00126.x","article-title":"A covariance estimator for GEE with improved small-sample properties","volume":"57","author":"Mancl","year":"2001","journal-title":"Biometrics"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1111\/j.0006-341X.2000.00779.x","article-title":"Correcting for noncompliance and dependent censoring in an AIDS clinical trial with inverse probability of censoring weighted log-rank tests","volume":"56","author":"Robins","year":"2000","journal-title":"Biometrics"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"261","DOI":"10.3102\/10769986030003261","article-title":"Bias and efficiency of meta-analytic variance estimators in the random-effects model","volume":"30","author":"Viechtbauer","year":"2005","journal-title":"J Educ Behav Stat"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1002\/sim.791","article-title":"On tests of the overall treatment effect in meta-analysis with normally distributed responses","volume":"20","author":"Hartung","year":"2001","journal-title":"Stat Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"370","author":"von Elm","year":"2007","journal-title":"Lancet"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e1002571","DOI":"10.1371\/journal.pmed.1002571","article-title":"Clinical, socioeconomic, and behavioural factors at age 50\u202fyears and risk of cardiometabolic multimorbidity and mortality: a cohort study","volume":"15","author":"Singh-Manoux","year":"2018","journal-title":"PLoS Med"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s12874-018-0548-0","article-title":"Does pattern mixture modelling reduce bias due to informative attrition compared to fitting a mixed effects model to the available cases or data imputed using multiple imputation?: a simulation study","volume":"18","author":"Welch","year":"2018","journal-title":"BMC Med Res Methodol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/alz.12050","article-title":"Controlling for selective dropout in longitudinal dementia data: application to the SveDem registry","volume":"16","author":"Handels","year":"2020","journal-title":"Alzheimers Dement"}],"container-title":["Frontiers in Public 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