000145159 001__ 145159 000145159 005__ 20250923084437.0 000145159 0247_ $$2doi$$a10.1016/j.lanwpc.2024.101198 000145159 0248_ $$2sideral$$a139961 000145159 037__ $$aART-2024-139961 000145159 041__ $$aeng 000145159 100__ $$aZhao, Xuhao 000145159 245__ $$aIndependent and joint associations of cardiometabolic multimorbidity and depression on cognitive function: findings from multi-regional cohorts and generalisation from community to clinic 000145159 260__ $$c2024 000145159 5060_ $$aAccess copy available to the general public$$fUnrestricted 000145159 5203_ $$aBackground Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings in additional settings, including clinical. Methods Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed for generalization. Participants were eligible for inclusion if they had data for CMM and were free of dementia at baseline. Baseline CMM was defined as: 1) CMM 5, ≥2 among hypertension, hyperlipidemia, diabetes, stroke, and heart disease and 2) CMM 3 (aligned with previous studies), ≥2 among diabetes, stroke, and heart disease. Baseline depression was primarily characterized by binary classification of depressive symptom measurements, employing the Geriatric Depression Scale and the Center for Epidemiological Studies-Depression scale. Global cognition was standardized as z-scores through harmonizing multiple cognitive measures. Longitudinal cognition was calculated as changes in global cognitive z-scores. A pooled individual participant data (IPD) analysis was utilized to estimate the independent and joint associations of CMM and depression on cognitive outcomes in COSMIC studies, both cross-sectionally and longitudinally. Repeated analyses were performed in three external validation studies. Findings Of the 32,931 older adults in the 14 COSMIC cohorts, we included 30,382 participants with complete data on baseline CMM, depression, and cognitive assessments for cross-sectional analyses. Among them, 22,599 who had at least 1 follow-up cognitive assessment were included in the longitudinal analyses. The three external studies for validation had 1964 participants from 3 multi-ethnic Asian older adult cohorts in different settings (community-based, memory clinic, and post-stroke study). In COSMIC studies, each of CMM and depression was independently associated with cross-sectional and longitudinal cognitive function, without significant interactions between them (Ps > 0.05). Participants with both CMM and depression had lower cross-sectional cognitive performance (e.g. β = −0.207, 95% CI = (−0.255, −0.159) for CMM5 (+)/depression (+)) and a faster rate of cognitive decline (e.g. β = −0.040, 95% CI = (−0.047, −0.034) for CMM5 (+)/depression (+)), compared with those without either condition. These associations remained consistent after additional adjustment for APOE genotype and were robust in two-step random-effects IPD analyses. The findings regarding the joint association of CMM and depression on cognitive function were reproduced in the three external validation studies. Interpretation Our findings highlighted the importance of investigating age-related co-morbidities in a multi-dimensional perspective. Targeting both cardiometabolic and psychological conditions to prevent cognitive decline could enhance effectiveness. 000145159 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/B15-17R$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/G03-128R$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/01-0255$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/03-0815$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/06-0617$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/12-02254$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/16-00896$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/19-01874$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/94-1562$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/97-1321E$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/FIS/98-0103 000145159 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000145159 590__ $$a8.1$$b2024 000145159 592__ $$a2.534$$b2024 000145159 591__ $$aHEALTH CARE SCIENCES & SERVICES$$b5 / 185 = 0.027$$c2024$$dQ1$$eT1 000145159 593__ $$aGeriatrics and Gerontology$$c2024$$dQ1 000145159 591__ $$aPUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH$$b15 / 419 = 0.036$$c2024$$dQ1$$eT1 000145159 593__ $$aHealth Policy$$c2024$$dQ1 000145159 591__ $$aPUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH$$b15 / 419 = 0.036$$c2024$$dQ1$$eT1 000145159 593__ $$aInfectious Diseases$$c2024$$dQ1 000145159 593__ $$aPublic Health, Environmental and Occupational Health$$c2024$$dQ1 000145159 593__ $$aObstetrics and Gynecology$$c2024$$dQ1 000145159 593__ $$aPediatrics, Perinatology and Child Health$$c2024$$dQ1 000145159 593__ $$aPsychiatry and Mental Health$$c2024$$dQ1 000145159 593__ $$aInternal Medicine$$c2024$$dQ1 000145159 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000145159 700__ $$aXu, Xiaolin 000145159 700__ $$aYan, Yifan 000145159 700__ $$aLipnicki, Darren M. 000145159 700__ $$aPang, Ting 000145159 700__ $$aCrawford, John D. 000145159 700__ $$aChen, Christopher 000145159 700__ $$aCheng, Ching-Yu 000145159 700__ $$aVenketasubramanian, Narayanaswamy 000145159 700__ $$aChong, Eddie 000145159 700__ $$aBlay, Sergio Luis 000145159 700__ $$aLima-Costa, Maria Fernanda 000145159 700__ $$aCastro-Costa, Erico 000145159 700__ $$aLipton, Richard B. 000145159 700__ $$aKatz, Mindy J. 000145159 700__ $$aRitchie, Karen 000145159 700__ $$aScarmeas, Nikolaos 000145159 700__ $$aYannakoulia, Mary 000145159 700__ $$aKosmidis, Mary H. 000145159 700__ $$aGureje, Oye 000145159 700__ $$aOjagbemi, Akin 000145159 700__ $$aBello, Toyin 000145159 700__ $$aHendrie, Hugh C. 000145159 700__ $$aGao, Sujuan 000145159 700__ $$aGuerra, Ricardo Oliveira 000145159 700__ $$aAuais, Mohammad 000145159 700__ $$aGomez, José Fernando 000145159 700__ $$aRolandi, Elena 000145159 700__ $$aDavin, Annalisa 000145159 700__ $$aRossi, Michele 000145159 700__ $$aRiedel-Heller, Steffi G. 000145159 700__ $$aLöbner, Margit 000145159 700__ $$aRoehr, Susanne 000145159 700__ $$aGanguli, Mary 000145159 700__ $$aJacobsen, Erin P. 000145159 700__ $$aChang, Chung-Chou H. 000145159 700__ $$aAiello, Allison E. 000145159 700__ $$aHo, Roger 000145159 700__ $$aSanchez-Juan, Pascual 000145159 700__ $$aValentí-Soler, Meritxell 000145159 700__ $$aSer, Teodoro del 000145159 700__ $$0(orcid)0000-0002-9098-655X$$aLobo, Antonio$$uUniversidad de Zaragoza 000145159 700__ $$0(orcid)0000-0003-2284-7862$$aDe-la-Cámara, Concepción$$uUniversidad de Zaragoza 000145159 700__ $$0(orcid)0000-0002-1252-2397$$aLobo, Elena$$uUniversidad de Zaragoza 000145159 700__ $$aSachdev, Perminder S. 000145159 700__ $$aXu, Xin 000145159 7102_ $$11007$$2745$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Psiquiatría 000145159 7102_ $$11011$$2615$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Medic.Prevent.Salud Públ. 000145159 773__ $$g51 (2024), 101198 [16 pp.]$$tThe Lancet Regional Health - Western Pacific$$x2666-6065 000145159 8564_ $$s896285$$uhttps://zaguan.unizar.es/record/145159/files/texto_completo.pdf$$yVersión publicada 000145159 8564_ $$s2372724$$uhttps://zaguan.unizar.es/record/145159/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000145159 909CO $$ooai:zaguan.unizar.es:145159$$particulos$$pdriver 000145159 951__ $$a2025-09-22-14:48:12 000145159 980__ $$aARTICLE