Browsing by Author "Xu, Xiaolin"

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    Additive Impact of Cardiometabolic Multimorbidity and Depression on Cognitive Decline: Findings from Multi‐Regional Cohorts and Generalization from Community to Clinic
    (Wiley, 2025-01-09) Zhao, Xuhao; Yan, Yifan; Lipnicki, Darren M.; Pang, Ting; Chen, Christopher; Wong, Tien Yin; Cheng, Ching Yu; Venketasubramanian, Narayanaswamy; Chong, Eddie; Costa, Erico; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Carriere, Isabelle; Scarmeas, Nikolaos; Gureje, Oye; Hendrie, Hugh C.; Gao, Sujuan; Guerra, Ricardo Oliveira; Rolandi, Elena; Riedel-Heller, Steffi G.; Ganguli, Mary; Aiello, Allison E.; Ho, Roger Chun-Man; Sanchez-Juan, Pascual; Lobo, Antonio; Sachdev, Perminder S.; Xu, Xiaolin; Xu, Xin; Psychiatry, School of Medicine
    Background: To estimate the additive associations of cardiometabolic multimorbidity (CMM) and depression on long‐term cognitive trajectory in multi‐regional cohorts and validate the generalizability of the findings in varying clinical settings. Method: 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 to assess generalizability. Cross‐sectional and longitudinal analyses were conducted. CMM was defined as: 1) CMM5: ≥ 2 among hypertension, hyperlipidemia, diabetes mellitus, stroke, and heart disease and 2) CMM3 (aligned with previous studies): ≥ 2 among diabetes mellitus, stroke, and heart disease. Depression was identified using the Geriatric Depression Scale, Center for Epidemiological Studies‐Depression scale, or medical history. A one‐step individual participant data meta‐analysis was utilized to investigate associations between the co‐occurrence of CMM and depression and cognitive outcomes in the COSMIC studies. Stratified analyses were conducted based on baseline dementia status, demographics, and APOE genotype. Repeated analyses were performed in external validation studies for generalization. Result: Of the 32,450 older adults in the 14 COSMIC cohorts, we included 31,243 participants with complete data on CMM, depression, and cognitive assessment for cross‐sectional analyses. Among them, 23,242 who had at least 1 follow‐up cognitive assessment were included in the longitudinal analyses. From the three external studies we included 1964 participants, representing 3 multi‐ethnic Asian elderly cohorts (community cohort, memory clinic cohort, and stroke cohort). In the COSMIC studies analysis, the co‐occurrence of CMM and depression was associated with both cross‐sectional cognitive performance (β = ‐0.20, 95%CI = (‐0.25,‐0.16) for CMM5 and depression, β = ‐0.17, (95%CI = ‐0.044,‐0.031) for CMM3 and depression), and rate of cognitive decline (β = ‐0.038, 95%CI = (‐0.25,‐0.16) for CMM5 and depression, β = ‐0.023, (95%CI = ‐0.036, ‐0.009) for CMM3 and depression). This combined effect remained consistent across different subgroups particularly among participants without dementia. These findings were reproduced in the three external validation studies. Conclusion: Our study demonstrated an additive effect between CMM and depression on cognitive decline. Targeting both cardiometabolic and psychological conditions could lead to greater effectiveness in delaying or preventing cognitive decline.
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    Independent and joint associations of cardiometabolic multimorbidity and depression on cognitive function: findings from multi-regional cohorts and generalisation from community to clinic
    (Elsevier, 2024-09-12) Zhao, Xuhao; Xu, Xiaolin; Yan, Yifan; Lipnicki, Darren M.; Pang, Ting; Crawford, John D.; Chen, Christopher; Cheng, Ching-Yu; Venketasubramanian, Narayanaswamy; Chong, Eddie; Blay, Sergio Luis; Lima-Costa, Maria Fernanda; Castro-Costa, Erico; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scarmeas, Nikolaos; Yannakoulia, Mary; Kosmidis, Mary H.; Gureje, Oye; Ojagbemi, Akin; Bello, Toyin; Hendrie, Hugh C.; Gao, Sujuan; Guerra, Ricardo Oliveira; Auais, Mohammad; Gomez, José Fernando; Rolandi, Elena; Davin, Annalisa; Rossi, Michele; Riedel-Heller, Steffi G.; Löbner, Margit; Roehr, Susanne; Ganguli, Mary; Jacobsen, Erin P.; Chang, Chung-Chou H.; Aiello, Allison E.; Ho, Roger; Sanchez-Juan, Pascual; Valentí-Soler, Meritxell; Del Ser, Teodoro; Lobo, Antonio; De-la-Cámara, Concepción; Lobo, Elena; Sachdev, Perminder S.; Xu, Xin; Cohort Studies of Memory in an International Consortium (COSMIC); Psychiatry, School of Medicine
    Background: 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.