AbstractIntroductionTo investigate the association between cardiometabolic multimorbidity (CMM) patterns and dementia‐related neuropsychiatric symptoms (NPSs) among multiregional and ethnic seniors.MethodsFour Asian studies (discovery) and UK Biobank (validation) were included. CMM was defined as two or more of hypertension, hyperlipidemia, diabetes mellitus, stroke, and heart disease. The latent class analysis identified CMM patterns. Two‐step individual participant data (IPD) and Cox regressions explored associations between CMM and the presence and short‐term (1–2 years) incidence of four neuropsychiatric subsyndromes: psychosis, hyperactivity, affective, and apathy.ResultsA total of 2950 Asian and 40,424 UK participants were included. Metabolic multimorbidity (≥2 of hypertension, hyperlipidemia, and diabetes mellitus) was associated with the presence (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.00–1.81; and 1.93, 1.73–2.16; in the respective data set), and incidence (hazard ratio [HR] = 3.91, 1.53–10.01; and 6.94, 2.52–19.07) of affective subsyndrome. Cardio‐cerebrovascular multimorbidity (≥2 of hypertension, stroke, and heart disease) was not associated with any NPSs.DiscussionMetabolic multimorbidity may exacerbate the neuropsychiatric disturbances of possible dementia.Highlights Four Asian multiregional and ethnic studies were included as the discovery data set, with the UK Biobank being applied as the validation data set. Metabolic multimorbidity had a higher presence and short‐term incidence of affective syndromes. Cardio‐cerebrovascular multimorbidity was not associated with any neuropsychiatric symptoms.