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Social health factors (e.g., social activities or social support) and cognitive activity engagement have been associated with dementia risk, but their neural substrates have not been well established. This systematic review and meta-analysis summarizes the available evidence regarding the association between these factors and cerebral macro- and micro-structure. A comprehensive literature search was conducted in various databases, following predefined criteria. Heterogeneity, risk of publication bias and overall certainty of evidence were assessed using standardized scales and, whenever appropriate, random effects meta-analysis was conducted. Of 6715 identified articles, 43 were included. Overall, consistency of findings was low and methodological heterogeneity high for all outcomes. However, in some studies cognitive and social activities were positively associated with total brain, global and cortical grey matter and hippocampal volume as well as white matter microstructural integrity. Furthermore, structural social network characteristics (e.g., social network size) were associated with regional grey matter volumes, while functional social network characteristics (e.g., social support) were additionally associated with total brain volume. Meta-analyses revealed small but significant partial correlations between cognitive and social activities and hippocampal (three studies; n = 892; r z =0.07) and white matter hyperintensity volume (three studies; n = 2934; r z =-0.04). More prospective studies are needed to assess temporal associations., Competing Interests: Declaration of Competing Interest The authors declare to not have any conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)