Social isolation, loneliness and all-cause dementia: a longitudinal and imaging-genetic study in the UK Biobank cohort

Abstract

INTRODUCTION: Current findings of the relative influence of social isolation and loneliness on dementia are contradictory, and the potential neurobiological mechanisms are unclear. METHODS: We utilized the UK Biobank to investigate the relationships of social isolation and loneliness with dementia (n = 462,619). Neuroanatomical correlates were identified in a subset of participants (n = 32,263). The transcriptomic signatures of related brain changes were characterized by gene enrichment analysis. RESULTS: After full adjustment, social isolation but not loneliness was associated with dementia (hazard ratio: 1.28, 95% confidence interval: 1.17-1.39). Isolated individuals had reduced gray matter volumes in temporal, frontal, occipital and subcortical regions (e.g., hippocampus and amygdala). Relevant brain changes were spatially correlated with genes involved in mitochondrial dysfunction and oxidative phosphorylation, and down-regulated Alzheimer's disease-related genes. DISCUSSION: Social isolation is an independent risk factor for dementia, which could be partly explained by related structural changes coupling with altered molecular functions.

Social isolation, loneliness, and motoric cognitive risk syndrome among older adults in China: A longitudinal study

“…The findings are inconsistent with some prior studies that indicated that social isolation was associated with a higher likelihood of cognitive decline or functional disability 10,16 . One cohort study revealed that socially isolated people had reduced gray matter volumes in temporal, frontal, occipital, and subcortical regions, which were involved in memory and learning, and those changes were not confounded by loneliness 45 . Other studies, however, have suggested that the significant association between social isolation and dementia risk may be due to social isolation as an early consequence rather than a cause of dementia 46 .…”

“…10,16 One cohort study revealed that socially isolated people had reduced gray matter volumes in temporal, frontal, occipital, and subcortical regions, which were involved in memory and learning, and those changes were not confounded by loneliness. 45 Other studies, however, have suggested that the significant association between social isolation and dementia risk may be due to social isolation as an early consequence rather than a cause of dementia. 46 Therefore, more research is needed to identify plausible mechanisms by which social isolation might or might not lower the risk of MCR.…”

“…Women with loneliness showed a 1. 45 literature has implied that an increase in loneliness is associated with cognitive and functional decline and even an increased risk for AD. 17,[36][37][38] Loneliness is reported to be associated with differential activation of attentional networks, visual network, and default mode network.…”