Associations of Social Isolation and Loneliness With Later Dementia

Abstract

ObjectiveTo investigate the independent associations of social isolation and loneliness with incident dementia and to explore the potential neurobiological mechanisms.MethodsWe utilized the UK Biobank cohort to establish Cox proportional hazard models with social isolation and loneliness as separate exposures. Demographic (sex, age and ethnicity), socioeconomic (education level, household income and Townsend deprivation index), biological (BMI, APOE genotype, diabetes, cancer, cardiovascular disease and other disabilities), cognitive (speed of processing and visual memory), behavioral (current smoker, alcohol intake and physical activity), and psychological (social isolation or loneliness, depressive symptoms and neuroticism) factors measured at baseline were adjusted. Then, voxel-wise brain-wide association analyses were used to identify gray matter volumes (GMV) associated with social isolation and with loneliness. Partial least squares regression was performed to test the spatial correlation of GMV differences and gene expression using the Allen Human Brain Atlas.ResultsWe included 462,619 participants (mean age at baseline 57.0 years [SD 8.1]). With a mean follow-up of 11.7 years (SD 1.7), 4,998 developed all-cause dementia. Social isolation was associated with a 1.26-fold increased risk of dementia (95% CI, 1.15-1.37) independently of various risk factors including loneliness and depression (i.e., full adjustment). However, the fully adjusted hazard ratio for dementia related to loneliness was 1.04 (95% CI, 0.94-1.16); and 75% of this relationship was attributable to depressive symptoms. Structural MRI data were obtained from 32,263 participants (mean age 63.5 years [SD 7.5]). Socially isolated individuals had lower GMVs in temporal, frontal and other (e.g., hippocampal) regions. Mediation analysis showed that the identified GMVs partly mediated the association between social isolation at baseline and cognitive function at follow-up. Social isolation-related lower GMVs were related to under-expression of genes that are down-regulated in Alzheimer’s disease and to genes that are involved in mitochondrial dysfunction and oxidative phosphorylation.ConclusionSocial isolation is a risk factor for dementia that is independent of loneliness and many other covariates. Social isolation-related brain structural differences coupled with different molecular functions also support the associations of social isolation with cognition and dementia. Social isolation may thus be an early indicator of an increased risk of dementia.

Physical Fitness, Exercise Behaviors, and Sense of Self-Efficacy Among College Students: A Descriptive Correlational Study

“…The COVID-19 pandemic and the resulting psychological problems pose an unprecedented health crisis and challenge for university students, who are a special group in the context of public health emergencies (Stowe et al, 2020). It has also been shown that people who are socially isolated have poorer cognitive skills, including memory and reaction time, and lower gray matter volume in many parts of the brain (Shen et al, 2022). Self-efficacy, the core concept of Bandura's social cognition theory (Bandura, 1997), refers to the judgments and beliefs that individuals have regarding their ability to organize themselves to perform actions and achieve their goals.…”

The Cognitive Costs of Social Isolation

“…What follows becomes an intellectual challenge to reveal the substructure of social isolation and identify those elements most relevant to dementia risk. Emotional components in light of the Shen et al 3 study seem less important than supposed. The problem might be resolved using psychometric methods to uncover latent factors modulating cognitive impairments seen more often among the socially isolated and show their relevance to dementia risk.…”

“…By itself, this is a useful conclusion, consolidating earlier work, and translates easily into community actions to address health concerns of old people living socially isolated lives. But Shen et al 3 go further and explore this association in ways anticipated by Siebner et al 1 They show that social isolation can be linked to lower than expected GM volumes in brain structures already implicated in the pathogenesis of AD signs and symptoms. Their analytical model was then extended to show underexpression of AD-related genes in participants with identified GM reductions.…”

“…Hitherto, the ill effects of social isolation were explained by the harm caused by the distress of loneliness to critical brain structures. Shen et al 3 improve on this: they distinguish the effects of social isolation from loneliness and show that it is social isolation acting alone and not loneliness that increases the incidence of dementia. By itself, this is a useful conclusion, consolidating earlier work, and translates easily into community actions to address health concerns of old people living socially isolated lives.…”

“…The success of this approach of Shen et al 3 to the complex problem of gene-environment interactions in AD has important implications for research in many neurologic diseases. The goal of some clinical research in neurology is to show how best to use genetically informed brain imaging data to understand the pathogenesis of signs and symptoms in neurologic diseases.…”