The underlying neurobiology of social isolation and loneliness in middle-older adults: A systematic review.
- 1Institute for Physical Activity and Nutrition, Deakin University, Geelong, Victoria, Australia.
- 2Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Victoria, Australia.
Abstract
Social isolation and loneliness are distinct but overlapping dementia risk factors, though their underlying neurobiological mechanisms remain unclear. A systematic search identified 42 studies examining social isolation, loneliness, and neurobiological outcomes in middle-aged and older adults, including structural and functional neuroimaging, neuroinflammatory, and neurodegenerative markers. Findings identified patterns of neurobiological associations that were reported exclusively for social isolation, exclusively for loneliness, and shared across both concepts. Social isolation was more frequently associated with temporal regions (middle temporal gyrus, temporal lobe), whereas loneliness demonstrated associations with subcortical structures (putamen, globus pallidus). Shared patterns of association were most evident in limbic regions (hippocampus, amygdala, thalamus, fusiform gyrus). Both constructs were also associated with greater white matter hyperintensity/lesion volume and elevated C-reactive protein. Several implicated regions are vulnerable in dementia, suggesting potential neurobiological pathways linking poor social health to neurodegenerative risk. However, substantial methodological heterogeneity and inconsistent measurement approaches limit conclusions and highlight important directions for future research.
Related
- Social isolation, self-perceived loneliness, and the 7-year trajectories of depression and cognitive decline: a prospective cohort study
- Relationship Between Social Isolation, Loneliness, and Systemic Inflammation: A Scoping Review of Biological Signatures and Clinical Outcomes.
- Social isolation, loneliness and subsequently developing risk for autoimmune diseases: A prospective study from UK Biobank
- Chronic loneliness and isolation phenotypes and physical and mental health in older adults
- Associations of digital self-efficacy and social network connectedness with loneliness among urban older adults in kerman, iran: a cross-sectional study
BibTeX
@article{guarnera2026underlying,
title = {{The underlying neurobiology of social isolation and loneliness in middle-older adults: A systematic review.}},
author = {Jade Guarnera and Katherine Kenyon and Neel Joshi and Karen Caeyenberghs and Michael Wheeler and Helen Macpherson},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
month = oct,
doi = {10.1002/alz.71921},
url = {https://europepmc.org/article/MED/42948906},
note = {CC BY},
}
RIS
TY - JOUR
TI - The underlying neurobiology of social isolation and loneliness in middle-older adults: A systematic review.
AU - Jade Guarnera
AU - Katherine Kenyon
AU - Neel Joshi
AU - Karen Caeyenberghs
AU - Michael Wheeler
AU - Helen Macpherson
PY - 2026
DA - 2026/10/01
JO - Alzheimer's & dementia : the journal of the Alzheimer's Association
DO - 10.1002/alz.71921
UR - https://europepmc.org/article/MED/42948906
AB - Social isolation and loneliness are distinct but overlapping dementia risk factors, though their underlying neurobiological mechanisms remain unclear. A systematic search identified 42 studies examining social isolation, loneliness, and neurobiological outcomes in middle-aged and older adults, including structural and functional neuroimaging, neuroinflammatory, and neurodegenerative markers. Findings identified patterns of neurobiological associations that were reported exclusively for social isolation, exclusively for loneliness, and shared across both concepts. Social isolation was more frequently associated with temporal regions (middle temporal gyrus, temporal lobe), whereas loneliness demonstrated associations with subcortical structures (putamen, globus pallidus). Shared patterns of association were most evident in limbic regions (hippocampus, amygdala, thalamus, fusiform gyrus). Both constructs were also associated with greater white matter hyperintensity/lesion volume and elevated C-reactive protein. Several implicated regions are vulnerable in dementia, suggesting potential neurobiological pathways linking poor social health to neurodegenerative risk. However, substantial methodological heterogeneity and inconsistent measurement approaches limit conclusions and highlight important directions for future research.
SN - 1552-5260
SN - 1552-5279
ER -