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Cited by 111Health disparities and outcomesDementia and Cognitive Impairment ResearchAging and Gerontology Research

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Structural Brain Correlates of Loneliness among Older Adults

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Düzel, Sandra, Drewelies, Johanna, Gerstorf, Denis, Demuth, Ilja, Steinhagen-Thiessen, Elisabeth, Lindenberger, Ulman, Kühn, Simone·2019·Scientific Reports
DOI 10.1038/s41598-019-49888-2PMC PMC6753249
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Abstract

Ample evidence indicates that loneliness in old age is associated with poor bodily and mental health. However, little is known about structural cerebral correlates of loneliness in healthy older adults. We examined such correlates in a magnetic resonance imaging (MRI) subsample of 319 older adults aged 61 to 82 years drawn from the Berlin Aging Study II. Using voxel-based morphometry (VBM) and structural equation modeling (SEM), latent hierarchical regression analyses were performed to examine associations of (i) loneliness, (ii) a range of covariates, and (iii) loneliness by covariate interactions with latent brain volume estimates of brain structures known to be involved in processing, expressing, and regulating emotions. Results from whole-brain VBM analyses showed that individuals with higher loneliness scores tended to have smaller gray matter volumes in three clusters comprising (i) the left amygdala/anterior hippocampus, (ii) the left posterior parahippocampus and (iii) the left cerebellum. Significant associations and interactions between loneliness and latent factors for the amygdala and the hippocampus were confirmed with a region-of-interest (ROI)-based approach. These findings suggest that individual differences in loneliness among older adults are correlated with individual differences in the volumes of brain regions that are central to cognitive processing and emotional regulation, also after correcting for confounders such as social network size. We discuss possible mechanisms underlying these associations and their implications.

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Figure 1 Left: Brain regions showing a negative association (red clusters) between loneliness and gray matter volume (p < 0.001; corrected for multiple comparisons; cluster extent threshold k > 97). Upper right panel: Correlation between the individual GM volumes in the first cluster and loneliness score. Lower right panel: Correlation between the individual GM volumes in the second cluster and loneliness score (p < 0.05; all scores are residualized for covariates).
Figure 1 Left: Brain regions showing a negative association (red clusters) between loneliness and gray matter volume (p < 0.001; corrected for multiple comparisons; cluster extent threshold k > 97). Upper right panel: Correlation between the individual GM volumes in the first cluster and loneliness score. Lower right panel: Correlation between the individual GM volumes in the second cluster and loneliness score (p < 0.05; all scores are residualized for covariates).CC BY · PubMed Central
Figure 2 A simplified illustration of the CFA of the latent brain factor model. Model fit is good (χ2 56 = 174.3, RMSEA = 0.058 (CI: 0.044–0.073); CFI = 0.979; SRMR = 0.02). Latent brain factors are drawn in circles. Squares represent observed variables. Single-headed arrows represent significant factor loadings, and double-headed arrows represent covariances. Double-headed arrows with both heads pointing on a manifest variable represent the variance of a variable.
Figure 2 A simplified illustration of the CFA of the latent brain factor model. Model fit is good (χ2 56 = 174.3, RMSEA = 0.058 (CI: 0.044–0.073); CFI = 0.979; SRMR = 0.02). Latent brain factors are drawn in circles. Squares represent observed variables. Single-headed arrows represent significant factor loadings, and double-headed arrows represent covariances. Double-headed arrows with both heads pointing on a manifest variable represent the variance of a variable.CC BY · PubMed Central
Figure 3 Depiction of a simplified SEM (χ2 159 = 249.8, RMSEA = 0.047; CFI = 0.965) showing only all significant main effects of loneliness (lone) and number of confidants (social) as well as the interaction of age (lone*age), sex (lone*sex), education (lone*sex), morbidity (lo*orb), depression (lone*dpr) and optimism (lone*op) with loneliness, which are regressed on the intercorrelated latent brain factors (circles, intercorrelations not shown). Squares represent observed variables. Double-headed arrows with both heads pointing on a manifest variable represent the variance of a variable. Loneliness, depressive affect, openness and educations are represented as mean scores (squares). dlPFC = dorso-lateral-prefrontal cortex, mOFC = medio-orbito-prefrontal cortex, ACC = anterior cingulate cortex, AMY = amygdala, HC = hippocampus, I = insula, and NAcc = nucleus accumbens. Regression coefficients represent standardized estimates.
Figure 3 Depiction of a simplified SEM (χ2 159 = 249.8, RMSEA = 0.047; CFI = 0.965) showing only all significant main effects of loneliness (lone) and number of confidants (social) as well as the interaction of age (lone*age), sex (lone*sex), education (lone*sex), morbidity (lo*orb), depression (lone*dpr) and optimism (lone*op) with loneliness, which are regressed on the intercorrelated latent brain factors (circles, intercorrelations not shown). Squares represent observed variables. Double-headed arrows with both heads pointing on a manifest variable represent the variance of a variable. Loneliness, depressive affect, openness and educations are represented as mean scores (squares). dlPFC = dorso-lateral-prefrontal cortex, mOFC = medio-orbito-prefrontal cortex, ACC = anterior cingulate cortex, AMY = amygdala, HC = hippocampus, I = insula, and NAcc = nucleus accumbens. Regression coefficients represent standardized estimates.CC BY · PubMed Central
Figure 4 Exemplary plot of the interaction between loneliness, age, and left amygdala volume. ROI are extracted from CAT12 preprocessed gray matter maps. For illustration, the participants were divided into two age groups by applying a 69.8 split for age and loneliness across the sample (median age = 69.8 years; younger older adults < 69.8 years, older adults = >69.8 years; low loneliness = −1 SD, high loneliness = +1 SD).
Figure 4 Exemplary plot of the interaction between loneliness, age, and left amygdala volume. ROI are extracted from CAT12 preprocessed gray matter maps. For illustration, the participants were divided into two age groups by applying a 69.8 split for age and loneliness across the sample (median age = 69.8 years; younger older adults < 69.8 years, older adults = >69.8 years; low loneliness = −1 SD, high loneliness = +1 SD).CC BY · PubMed Central

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Metadata

Authors
Düzel, S., Drewelies, J., Gerstorf, D., Demuth, I., Steinhagen-Thiessen, E., Lindenberger, U., & Kühn, S.
Affiliations
  • Max Planck Institute for Human Development (DE)
  • Humboldt-Universität zu Berlin (DE)
  • University Medical Center Hamburg-Eppendorf (DE)
Corresponding author
Düzel, Sandra
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-09-19
Volume
9
Issue
1
Pages
13569-13569
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-49888-2
PMC
PMC6753249
OpenAlex
W2974655760
Cited by
111
References
81
Citations by year
2026: 16 · 2025: 22 · 2024: 16 · 2023: 11 · 2022: 21 · 2021: 18 · 2020: 7
FWCI
11.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
Bundesministerium f&#x00FC;r Bildung und Forschung (16SV5537/16SV5837/16SV5538/16SV5536K/01UW0808/01UW0706)
Topics
  • Social Sciences › Health › Health disparities and outcomes
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Social Sciences › Psychology › Developmental and Educational Psychology › Aging and Gerontology Research
Keywords
loneliness, older adults, gray matter volume, amygdala, hippocampus, cerebellum, emotion regulation, brain structure, social network size, aging
MeSH terms
Aged, Aged, 80 and over, Amygdala, Brain Mapping, Female, Hippocampus, Humans, Loneliness, Magnetic Resonance Imaging, Male, Middle Aged, Multivariate Analysis, Gray Matter

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