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. 2024 Oct;55(10):2449-2458.
doi: 10.1161/STROKEAHA.124.047455. Epub 2024 Aug 28.

Psychosocial Health and the Association Between Cerebral Small Vessel Disease Markers With Dementia: The ARIC Study

Surabhee Eswaran  1 , David S Knopman  2 , Silvia Koton  3   4 , Anna M Kucharska-Newton  5 , Albert C Liu  5 , Chelsea Liu  6 , Pamela L Lutsey  7 , Thomas H Mosley Jr  8 , Priya Palta  9 , A Richey Sharrett  4 , Kevin J Sullivan  8 , Keenan A Walker  10 , Rebecca F Gottesman  11 , Renee C Groechel  11
Affiliations

Psychosocial Health and the Association Between Cerebral Small Vessel Disease Markers With Dementia: The ARIC Study

Surabhee Eswaran et al. Stroke. 2024 Oct.

Abstract

Background: Associations between magnetic resonance imaging markers of cerebral small vessel disease (CSVD) and dementia risk in older adults have been established, but it remains unclear how lifestyle factors, including psychosocial health, may modify this association.

Methods: Social support and social isolation were assessed among participants of the community-based ARIC (Atherosclerosis Risk in Communities) Study, via self-reported questionnaires (1990-1992). Following categorization of both factors, participants were classified as having strong or poor mid-life social relationships. At visit 5 (2011-2013), participants underwent 3T brain magnetic resonance imaging quantifying CSVD measures: white matter hyperintensity volume, microbleeds (subcortical), infarcts (lacunar), and white matter integrity (diffusion tensor imaging). Incident dementia cases were identified from the time of imaging through December 31, 2020 with ongoing surveillance. Associations between CSVD magnetic resonance imaging markers and incident dementia were evaluated using Cox proportional-hazard regressions adjusted for demographic and additional risk factors (from visit 2). Effect modification by mid-life social relationships was evaluated.

Results: Of the 1977 participants with magnetic resonance imaging, 1617 participants (60.7% women; 26.5% Black participants; mean age at visit 2, 55.4 years) were examined. In this sample, mid-life social relationships significantly modified the association between white matter hyperintensity volume and dementia risk (P interaction=0.001). Greater white matter hyperintensity volume was significantly associated with risk of dementia in all participants, yet, more substantially in those with poor (hazard ratio, 1.84 [95% CI, 1.49-2.27]) versus strong (hazard ratio, 1.26 [95% CI, 1.08-1.47]) mid-life social relationships. Although not statistically significant, subcortical microbleeds in participants with poor mid-life social relationships were associated with a greater risk of dementia, relative to those with strong social relationships, in whom subcortical microbleeds were no longer associated with elevated dementia risk.

Conclusions: The elevated risk of dementia associated with CSVD may be reduced in participants with strong mid-life social relationships. Future studies evaluating psychosocial health through the life course and the mechanisms by which they modify the relationship between CSVD and dementia are needed.

Keywords: atherosclerosis; cognitive reserve; dementia; social isolation; white matter.

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Conflict of interest statement

Dr Knopman serves on a Data Safety Monitoring Board for the Dominantly Inherited Alzheimer Network Treatment Unit study. He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. He has served as a consultant for Roche, Samus Therapeutics, Magellan Health, Biovie, and Alzeca Biosciences but receives no personal compensation. He attended an Eisai advisory board meeting for lecanemab on December 2, 2022 but received no compensation directly or indirectly. He receives funding from the NIH and grants from Washington University School of Medicine in St. Louis. Dr Lutsey reports grants from the National Institutes of Health (NIH) to her institution. Dr Mosley is supported by NIH/National Heart, Lung, and Blood Institute (NHLBI) 75N92022D0004 and NIH/NHLBI: U01HL096812. Dr Palta is supported by NIH/NHLBI 75N92022D00005. Dr Walker is supported by the National Institute on Aging’s Intramural Research Program (AG000348-01, AG000349-01). Dr Gottesman served on the American Neurological Association as program chair from 2021 to 2023 and received no personal compensation. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Study Population Flow
Figure 2.
Figure 2.. Adjusted Hazard Ratios for Associations of MRI Markers with Dementia Risk
*P ≤ 0.05; **P ≤ 0.01; Results reflect Cox proportional-hazards model 2 adjustments. WMH volume divided into tertiles after normalization for intracranial volume, thus overlap exists among tertiles because dataset initially included non-normalized WMH volumes. WMH percentage tertiles: Smallest:0.09–2.39%, Middle:1.53–4.54%, Greatest:3.18–22.33% DTI,indicates diffusion tensor imaging; FA,fractional anisotropy, MD,mean diffusivity; WMH,white matter hyperintensities
Figure 3.
Figure 3.. Adjusted Hazard Ratios for Associations of MRI Markers with Dementia Risk, Stratified by Mid-Life Social Relationships
*P ≤ 0.05; **P ≤ 0.01; Results reflect Cox proportional-hazards model 2 adjustments, stratified by mid-life social relationship (strong vs. poor) ††Effect modification with statistically significant interaction term (p-interaction = 0.001; remained significant after Bonferroni correction) DTI indicates diffusion tensor imaging; FA,fractional anisotropy; MD,mean diffusivity; WMH,white matter hyperintensities
Figure 4.
Figure 4.. Kaplan Meier curves for Dementia-Free Survival by Mid-Life Social Relationships and Indicated MRI Markers
Rates of dementia incidence significantly differed (log-rank p<0.001) in participants with varying levels of social relationships and by each respective marker. SMB indicates subcortical microbleeds; WMH,white matter hyperintensities
See this image and copyright information in PMC

Comment in

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