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. 2023 Aug 2;78(8):1417-1426.
doi: 10.1093/gerona/glac213.

Investigating Biological Pathways Underpinning the Longitudinal Association Between Loneliness and Cognitive Impairment

Kexin Yu  1   2   3 , Ted Kheng Siang Ng  4   5   6
Affiliations

Investigating Biological Pathways Underpinning the Longitudinal Association Between Loneliness and Cognitive Impairment

Kexin Yu et al. J Gerontol A Biol Sci Med Sci. .

Abstract

Background: Loneliness precedes the onset of cognitive impairment (CI) in older adults. Although the mechanisms through which loneliness "gets under the skin" to influence the risk of developing CI have been conceptually proposed, they are rarely empirically examined. The Evolutionary Theory of Loneliness posits that loneliness as a stressor could cause dysregulations in multiple physiological systems. The current study investigated whether inflammatory, cardiovascular, and kidney biomarkers mediate the longitudinal association between loneliness and CI.

Methods: Cross-lagged panel models were used to examine the hypothesized relationships, using 2006, 2010, and 2014 waves of data from the Health and Retirement Study (N = 7,037). Loneliness was measured with the 3-item UCLA loneliness scale. CI was assessed with the modified telephone interview for cognitive status. Biomarkers included HbA1C, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, and Cystatin C. Using a stepwise model-building approach, first, the model included only loneliness, CI, and biomarker variables; then, sociodemographic covariates were added; lastly, health status were controlled for.

Results: In unadjusted and partially adjusted models, loneliness was associated with higher odds of worse cognitive status in an 8-year follow-up. Only HbA1C mediated the longitudinal association between loneliness and CI. However, after further controlling for health status, all associations became nonsignificant.

Conclusions: Examining a large number of participants and linking a limited number of biological markers with cognition and loneliness longitudinally, our empirical data did not support theoretical propositions, highlighting the critical importance of controlling for confounders in future studies examining longitudinal mediational relationships underlying loneliness and CI.

Keywords: Biomarkers; Cognitive aging; Epidemiology; Loneliness; Psychosocial.

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Conflict of interest statement

None declared.

Figures

Figure 1.
Figure 1.
Hypothesized biopsychosocial framework of mediating mechanisms on how loneliness “gets under the skin” to increase the odds of cognitive impairment onset via physiological dysregulations.
Figure 2.
Figure 2.
Analytical model for the main analysis. The alphabetic names of the paths correspond to the paths in Table 2.
Figure 3.
Figure 3.
Analytical model for the exploratory analysis. The alphabetic names of the paths correspond to the paths in Supplementary Table 2.
See this image and copyright information in PMC

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