Biological Age, Not Chronological Age, Is Associated with Late-Life Depression

Abstract

Background: The pathophysiology of late-life depression (LLD) is complex and heterogeneous, with age-related processes implicated in its pathogenesis. This study examined the cross-sectional and longitudinal association between depressive symptoms and a baseline multibiomarker algorithm of biological age (BA) that aggregates indicators of inflammatory, metabolic, cardiovascular, lung, liver, and kidney functioning.

Method: Data were analyzed from 2,776 men and women from the prospective observational Health Aging and Body Composition Study, who had both evaluable chronological age (CA) and BA. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale.

Results: A covariate-adjusted regression model showed that BA (B = 0.03, p = .0471) but not CA (B = -0.01, p = .7185) is associated with baseline CES-D scores. The mean baseline BA for individuals with a CES-D ≥ 10 was 1.28 years greater than in those with a CES-D < 10. Comparatively, there is only a 0.05-year difference in mean CA between the two depression groups. A covariate-adjusted longitudinal model found that baseline BA predicts CES-D score at follow-up (B = 0.04, p = .0058), whereas CA does not (B = 0.03, p = .4125). Additionally, an older BA significantly predicted a CES-D ≥ 10 (B = 0.02, p = .032) over a 10-year period.

Conclusions: A multibiomarker index of an older adult's BA outperformed their CA in predicting subsequent increased and clinically significant depressive symptoms. This result supports the evolving view of LLD as a brain disorder resulting from deleterious age-associated changes across numerous physiological systems.

Figure 1.

The predicted prevalence of significant depressive symptoms and cognitive impairment at baseline as a function of baseline biological and chronological age. (a) Significant depressive symptoms (CES-D ≥ 10). (b) Significant cognitive impairment (3MS ≤ 78). Note: Depicted is the predicted prevalence of experiencing significant depressive symptoms (Figure 1a; CES-D ≥ 10) and significant cognitive impairment (Figure 1b; 3MS ≤ 78) at baseline with the 95% confidence intervals plotted against BA and CA. The regression line for CA was extended beyond the baseline age range (68–80 years; reflected as a dashed line) for ease of comparison between BA and CA. BA = Biological age; CA = Chronological age; CES-D = Center for Epidemiologic Studies Depression scale.