Abstract
BACKGROUND: Maintaining independence in older age is an important aspect of quality of life. We investigated depressive symptoms as an important modifiable risk factor that may mediate the effects of physical and cognitive decline on disability. METHODS: We prospectively analyzed data from 223 adults (age 50-85; 117 controls and 106 with type-2 diabetes) over 48 weeks who were participating in a clinical trial "Memory Advancement by Intranasal Insulin in Type 2 Diabetes." Data from self-reported disability (World Health Organization Disability Assessment Schedule) and depressive symptoms (Geriatric Depression Scale) were obtained from baseline, week 25, and week 48 visits. Cognition (Mini-mental status examination) and medical comorbidities (Charlson Comorbidity Index) were assessed at baseline. Longitudinal analysis assessed the extent to which change in depressive symptoms predicted worsening disability. Mediation analyses were performed to determine the extent to which depressive symptoms accounted for disability associated with worse cognition, walking speed, and comorbidities. RESULTS: At baseline, depressive symptoms, cognition, and walking speed were within normal limits, but participants had a high 10-year risk of cardiovascular mortality. Depressive symptoms were related to disability at baseline (p<0.001), and longitudinally (p<0.001). Cognition, walking speed, and comorbidities were associated with disability at baseline (p-values = 0.027-0.001). Depressive symptoms had a large mediating effect on disability longitudinally: the indirect effect on disability via depression accounts for 51% of the effect of cognition, 34% of the effect of mobility, and 24% of the effect of comorbidities. CONCLUSIONS: Depressive symptoms substantially exacerbated the effects of worsening cognition, gait speed, and comorbidities on disability. In our sample, most individuals scored within the "normal" range of the Geriatric Depression Scale, suggesting that even subclinical symptoms can lead to disability. Treating subclinical depression, which may be under-recognized in older adults, should be a public health priority to help preserve independence with aging.