The long-term prognosis of late-life depression is poor with regard to mortality and course of depression. Chronic diseases, loneliness, and pain may be used as putative targets for optimizing prevention and treatment strategies for relapse and chronicity.

Among late middle-aged adults, there is a substantial net increase of MDD, which is associated with deteriorating physical health. If morbidity and disability continue to increase, a further expansion of MDD rates may be expected. Improving socioeconomic and psychosocial conditions may benefit public health, as these factors were protective against a higher prevalence of both MDD and SUBD.

Background The frailty index (FI) is a well-recognized measurement for risk stratification in older people. Among middle-aged and older people, we examined the prospective association between the FI and mortality as well as its course over time in relation to multimorbidity and specific disease clusters. Methods A frailty index (FI) was constructed based on either 64 (baseline only) or 35 health deficits (baseline and follow-up) among people aged ≥ 40 years who participated in LifeLines, a prospective population-based cohort living in the Northern Netherlands. Among 92,640 participants, multivariable Cox proportional hazard models were fitted to study the hazard ratio (HR) of the FI at baseline, as well as for 10 chronic disease clusters for all-cause mortality over a 10-year follow-up. Among 55,426 participants, linear regression analyses were applied to study the impact of multimorbidity and of specific chronic disease clusters (independent variables) on the change of frailty over a 5-year follow-up, adjusted for demographic and lifestyle characteristics. Results The FI predicted mortality independent of multimorbidity and specific disease clusters, with the highest impact in people with either endocrine, lung, or heart diseases. Adjusted for demographic and lifestyle characteristics, all chronic disease clusters remained independently associated with an accelerated increase of frailty over time. Conclusions Frailty may be seen as a final common pathway for premature death due to chronic diseases. Our results suggest that initiating frailty prevention at middle age, when the first chronic diseases emerge, might be relevant from a public health perspective.