Multi-morbidity, dependency, and frailty singly or in combination have different impact on health outcomes.

Multi-morbidity, dependency, and frailty were studied simultaneously in a community-living cohort of 4,000 men and women aged 65 years and over to examine the independent and combined effects on four health outcomes (mortality, decline in physical function, depression, and polypharmacy). The influence of socioeconomic status on these relationships is also examined. Mortality data was documented after a mean follow-up period of 9 years, while other health outcomes were documented after 4 years of follow-up. Fifteen percent of the cohort did not have any of these syndromes. Of the remaining participants, nearly one third had multi-morbidity and frailty (pre-frail and frail), while all three syndromes were present in 11 %. All syndromes as well as socioeconomic status were significantly associated with all health outcomes. Mortality was only increased for age, being male, frailty status, and combinations of syndromes that included frailty. Both multi-morbidity and frailtymale was protective. Only a combination of all three syndromes, and age per se, increased the risk of depressive symptoms at 4 years while being male conferred reduced risk. Multi-morbidity, but not frailty status or dependency, and all syndrome combinations that included multi-morbidity were associated with use of ≥ four medications. Decline in homeostatic function with age may thus be quantified and taken into account in prediction of various health outcomes, with a view to prevention, management, formulation of guidelines, service planning, and the conduct of randomized controlled trials of interventions or treatment.