Design and protocol of the multimorbidity and mental health cohort study in frailty and aging (MiMiCS-FRAIL): unraveling the clinical and molecular associations between frailty, somatic disease burden and late life depression.

Background: To explore the mutual relationship between multimorbidity, mental illness and frailty, we have set-up the Multimorbidity and Mental health Cohort Study in FRAILty and Aging (MiMiCS-FRAIL) cohort. At the population level, multimorbidity, frailty and late-life depression are associated with similar adverse outcomes (i.e. falls, disability, hospitalization, death), share the same risk factors, and partly overlap in their clinical presentation. Moreover, these three variables may share a common underlying pathophysiological mechanism like immune-metabolic dysregulation. The overall objectives of MiMiCS-FRAIL are 1) to explore (determinants of) the cross-sectional and longitudinal relationship between multimorbidity, depression, and frailty among non-demented geriatric outpatients; 2) to evaluate molecular levels of senoinflammation as a broad pathophysiological process underlying these conditions; and 3) to examine adverse outcomes of multimorbidity, frailty and depression and their interconnectedness.

Methods: MiMiCS-FRAIL is an ongoing observational cohort study of geriatric outpatients in Brazil, with an extensive baseline assessment and yearly follow-up assessments. Each assessment includes a comprehensive geriatric assessment to identify multimorbidity and geriatric syndromes, a structured psychiatric diagnostic interview and administration of the PHQ-9 to measure depression, and several frailty measures (FRAIL, Physical Phenotype criteria, 36-item Frailty Index). Fasten blood samples are collected at baseline to assess circulating inflammatory and anti-inflammatory cytokines, leukocytes' subpopulations, and to perform immune-metabolic-paired miRome analyses. The primary outcome is death and secondary outcomes are the number of falls, hospital admissions, functional ability, well-being, and dementia. Assuming a 5-year mortality rate between 25 and 40% and a hazard rate varying between 1.6 and 2.3 for the primary determinants require a sample size between 136 and 711 patients to detect a statistically significant effect with a power of 80% (beta = 0.2), an alpha of 5% (0.05), and an R between the predictor (death) and all covariates of 0.20. Local ethical board approved this study.

Discussion: Frailty might be hypothesized as a final common pathway by which many clinical conditions like depression and chronic diseases (multimorbidity) culminate in many adverse effects. The MiMiCS-FRAIL cohort will help us to understand the interrelationship between these variables, from a clinical perspective as well as their underlying molecular signature.