Multidimensional Factors and Predictors of Vulnerability and Frailty in Older Adults: A Systematic Review

Background: Population ageing is characterized by rising multimorbidity and multifaceted vulnerability. While vulnerability is inherently a biopsychosocial state, clinical research predominantly operationalizes risk through physical frailty phenotypes, constraining holistic geriatric care. Identifying the interplay across biological, functional, and psychosocial domains is essential for comprehensive risk evaluation. Objectives: To synthesize multidimensional factors associated with vulnerability and frailty in adults aged ≥65, categorizing cross-sectional correlates and prospective longitudinal predictors to inform multidimensional assessment. Methods: Following PRISMA 2020 guidelines, systematic searches were conducted across PubMed, CINAHL, Scopus, Web of Science, and Google Scholar (2020–2025). Independent reviewers performed screening, selection, extraction, and Joanna Briggs Institute (JBI) critical appraisal (PROSPERO: CRD420251039796). Results: Forty studies (22 cross-sectional, 17 cohort, 1 quasi-experimental) comprising 77,229 cumulative participant observations across community, outpatient, inpatient, and residential care settings were synthesized. Thirty-seven candidate determinants were mapped across five domains: biological/clinical, psychological, socioeconomic/relational, lifestyle, and self-care profile. Advanced age, multimorbidity, and polypharmacy were the most frequent clinical factors; prospective cohorts specifically linked high anticholinergic burden and functional dependence in complex activities to incident frailty. Depressive symptoms, cognitive decline, low education, financial strain, and social isolation consistently delineated vulnerable states. Conclusions: Vulnerability in older adults is a multifaceted construct requiring assessment tools that extend beyond isolated physical markers. Rather than a definitive feature set, these identified factors provide an evidence-based pool of candidate variables that may inform future risk-stratification and predictive modeling initiatives, supporting integrated, person-centered care.