Frailty in Parkinson's disease: time to integrate it into treatment decision-making?

Frailty is increasingly defined as a multidimensional clinical condition whose prevalence rises with advancing age, extending across multiple medical specialties and exhibiting significant sex- and gender-related differences. Chronic diseases, including neurological conditions such as Parkinson's disease (PD), are key contributors to frailty, possibly through shared mechanisms. Conversely, frailty adversely influences clinical outcomes and disease trajectories, increases mortality risk and alters the risk-benefit profile of therapeutic interventions. This review summarizes current evidence on the aetiologies, clinical and instrumental assessment, emerging fluid biomarkers, and therapeutic implications of frailty in PD. Conventional frailty tools, including the Frailty Index and Fried phenotype, are useful but lack specificity in this specific population, notably because PD-related symptoms overlap with frailty criteria. A multimodal approach integrating gait and balance analysis, cognitive testing, dysautonomia assessment, sarcopenia screening, dysphagia evaluation, and nutritional markers may improve risk stratification. Emerging biomarkers, including inflammatory cytokines, albumin, C-reactive protein/albumin ratio, vitamin D, sarcopenia-related markers, neurofilament light chain, and glial fibrillary acidic protein (GFAP), may further capture biological vulnerability, although validation remains limited. Frailty substantially modulates PD treatment decisions by increasing susceptibility to adverse effects, polypharmacy, falls, cognitive complications, and procedural risk. Frailty should therefore be systematically integrated into pharmacological prescribing, deprescribing, rehabilitation, neuropalliative approaches, and selection (as well as timing) of device-aided therapies. Routine frailty assessment, independent of chronological age, may support more individualized, patient-centred PD care, prioritizing functional independence, safety, quality of life, and minimisation of treatment burden alongside conventional motor management.