Physical frailty, depressive symptoms, and cognitive decline before and after Parkinson’s disease diagnosis: a population-based prospective study of the SHARE and ELSA cohorts

Parkinson's disease (PD) is increasingly common, yet its multidomain prodromal evolution remains incompletely characterised. Among 49,039 participants aged ≥50 years from the Survey of Health, Ageing and Retirement in Europe (SHARE), 624 incident PD cases occurred for up to 9 years. Compared with non-frailty, physical frailty was associated with a higher PD risk (HR = 2.31, 95% CI: 1.82-2.94); corresponding HRs were 1.95 (95% CI: 1.55-2.46) for severe depressive symptoms and 1.66 (95% CI: 1.34-2.06) for severe cognitive impairment. Risks were greatest when deficits co-occurred across all three domains (HR = 3.20, 95% CI: 2.42-4.24). Short-term worsening in multidomain health was associated with higher PD risk, whereas recovery to a more favourable state was associated with lower risk. The joint trajectory characterised by high physical frailty, high depressive symptoms, and low cognitive performance showed the highest risk of PD (HR = 4.21, 95% CI: 2.36-7.51). PD was also associated with progression to less favourable health states and reduced recovery, while future PD cases in both the SHARE and English Longitudinal Study of Ageing (ELSA) showed faster pre-diagnostic deterioration, particularly in depressive symptoms and verbal fluency, with abrupt worsening around diagnosis. These findings support repeated multidomain monitoring to improve PD risk stratification in older adults.