Spatio-temporal gait signatures across prodromal and early Parkinson's disease in two independent cohorts.

Gait abnormalities are key features of Parkinson's disease (PD) and might be present in isolated REM Sleep Behavior Disorder (iRBD), a prodromal marker of alpha-synucleinopathy. To assess spatio-temporal gait parameters from prodromal (iRBD) to early/moderate PD stages in normal, fast and dual-task conditions. This prospective multicenter study included two independent cohorts with Polysomnography-confirmed iRBD, drug-naïve PD (naïve-PD), early and moderate treated PD (early-PD, mid-PD), and age-matched healthy controls (HC). Gait was assessed using mobile health technology. A total of 324 participants were enrolled: 194 in the Digital Neurological Assessment (DNA) cohort (23 iRBD, 57 naïve-PD, 49 mid-PD, 65 HC) and 130 in the TPA cohort (28 iRBD, 34 early-PD, 68 HC) composed from TREND, PASS-PD and ABCPD cohorts. In the two independent cohorts, iRBD and early PD (treated and non-treated) showed higher step time compared to HC, especially during dual-task gait. In fast walking, all patient groups had longer step time than HC. Step length was control-like in iRBD and early treated PD, whereas it was lower in both naïve and moderate stages PD in all different task conditions. Temporal gait parameters, especially during dual task walking, are sensitive markers of prodromal PD whereas reduced step length is occurring only in phases when PD diagnosis is already possible. These cross-sectional data need a further validation on ongoing longitudinal studies in prodromal and early stages PD.