Intra‑individual Variability of Activities of Daily Living as a Marker of Cognitive Status in Parkinson’s Disease: The Role of Subjective Cognitive Decline and CSF Biomarkers

Parkinson’s disease (PD) is characterized by motor and non motor symptoms, including cognitive decline that compromises activities of daily living (ADL). PD patients vary significantly in ADL impairment profiles, with motor versus cognitive dysfunction producing distinct functional consequences. Identifying cognitive-related ADL impairment associated with mild cognitive impairment (MCI) or dementia is clinically important, but traditional aggregate ADL scores obscure this heterogeneity. This cross sectional study in 265 non demented PD patients investigated if intra individual ADL variability (ADL SD) serves as a cognitive status marker, alongside demographic, clinical, cognitive, and CSF biomarkers (α synuclein, amyloid β₁₋₄₂, total tau, p tau₁₈₁). Predictors included motor severity (UPDRS III), depressive symptoms (BDI II), cognitive domains (memory, language, visuospatial ability, attention, executive function), and subjective cognitive decline. Multivariable analyses showed overall ADL impairment (FAQ score) and ADL item variability (ADL SD) were robustly predicted by motor severity (UPDRS III) and depressive symptoms (BDI II). Memory, language, and visuospatial abilities independently predicted less impairment and reduced variability. CSF biomarkers had no significant independent associations with functional outcomes after clinical adjustments. Notably, PD MCI patients showed higher ADL SD (M=0.417) than cognitively normal PD patients (M=0.231). In logistic regression, elevated ADL SD was the sole independent predictor of MCI (OR=2.98) and correlated with subjective cognitive decline (ρ=0.29). These findings establish ADL SD as a sensitive, independent behavioral marker of functional heterogeneity linked to cognitive status in early PD, supporting its use for risk stratification and tailored interventions. Keywords: Activities of daily living, Cerebrospinal fluid biomarkers, Depressive symptoms, Intra-individual variability, Mild cognitive impairment, Motor severity, Parkinson’s disease, Subjective cognitive decline