Non-motor correlates of anxiety in de novo Parkinson’s disease: a cross-sectional study with exploratory subgroup analyses

Abstract

Anxiety is a prevalent early non-motor symptom of Parkinson’s disease (PD), but its clinical correlates remain poorly defined in de novo , drug-naïve patients. This retrospective cross-sectional study enrolled 284 medication-naïve de novo PD patients and 147 age- and sex-matched healthy controls to identify non-motor correlates of anxiety after adjustment for demographic and motor covariates, and explore potential subgroup heterogeneity. Anxiety was assessed with the Hamilton Anxiety Rating Scale; multivariate logistic regression and prespecified stratified analyses by age, sex, disease duration, Hoehn-Yahr stage and motor severity were performed. Clinically significant anxiety was detected in 44.0% of PD patients versus 8.1% of controls ( p  < 0.001), with psychic anxiety as the dominant subtype. After multivariate adjustment, higher depressive symptom scores were positively associated with anxiety (OR = 1.386), whereas better sleep quality (OR = 0.965) and intact olfactory identification (OR = 0.815) were negatively associated with anxiety; motor severity showed no significant association after multivariable adjustment. Exploratory subgroup analyses revealed heterogeneous patterns of sleep and olfactory correlates across clinical strata. The three-factor predictive model yielded an overall classification accuracy of 84.81%. These findings indicate that non-motor abnormalities, rather than motor impairment, are associated with anxiety in early PD after adjustment for demographic and motor covariates. The distinct correlative patterns across subgroups provide preliminary clinical clues for the heterogeneous neurodegenerative processes underlying PD-related anxiety, and support routine screening of depressive, sleep and olfactory symptoms to facilitate anxiety risk stratification at initial diagnosis.