Baseline cognitive profile is closely associated with long-term motor prognosis in newly diagnosed Parkinson’s disease

Objectives: To investigate the association between cognitive function at baseline and the progression of motor disability in Parkinson’s disease (PD). Methods: We consecutively enrolled 257 drug-naïve patients with early-stage PD (follow-up > 2 years) who underwent a detailed neuropsychological test at initial assessment. Factor analysis was conducted to yield four cognitive function factors and composite scores thereof: Factor 1 (visual memory/visuospatial), Factor 2 (verbal memory), Factor 3 (frontal/executive), and Factor 4 (attention/working memory/language). The global cognitive composite score of each patient was calculated based on these factors. Subsequently, we assessed the effect of baseline cognitive function on long-term motor outcomes, namely levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and rate of longitudinal increases in levodopa-equivalent dose (LED). Results: Cox regression analysis demonstrated that higher Factor 3 (frontal/executive) composite scores (i.e., better cognitive performance) were associated with early development of LID [hazard ratio (HR), 1.507; p = 0.003], whereas higher Factor 1 (visual memory/visuospatial) composite scores (i.e., better cognitive performance) were associated with a lower risk for FOG (HR 0.683; p = 0.017). We noted that higher global cognitive composite scores were associated with a lower risk for developing FOG (HR 0.455; p = 0.045). The linear mixed model demonstrated that higher global cognitive composite scores and better cognitive performance in visual memory/visuospatial function were associated with slower longitudinal increases in LED. Conclusions: These findings suggest that baseline cognitive profiles have prognostic implications on several motor aspects in patients with PD.