Combined impact of depressive symptoms and mild cognitive impairment on Parkinson's disease progression

To investigate the joint associations of depressive symptoms and mild cognitive impairment (MCI) with longitudinal cognitive and clinical progression in Parkinson's disease (PD).

A cohort of 487 non-demented Parkinson's disease patients was categorized into normal cognition without depressive symptoms (ndNC), normal cognition with depressive symptoms (dNC), MCI without depressive symptoms (ndMCI), and MCI with depressive symptoms (dMCI) groups. Cognitive, motor, non-motor, and quality-of-life outcomes were assessed annually for up to 2.39 years using adjusted linear mixed-effects models. Factorial and continuous BDI sensitivity analyses were also performed.

At baseline, the dMCI group showed poorer executive, language, and visuospatial performance than ndMCI patients (P = 0.003, P = 0.014, P = 0.014, respectively). Longitudinally, dMCI showed faster global cognitive decline than ndNC and dNC patients, faster language decline than ndNC patients, and faster visuospatial decline than all other groups. Quality of life also worsened faster in dMCI than in ndNC and ndMCI. The Time×depressive symptoms×MCI interaction remained significant after FDR correction for visuospatial decline. For global cognition, the corresponding interaction was nominally significant but did not remain significant after FDR correction (P = 0.036; FDR-adjusted P = 0.054). Continuous BDI analysis further supported an association between greater depressive symptom burden and faster global cognitive decline among patients with MCI.

Coexisting depressive symptoms and MCI identified a clinically vulnerable subgroup, particularly for visuospatial decline. Evidence for an interaction affecting global cognition remained suggestive rather than conclusive. These findings suggest that assessment of depressive symptoms may be clinically relevant in Parkinson's disease, particularly among patients with cognitive impairment.