Disease progression in Parkinson's disease patients with mild cognitive impairment: 5-year longitudinal study from the early Parkinson's disease longitudinal Singapore (PALS) cohort

Abstract

Aim: To investigate motor, non-motor and cognitive progression in early Parkinson's disease (PD) patients with Mild Cognitive Impairment (MCI).

Methods: PD patients were recruited within 1 year of diagnosis and were classified into PD-MCI group and PD with normal cognition (PD-NC) group. H&Y staging scale, MDS-UPDRS part III were used to assess disease severity and motor progression. Non-motor symptom scale (NMSS) was used to evaluate the NMS progression. Cognitive progression was assessed from 5 cognitive domains. Annual progression changes in the longitudinal outcomes were examined via linear mixed model with random intercept effect. False discovery rate (FDR) method was performed to control for multiple testing comparison and q-value was calculated. We set the threshold of q-values as 0.1.

Result: A total of 205 PD patients, including 107 PD-MCI and 98 PD-NC patients were assessed prospectively over a 5-year period. PD-MCI patients, compared to PD-NC group, had a significantly higher progression rate in H&Y score (0.11 vs. 0.06, p=0.03, q=0.08), MDS-UPDRS motor score (3.11 vs. 1.90 p<0.001, q=0.06) and postural instability gait difficulty (PIGD) score (0.40 vs. 0.20, p=0.02, q=0.07). PD-MCI group also exhibited significantly faster deterioration in NMSS perceptual domain (PD-MCI vs. PD-NC: 0.38 vs. -0.04, p=0.01, q=0.06) and cognitive visuospatial domain (PD-MCI vs. PD-NC: 0.13 vs. -0.06, p=0.048, q=0.09) after adjustment for confounders and multiple comparisons.

Conclusions: PD-MCI patients had faster decline in motor functions, visuo-perceptual and visuospatial performance. These findings provide a more comprehensive prognosis of PD-MCI, which could be helpful for clinician to manage PD-MCI patients.

Keywords: Parkinson’s disease; disease progression; mild cognitive impairment.

Figure 1

Motor progression between PD-MCI and PD-NC. (A) Progression slopes of H&Y score in PD-MCI and PD-NC group were 0.11 vs. 0.06, p=0.03. (B) Progression slopes of UPDRS motor score in PD-MCI and PD-NC group were 3.11 vs. 1.90 p=0.00. (C) Progression slopes of PIGD score in PD-MCI and PD-NC group were 0.45 vs. 0.24, p=0.02. Longitudinal linear mixed model was performed to compare the progression slopes of motor outcomes between PD-MCI and PD-NC group; analysis has been adjusted for age of diagnosis, sex and education year. Abbreviations: H&Y: Modified Hoehn and Yahr staging scale; MDS-UPDRS: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; PIGD: Postural Instability and Gait Disorder.

Figure 2

Non-motor progression between PD-MCI and PD-NC. (A) Progression slopes of NMSS total score in PD-MCI and PD-NC group were 3.74 vs. 2.06, p=0.14. (B) Progression slopes of NMSS domain 4 score in PD-MCI and PD-NC group were 0.38 vs. -0.04, p=0.01. Longitudinal linear mixed model was performed to compare the progression slopes of non-motor outcomes between PD-MCI and PD-NC group; analysis has been adjusted for age of diagnosis, sex and education year. Abbreviations: NMSS: non-motor symptom scale; NMSS domain 4 (perceptual problems/hallucinations).

Figure 3

Cognitive progression between PD-MCI and PD-NC. (A) Progression slopes of MoCA score in PD-MCI and PD-NC group were -0.36 vs. -0.21, p=0.21. (B) Progression slopes of standardised visuospatial score in PD-MCI and PD-NC group were -0.13 vs. -0.06, p=0.048. Longitudinal linear mixed model was performed to compare the progression slopes of cognitive outcomes between PD-MCI and PD-NC group; analysis has been adjusted for age of diagnosis, sex and education year. Abbreviations: MoCA score: Montreal Cognitive Assessment score.