Objective: To clarify clinical predictors (pX) of dementia and other non-motor symptoms (NMS) in Parkinson’s disease (PD).

Background: The postural instability-gait disorder (PIGD) phenotype has been linked with NMS in PD.

Methods: A retrospective cross-sectional study evaluated 155 PD subjects assessed with the MDS-UPDRS, MMSE and Clinical Dementia Rating scales. Univariate statistics and stepwise regression were used to identify pX of total non-motor score (NMSc), including subscales of the MDS-UPDRS: bradykinesia (Brady) score; PIGD score, and PIGD minus freezing (Bal-Gait) score. A “high” (> median) NMSc was considered as an outcome variable, with odds ratios (ORs) calculated for pX, dichotomized by median values. The profile of NMS significantly associated with each pX was compared. ORs were also calculated for pX of dementia. 

Results: The NMSc was 7.8 ± 4.5 (median:7), with dementia in 29 (19%) cases. Three primary pX accounted for 45.5% of the NMSc variance: Bal-Gait score (28.5%), total levodopa equivalent dose (LD Eq) (12.9%) and Brady score (4.2%). Three redundant pX accounted uniquely for 5.5% of the NMSc variance: PD duration, age of PD onset, and motor complications score. Bal-Gait score, Brady score and PD duration all predicted both cognitive impairment and daytime sleepiness. Other NMS and their pX included: psychosis (Bal-Gait score); depressed mood (Brady score); urinary problems, orthostatic symptoms and daytime sleepiness (LD Eq); fatigue (earlier age of PD onset); and anxiety (motor complications). ORs for high NMSc ranged from 4.2 to 6.5 for a single primary pX versus 31.1 for above median scores for all three primary pX. ORs for dementia for the pX Bal-Gait score >4, Brady score ≥ 14, and PD duration > 9.6 yrs were 10.5, 7.1, and 3.6 respectively, versus 16.7 for the presence of all three pX.

Conclusions: In PD: (1) Individual NMS have one or more clinical predictors which may have additive effects.  (2) Dopaminergic (DA) pathology paralleling putamenal DA loss (Brady), non-DA pathology likely involving cortical and brainstem regions (Bal-Gait), and other changes linked to disease duration may all predispose to dementia. (3) Daytime sleepiness but not disordered sleep co-segregates with cognitive dysfunction; earlier age of PD onset may predict fatigue. (4) DA drugs other than dopamine agonists may contribute importantly to specific NMSc. (5) Neither freezing of gait nor tremor uniquely predict NMSc.

References: 1.  Ba F, Obeid M, Wieler M, et al. Parkinson Disease: The relationship between non-motor symptoms and motor phenotype.  Can J Neurol Sci. 2016;43: 261-267.

2.  van der Heeren JF, Marinus J, Martinez-Martin P, et al. Postural instability and gait are associated with severity and prognosis of Parkinson disease. Neurology 2016; 86 (24): 2243-50.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-predictors-of-dementia-and-other-non-motor-symptoms-in-parkinsons-disease/