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By Claire Henchcliffe, MD
Associate Professor of Neurology and Neuroscience, Weill Cornell Medical College
Dr. Henchcliffe reports she is on the speakers bureau and advisory board for GE, Teva Pharmaceutical Industries, and UCB; advisory board for Allergan and USWorldmeds; receives grant/research support from Biogen and Kaneka; and does CME program development and presentation for MedIQ.
Synopsis: The Montreal Cognitive Assessment and Mini-Mental Status Exam demonstrated baseline deficits in early Parkinson’s disease. Male sex, motor, and non-motor measures including depression and hyposmia were associated with cognitive dysfunction.
Source: Hu MT, et al. Predictors of cognitive impairment in an early stage Parkinson’s disease cohort. Mov Disord 2014;29:351-359.
This study focused on clinical rating scales measuring cognitive function in individuals with Parkinson’s disease (PD) followed in the "Oxford Discovery Cohort," all within 3.5 years of diagnosis. Baseline data were compared with 144 healthy controls, and longitudinal data over 18 months were available for 155 PD subjects. PD subjects were slightly older than controls (67.8 ± 9.4 vs 63.5 ± 8.9 years; P < 0.001), with less education (13.6 ± 3.5 vs 15.1 ± 3.5 years; P < 0.001), and were more likely to be men (61.3% vs 35.5%). Mean PD duration was 1.5 ± 1.0 years, motor Unified PD Rating Scale (UPDRS) score was 26.8 ± 11.0, and Hoehn and Yahr score was 1.9 ± 0.5, all reflecting early stage PD. There was a significant reduction in PD compared with controls at baseline in Modified Mini-Mental Status Examination (MMSE) scores (27.3 ± 2.2 vs 28.4 ± 1.8, respectively; P = 0.001), and Montreal Cognitive Assessment (MoCA) scores (24.9 ± 3.5 vs 27.1 ± 2.2, respectively; P < 0.001). Using diagnostic thresholds for the MMSE, 7.2% of PD subjects had either PD-Mild Cognitive Impairment (PD-MCI) or PD-Dementia (PDD) compared with just 1.4% of controls. However, MoCA scores using diagnostic thresholds found 14.2% with PD-MCI and 16.3% with PDD in the PD group, vs 6.4% and 0.7%, respectively, in the control group. Strong predictors of worse MoCA scores in the PD group at baseline included older age, male sex, and fewer educational years. Multivariable linear regression analysis also revealed a number of motor and non-motor features associated with MoCA scores: Hoehn and Yahr stage; annualized UPDRS score; Timed Up and Go test; balance, anxiety, and depression rating scales; and hyposmia. Only MoCA scores significantly declined over 18 months follow-up in the PD group (from 25.7 ± 3.0 to 24.9 ± 3.4; P < 0.001), with a shift from normal to PD-MCI in 33 subjects (21.3%), and from PD-MCI to PDD in 7 subjects (4.5%). Only 51 (32.9%) remained in the normal range. Changes were driven by subscores for memory, orientation, and semantic fluency.
The occurrence of cognitive impairment in early PD has been well established over the last few years, and Movement Disorder Society Task Force guidelines on PD-MCI were published in 2012. However, detailed understanding of its heterogeneity, impact, progression, and associations is lacking. This study, therefore, moves the field ahead in using prospectively collected data in a well-characterized PD cohort. In this early PD population, the investigators found that PD-MCI was common, but using MoCA scores at diagnostic thresholds, 16.3% of this early PD cohort were already classified as having PDD. As much as the initial diagnostic data are alarming, so is the longitudinal aspect of the study. Almost 26% of patients progressed across MoCA cutoff values used for classification. This suggests that we should be following our patients in clinic using MoCA ratings, even in early PD. Where does the MMSE fit into patient assessment? MMSE classification at diagnostic thresholds found fewer PD-MCI and PDD scores; the authors suggest this is due to lower sensitivity of the MMSE, although they acknowledge that it may also be due to over-classification of MCI and PDD by MoCA scores. MMSE longitudinal changes over 18 months were also difficult to explain: 24% of PD subjects deteriorated but 25% improved, suggesting a degree of misclassification. Although the present study suggests using the MoCA scale will be more helpful as a short "clinic-friendly" tool to follow cognition in PD, it remains difficult to reconcile data with a recent publication in the same journal by Lessig et al.1 These investigators found that MMSE but not MoCA significantly declined over a time span of 3 years. Hu and colleagues suggest this is due to a difference in disease duration between the two studies, and that MMSE might be more sensitive in later PD. In the end, it will take further follow up and careful clinical evaluation to clarify how well the MoCA and MMSE scores in this study correlate with clinical diagnosis, and the finding of PDD in this cohort raises the question of diagnostic accuracy within the cohort.
Nonetheless, in addition to providing valuable information on use of these brief bedside tests in early PD, the study identified a number of interesting associations with cognition, among them male sex. This, therefore, adds to a growing literature on sex differences in PD presentation. Worse motor function and olfaction were also associated with worse cognitive measures. Whether these have specific neurochemical underpinnings in common, such as cholinergic involvement, or whether cognitive deficits reflect more "global" pathology remains to be seen. This study supports use of a simple tool in the clinic, that when better described, may aid in assessing prognosis and tracking disease progression: both of which are critical and unmet needs.