Objective: Cognitive impairments in Parkinson disease (PD) are thought to be caused in part by dopamine dysregulation. However, even when nigrostriatal dopamine neuron loss is severe enough to cause motor symptoms, many patients remain cognitively unimpaired. It is unclear what brain mechanisms allow these patients to remain cognitively unimpaired despite substantial dopamine dysregulation. Methods: Thirty-one cognitively unimpaired PD participants off dopaminergic medications were scanned using functional magnetic resonance imaging while they performed a working memory task, along with 23 controls. We first compared the PD off medication (PD_OFF) group with controls to determine whether PD participants engage compensatory frontostriatal mechanisms during working memory. We then studied the same PD participants on dopaminergic medications to determine whether these compensatory brain changes are altered with dopamine. Results: Controls and PD showed working memory load-dependent activation in the bilateral putamen, anterior-dorsal insula, supplementary motor area, and anterior cingulate cortex. Compared to controls, PD_OFF showed compensatory hyperactivation of bilateral putamen and posterior insula, and machine learning algorithms identified robust differences in putamen activation patterns. Compared to PD_OFF, the PD on medication group showed reduced compensatory activation in the putamen. Loss of compensatory hyperactivation on dopaminergic medication correlated with slower performance on the working memory task and slower cognitive speed on the Symbol Digit Modality Test. Interpretation: Our results provide novel evidence that PD patients maintain normal cognitive performance through compensatory hyperactivation of the putamen. Dopaminergic medication downregulates this hyperactivation, and the degree of downregulation predicts behavior. Identifying cognitive compensatory mechanisms in PD is important for understanding how some patients maintain intact cognitive performance despite nigrostriatal dopamine loss.

Objective The Montreal Cognitive Assessment (MoCA) is among the most widely adopted screening tools for cognitive impairment because it includes tests in multiple domains and is available in 55 languages. The MoCA is often the only formal cognitive assessment available when comprehensive neuropsychological testing is not practical, such as rural clinical settings or large retrospective and multi-lingual research settings. However, the MoCA domain-specific subsections have never been formally assessed for sensitivity or specificity. Therefore, in Parkinson’s disease, we examined whether the subsections of the MoCA could identify cognitive impairment within specific cognitive domains. Methods We administered a comprehensive neuropsychological battery to 85 Parkinson’s disease participants, who were then categorized as with or without cognitive impairment, with respect to global cognition and in five cognitive domains. We then assessed the domain-specific categorization of the MoCA subsections compared to the full neuropsychology battery. Results All MoCA subsections predicted impairment in their respective cognitive domain. However, the executive subsection showed the highest sensitivity and specificity (89.3% and 82.5%, respectively), followed by visuospatial (93.3% and 45.7%, respectively) and memory (84.6% and 56.5%, respectively). Conclusion The MoCA is a useful screening tool for PD global cognitive and executive functions. The MoCA is also highly sensitive to visuospatial and memory impairment, but with limited specificity and accuracy these subsections should be interpreted with caution.

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Background Clinicians and researchers commonly use global cognitive assessments to screen for impairment. Currently there are no published studies directly comparing the sensitivity and specificity of the Montreal Cognitive Assessment and Mattis Dementia Rating Scale‐2 in PD. The objective of this study was to identify the relative sensitivity and specificity of the Montreal Cognitive Assessment and Mattis Dementia Rating Scale‐2 in PD. Methods The Montreal Cognitive Assessment and Mattis Dementia Rating Scale‐2 were administered to training and validation cohorts. Cutoff scores were determined within the training cohort (n = 85) to optimize sensitivity and specificity for cognitive impairment and were applied to an independent validation cohort (n = 521). Results The Montreal Cognitive Assessment was consistently sensitive across training and validation cohorts (90.0% and 80.3%, respectively), whereas the Mattis Dementia Rating Scale‐2 was not (87.5% and 60.3%, respectively). In individual domains, the Montreal Cognitive Assessment remained sensitive to memory and visuospatial impairments (91.9% and 87.8%, respectively), whereas the Mattis Dementia Rating Scale‐2 was sensitive to executive impairments (86.2%). Conclusion The Montreal Cognitive Assessment and Mattis Dementia Rating Scale‐2 demonstrated individual strengths. Future work should focus on developing domain‐specific cognitive screening tools for PD. © 2018 International Parkinson and Movement Disorder Society

Our data provide further evidence that PD_OFF and PD_ON participants engage different cortical and subcortical systems to achieve similar levels of cognitive performance as HC. Crucially, our findings demonstrate dopamine-related dissociation in brain activation between cortical and subcortical regions, and provide novel support for the dopamine overdose hypothesis.

Both neuropsychological tests of executive functioning and the Frontal Systems Behavior Scale (FrSBe) consistently predict instrumental activity-of-daily-living capacity. However, the nature of the predictive relationship between the FrSBe and neuropsychological tests of executive functioning has received limited attention. The current study was designed to assess the incremental validity of the FrSBe in predicting instrumental activity-of-daily-living functioning when added to comprehensive testing of executive functioning in a sample of 100 adult general neuropsychological referrals. A composite measure of executive test performance was calculated, and a family member completed the FrSBe and an instrumental activity-of-daily-living measure. Stepwise multiple regression analysis using the executive composite measure and the FrSBe accounted for 44% of the variance in instrumental activity capacity, and the addition of the FrSBe increased predictive ability by approximately 50%. The current results also indicate that FrSBe Scale E is more important as a predictor of instrumental activity capacity than the two self-regulation measures, Scale A and Scale D.

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