An increased rate of longitudinal cognitive decline is observed in Parkinson's disease patients with low CSF Aß42 and an APOE ε4 allele.

OBJECTIVE: Low concentrations of cerebrospinal fluid (CSF) amyloid-beta (Aß-42) are associated with increased risk of cognitive decline in Parkinson's disease (PD). We sought to determine whether APOE genotype modifies the rate of cognitive decline in PD patients with low CSF Aß-42 compared to patients with normal levels. METHODS: The Parkinson's Progression Markers Initiative is a longitudinal, ongoing study of de novo PD participants, which includes APOE genotyping, CSF Aß-42 determinations, and neuropsychological assessments. We used linear mixed effects models in three PD groups (PD participants with low CSF Aß at baseline, PD participants with normal CSF Aß, and both groups combined). Having at least one copy of the APOE ɛ4 allele, time, and the interaction of APOE ɛ4 and time were predictor variables for cognitive change, adjusting for age, gender and education. RESULTS: 423 de novo PD participants were followed up to 5 years with annual cognitive assessments. 103 participants had low baseline CSF Aß-42 (39 APOE ε4+, 64 APOE ε4-). Compared to participants with normal CSF Aß-42, those with low CSF Aß-42 declined faster on most cognitive tests. Within the low CSF Aß-42 group, APOE ε4+ participants had faster rates of decline on the Montreal Cognitive Assessment (primary outcome; 0.57 points annual decline, p = .005; 5-year standardized change of 1.2) and the Symbol Digit Modalities Test (1.4 points annual decline, p = .002; 5-year standardized change of 0.72). DISCUSSION: PD patients with low CSF Aß-42 and APOE ε4+ showed a higher rate of cognitive decline early in the disease. Tests of global cognition (Montreal Cognitive Assessment) and processing speed (Symbol Digit Modalities Test) were the most sensitive to early cognitive decline. Results suggest that CSF Aß-42 and APOE ε4 might interact to promote early cognitive changes in PD patients.

Comparative sensitivity of the MoCA and Mattis Dementia Rating Scale-2 in Parkinson's disease.

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.

Domain-specific accuracy of the Montreal Cognitive Assessment subsections in Parkinson's disease.

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.