Risk of Parkinson's disease dementia related to level I MDS PD-MCI.

BACKGROUND: The International Parkinson and Movement Disorders Society criteria for mild cognitive impairment in PD need validation. The objectives of this present study were to evaluate prognostic validity of level I (abbreviated) International Parkinson and Movement Disorders Society mild cognitive impairment in PD criteria for development of PD dementia and compared them with level II (comprehensive) criteria. METHODS: We analyzed data from 8 international studies (1045 patients) from our consortium that included baseline data on demographics, motor signs, depression, detailed neuropsychological testing, and longitudinal follow-up for conversion to Parkinson's disease dementia. Survival analysis evaluated their contribution to the hazard of Parkinson's disease dementia. RESULTS: Level I mild cognitive impairment in PD, increasing age, male sex, and severity of PD motor signs independently increased the hazard of Parkinson's disease dementia. Level I and level II mild cognitive impairment in PD classification had similar discriminative ability with respect to the time to Parkinson's disease dementia. CONCLUSIONS: Level I mild cognitive impairment in PD classification independently contributes to the hazard of Parkinson's disease dementia. This finding supports the prognostic validity of the abbreviated mild cognitive impairment in PD criteria. © 2019 International Parkinson and Movement Disorder Society.

Detecting Mild Cognitive Deficits in Parkinson's Disease: Comparison of Neuropsychological Tests.

BACKGROUND: Numerous neuropsychological tests and test versions are used in Parkinson's disease research, but their relative capacity to detect mild cognitive deficits and their comparability across studies are unknown. The objective of this study was to identify neuropsychological tests that consistently detect cognitive decline in PD across studies. METHODS: Data from 30 normed neuropsychological tests across 20 international studies in up to 2908 nondemented PD patients were analyzed. A subset of 17 tests was administered to up to 1247 healthy controls. A 2-step meta-analytic approach using standardized scores compared performance in PD with normative data. RESULTS: Pooled estimates of the differences between PD and site-specific healthy controls identified significant cognitive deficits in PD patients on 14 test scores across 5 commonly assessed cognitive domains (attention or working memory, executive, language, memory, and visuospatial abilities), but healthy control performance was statistically above average on 7 of these tests. Analyses based on published norms only, as opposed to direct assessment of healthy controls, showed high between-study variability that could not be accounted for and led to inconclusive results. CONCLUSIONS: Normed neuropsychological tests across multiple cognitive domains consistently detect cognitive deficits in PD when compared with site-specific healthy control performance, but relative PD performance was significantly affected by the inclusion and type of healthy controls versus the use of published norms only. Additional research is needed to identify a cognitive battery that can be administered in multisite international studies and that is sensitive to cognitive decline, responsive to therapeutic interventions, and superior to individual cognitive tests. © 2018 International Parkinson and Movement Disorder Society.

CSF Aß42 predicts early-onset dementia in Parkinson disease.

OBJECTIVE: To test in vivo the proposal from clinicopathologic studies that ß-amyloid (Aß) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF Aß and related measures as early prognostic biomarkers of dementia in an incident PD cohort. METHODS: We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of Aß42, Aß40, and Aß38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of Aß42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria. RESULTS: CSF levels of Aß42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p = 0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other markers. Low Aß42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (≥ 85%), with hazard ratios of 9.9 (95% confidence interval 2.3-43.5, p = 0.002) for Aß42ECL <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for Aß42ELISA <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. Aß42 reductions tended to precede the onset of PD-MCI that progressed to dementia. CONCLUSIONS: These in vivo data support the role of Aß pathology in the etiology and highlight the potential utility of CSF Aß42 as an early prognostic biomarker of dementia associated with PD.