Baseline predictors for progression 4 years after Parkinson's disease diagnosis in the De Novo Parkinson Cohort (DeNoPa).

OBJECTIVES: The objectives of this study were to investigate (1) the annual rate of progression of motor and cognitive symptoms and (2) baseline predictors of different modalities for this progression in early Parkinson's disease (PD) when compared with healthy controls. METHODS: A total of 135 de novo PD and 109 healthy controls (of the De Novo Parkinson cohort) were investigated at baseline and after 24 and 48 months. To delineate motor progression and cognitive decline, the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) and the Mini-Mental Status Examination (MMSE) were selected. Baseline variables used to predict progression included sociodemographic factors, comorbidities, motor/nonmotor symptoms, polysomnography, MRI, and laboratory biomarkers in serum and CSF. RESULTS: Symptoms worsened over 4 years in PD with an annual change of 1.8 points on the MDS-UPDRS III and 0.2 points on the MMSE. Baseline predictors of worse progression of motor symptoms in PD included male sex, orthostatic blood pressure drop, diagnosis of coronary artery disease, arterial hypertension, elevated serum uric acid, and CSF neurofilament light chain. Predictors of cognitive decline in PD included previous heavy alcohol abuse, current diagnoses of diabetes mellitus, arterial hypertension, elevated periodic limb movement index during sleep, decreased hippocampal volume by MRI, higher baseline levels of uric acid, C-reactive protein, high density lipoprotein (HDL) cholesterol, and glucose levels. CONCLUSION: Cardiovascular risk factors, deregulated blood glucose, uric acid metabolism, and inflammation were identified as risk markers for faster disease progression. Our panel of risk parameters needs validation during our continuing follow-up and also in independent patient cohorts. © 2018 International Parkinson and Movement Disorder Society.

Validation of conversion between mini-mental state examination and montreal cognitive assessment.

INTRODUCTION: Harmonizing data across cohorts is important for validating findings or combining data in meta-analyses. We replicate and validate a previous conversion of MoCA to MMSE in PD. METHODS: We used five studies with 1,161 PD individuals and 2,091 observations measured with both the MoCA and MMSE. We compared a previously published conversion table using equipercentile equating with log-linear smoothing to our internally derived scores. RESULTS: Both conversions found good agreement within and across the studies when comparing true and converted MMSE (mean difference: 0.05; standard deviation: 1.84; median difference: 0; interquartile range: -1 to 1, using internal conversion). CONCLUSIONS: These results show that one can get a reliable and valid conversion between two commonly used measures of cognition in PD studies. These approaches need to be applied to other scales and domains to enable large-scale collaborative analyses across multiple PD cohorts.

Dynamic interplay of cognitive functioning and depressive symptoms in patients with Parkinson's disease.

OBJECTIVE: We examine the trajectories of and the dynamic interplay between cognitive functioning and depressive symptoms in patients with Parkinson's disease (PD) in comparison to healthy controls (HC) from an intraindividual perspective. METHOD: The DeNoPa study is a single-center, observational, longitudinal study with biennial follow-ups over 8 years. The present analyses are based on 123 PD (79 male) and 107 HC (64 male) with a mean age of 64.1 years (SD = 8.3). PD and HC completed a battery of neuropsychological tests and scales assessing depressive symptoms. We used a random-intercept cross-lagged panel model (RI-CLPM) to study their trajectories and the dynamic interplay. RESULTS: Cognitive abilities of PD were on average d = -0.67 worse at baseline and d = -1.22 at 8-years follow-up in comparison to HC. Depressive symptoms in PD showed large variability and followed a U-shaped trajectory. From an intraindividual perspective, greater impairments in cognitive abilities were subsequently associated with increased depressive symptoms (b = -0.60, p = .03), whereas the effect in the opposite direction was not significant. CONCLUSIONS: We found indication that a decline on a global composite scale of cognition can be seen as a precursor of depressive symptoms in patients with PD. To counter cognitive losses and the subsequent mood deterioration, patient education and early cognitive (and behavioral) enrichment seem promising candidates for treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Monitoring of 30 marker candidates in early Parkinson disease as progression markers.

OBJECTIVE: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106). METHODS: Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). RESULTS: A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09-0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06-0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24-0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25-0.64), and RBD by PSG (d 0.37; CI 0.19-0.55) as well as VBM units of cortical gray matter (d -0.2; CI -0.3 to -0.09) and hippocampus (d -0.15; CI -0.27 to -0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d -0.19; CI -0.36 to -0.02) and 2 depression scales (Beck Depression Inventory d -0.18; CI -0.36 to 0; Montgomery-Åsberg Depression Rating Scale d -0.26; CI -0.47 to -0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants. CONCLUSIONS: Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression.

Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort.

OBJECTIVE: To determine nonmotor signs (NMS) and evaluate the utility of several diagnostic tools in patients with de novo Parkinson disease (PD). METHODS: This is a large single-center study of the DeNoPa cohort, including frequency-matched healthy controls. This study covers motor signs, NMS, and a combination of diagnostic tests including olfactory testing, transcranial sonography of substantia nigra (TCS), and polysomnography (PSG). We report the frequency and characteristics of NMS and the outcomes of nonmotor tests at the time of diagnosis. RESULTS: Cross-sectional analyses of baseline investigations identified significant differences in the NMS Questionnaire (NMSQuest) and the Scopa-AUT Gastrointestinal score in 159 drug-naïve PD patients vs 110 controls. In addition, patients with PD showed reduced olfactory function, hyperechogenicity on TCS, and higher frequency of REM sleep behavior disorder (RBD). In exploring predictive markers, we found that the combination of several investigations, i.e., the NMSQuest, Scopa-AUT Gastrointestinal score, and Smell Identification Test reached an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI] 0.878-0.948). With the addition of serum cholesterol and mean heart rate values, the AUC value reached 0.919 (95% CI 886-0.953); when TCS and PSG were added, the AUC increased to 0.963 (95% CI 0.943-0.982). CONCLUSIONS: We show feasibility and utility of standardized data acquisition in a large, single-center cohort of patients with de novo PD and matched healthy controls. The baseline results from our prospective investigations reached a value of >0.9 sensitivity and specificity for biological markers when we added routine laboratory investigations and quantified nonmotor features including sleep.