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The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer's or Parkinson's disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials., (© 2022. The Author(s).)

Objectives: We aimed to disclose the relationship between restless leg syndrome (RLS) and antiparkinsonian treatment, and its effect on quality of life (QoL) in patients with Parkinson's disease (PD)., Background: Previous studies documented the prevalence of RLS among patients with PD to be higher than in the general population, but conclusions regarding the aetiology and impact were contradictory., Methods: We examined 101 patients with idiopathic PD. All participants completed the five-dimension/five-level-EuroQoL questionnaire (EQ-5D-5L) and the International Restless-Legs-syndrome-study-group rating Scale (IRLS)., Results: The prevalence of RLS was 22.77 %. There were no statistically significant differences in levodopa or dopamine agonists (DA) doses between RLS-positive and negative participants. However, the use of levodopa as the last night-time medication was connected with a higher risk of RLS (OR=2.049, p=0.041). There was significantly lower prevalence of RLS in patients after surgical treatment for PD (p=0.024). Participants with RLS were at a greater risk for sleep disturbances (OR=3.866, p=0.023) and excessive daytime sleepiness (OR=7.202, p<0.001). Greater RLS symptoms were associated with worse QoL (higher IRLS score predicted higher EQ5D5L score, p=0.023)., Conclusion: RLS is prevalent among PD patients and night-time dopaminergic over-excitation with levodopa plays an important role in its pathogenesis. Since the symptoms of RLS are associated with decreased QoL, early accurate diagnosis and appropriate adjustment of dopaminergic therapy can lead to immediate relief from RLS symptoms and to QoL improvement (Tab. 4, Fig. 1, Ref. 34).

Objective: Longitudinal assessment of cognitive and emotional functioning in patients with Parkinson's disease (PD) is helpful in tracking progression of the disease, developing treatment plans, evaluating outcomes, and educating patients and families. Determining whether change over time is meaningful in neurodegenerative conditions, such as PD, can be difficult as repeat assessment of neuropsychological functioning is impacted by factors outside of cognitive change. Regression-based prediction formulas are one method by which clinicians and researchers can determine whether an observed change is meaningful. The purpose of the current study was to develop and validate regression-based prediction models of cognitive and emotional test scores for participants with early-stage idiopathic PD and healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI)., Methods: Participants with de novo PD and HC were identified retrospectively from the PPMI archival database. Data from baseline testing and 12-month follow-up were utilized in this study. In total, 688 total participants were included in the present study (NPD = 508; NHC = 185). Subjects from both groups were randomly divided into development (70%) and validation (30%) subsets., Results: Early-stage idiopathic PD patients and healthy controls were similar at baseline. Regression-based models were developed for all cognitive and self-report mood measures within both populations. Within the validation subset, the predicted and observed cognitive test scores did not significantly differ, except for semantic fluency., Conclusions: The prediction models can serve as useful tools for researchers and clinicians to study clinically meaningful cognitive and mood change over time in PD., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: Evaluate neuropsychological test performance in depressed patients with early-stage Parkinson's disease., Method: Data from 422 participants from the Parkinson's Progression Marker Initiative were examined. The Geriatric Depression Scale-15 was used to categorize depressed and non-depressed participants. Neuropsychological tests measured verbal learning/memory, processing speed, visuospatial ability, verbal fluency, and working memory. Demographic and clinical variables were compared using independent samples t tests and chi-square analyses.Linear regression models were fit to adjust for age, years of education, and symptom duration., Results: The non-depressed group (n = 280) was significantly older; t(246.08) = 2.25, p = .026 and had higher education; t(420) = 2.35, p = .019; and longer duration of PD symptoms; t(170.58) = -2.13, p = .035 than the depressed group (n = 142). The non-depressed group performed better on a working memory task than the depressed group, t(420) = 2.05, p = .041, but the results did not appear to be of clinical significance. There was no significant difference between other cognitive domains. The results were not influenced by age, education, or disease duration., Conclusions: Among patients with early-stage, untreated Parkinson's disease, depression does not appear to affect neuropsychological test performance. Clinicians should demonstrate caution in over-interpreting the influence of depression on cognition in this population., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: To examine neuropsychological test performance among individuals clinically diagnosed with Parkinson's disease (PD) without evidence of dopaminergic deficiency on [123]I-CIT single photon emission computed tomography imaging., Methods: Data were obtained from the Parkinson's Progression Marker Initiative. The sample included 59 participants with scans without evidence of dopaminergic deficiency (SWEDD), 412 with PD, and 114 healthy controls (HC). Tests included Judgment of Line Orientation, Letter-Number Sequencing, Symbol Digit Modalities, Hopkins Verbal Learning Test-Revised, and Letter and Category Fluency. Multivariate analysis of variance was used to compare standardized scores between the groups., Results: There was a statistically significant difference in performances between the groups, F(14,1155)=5.04; p<.001; partial η2=.058. Pairwise comparisons revealed significant differences in Category Fluency between SWEDD (M=0.22; SD=1.08) and HC (M=0.86; SD=1.15) and in Symbol Digit Modalities Test performance between SWEDD (M=45.09; SD=11.54) and HC (M=51.75; SD=9.79). No significant differences between SWEDD and PD were found. Using established criteria, approximately one in four participants in the SWEDD and PD groups met criteria for mild cognitive impairment (MCI)., Conclusions: Individuals with SWEDD demonstrate significantly worse mental processing speed and semantic fluency than HC. The neuropsychological test performances and rates of MCI were similar between the SWEDD group and PD groups, which may reflect a common pathology outside of the nigrostriatal pathway. (JINS, 2018, 24, 646-651).

Objective: The objective of this study was to examine the impact of different methods of standardizing cognitive data in the Parkinson's Progression Marker Initiative., Methods: Cognitive data from 423 participants with Parkinson's disease were included (age = 61.7 [9.7], education = 15.6 [3.0]). Internal norms were calculated using the group mean and standard deviation of the healthy control group. Published norms were compared to the overall group mean of and to age-stratified norms from healthy controls for each neuropsychological test over 4 visits. Rates of mild cognitive impairment were calculated using established criteria., Results: The use of internal norms resulted in lower standardized scores than published norms on all tests with the exception of memory and processing speed (P ≤ .001). Individuals were 1.5 to 2.1 times more likely to be diagnosed with mild cognitive impairment using internal norms than published norms., Conclusions: Standardization approaches with cognitive data are not interchangeable. Selection of a normative comparison group impacts research and clinical interpretations of cognitive data. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)

Background/aims: Mild cognitive impairment (MCI) is present in up to 34% of patients with early-stage Parkinson disease (PD); however, it is difficult to detect subtle impairment without objective cognitive testing., Methods: Data were obtained from the Parkinson Progression Marker Initiative. All 341 participants were administered the Montreal Cognitive Assessment (MoCA) and a brief neuropsychological battery. Participants were classified as PD-MCI if MoCA was <26 or if they scored ≥1 standard deviation below the normative mean in 2 or more domains, based upon established criteria. The sensitivity/specificity for the clinical detection of PD-MCI was determined., Results: Overall accuracy for clinical detection of PD-MCI was 67.4%. Although clinical determination was highly specific (96.3%; 95% confidence interval [CI]: 0.92-0.98), sensitivity was poor (32.0%; 95% CI: 0.25-0.40)., Conclusion: Identifying MCI in early-stage PD based on clinical interview alone appears to be insufficient. The inclusion of objective cognitive tests allowing for normative sample comparisons is needed to increase the detection of cognitive impairment in this population.

Objective and Background: More than 10% of patients clinically diagnosed with Parkinson disease demonstrate normal dopamine uptake on dopamine transporter single-photon emission computed tomography (DaTscan), but little is known about how cognitive function differs between patients with dopamine deficiency on DaTscan and patients with scans without evidence of dopaminergic deficit (SWEDD). We compared the cognitive function of these two groups of patients over 2 years., Methods: We retrospectively analyzed data obtained from the Parkinson's Progression Markers Initiative on 309 participants clinically diagnosed with idiopathic Parkinson disease who had scored in the normal range on the Montreal Cognitive Assessment at baseline and had completed 1- and 2-year follow-up visits. We compared the Montreal Cognitive Assessment scores at 1 and 2 years between the 42 participants with SWEDD and the 267 with dopamine deficiency., Results: Mean cognitive scores did not differ significantly between groups at 1 year, but at 2 years the participants with SWEDD performed more poorly. At 2 years, 31% of the participants with SWEDD versus 15% of those with dopamine deficiency had statistically reliable cognitive impairment., Conclusions: This study provides evidence that some individuals clinically diagnosed with idiopathic Parkinson disease but with SWEDD demonstrate early cognitive decline. The results also suggest that recently diagnosed patients with SWEDD may be at even greater risk for cognitive decline than patients with DaTscan-confirmed early-stage Parkinson disease. While patients with SWEDD likely represent a heterogeneous group of etiologies, our results highlight the need to monitor these patients' cognitive function over time.

Objectives: Patients with Parkinson's disease often experience significant decline in verbal fluency over time; however, deep brain stimulation of the subthalamic nucleus (STN-DBS) is also associated with post-surgical declines in verbal fluency. The purpose of this study was to determine if Parkinson's patients who have undergone bilateral STN-DBS have greater impairment in verbal fluency compared to Parkinson's patients treated by medication only., Methods: A literature search yielded over 140 articles and 10 articles met inclusion criteria. A total of 439 patients with Parkinson's disease who underwent bilateral STN-DBS and 392 non-surgical patients were included. Cohen's d, a measure of effect size, was calculated using a random effects model to compare post-treatment verbal fluency in patients with Parkinson's disease who underwent STN-DBS versus those in the non-surgical comparison group., Results: The random effects model demonstrated a medium effect size for letter fluency (d=-0.47) and a small effect size for category fluency (d=-0.31), indicating individuals with bilateral STN-DBS had significantly worse verbal fluency performance than the non-surgical comparison group., Conclusions: Individuals with Parkinson's disease who have undergone bilateral STN-DBS experience greater deficits in letter and category verbal fluency compared to a non-surgical group.