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IntroductionStatins were proposed to be neuroprotective; however, the effects are unknown in progressive supranuclear palsy (PSP), a pure tauopathy.MethodsData of 284 PSP cases and 284 age-matched, sex-matched, and race-matched controls were obtained from the environmental and genetic PSP (ENGENE-PSP) study. Cases were evaluated with the PSP Rating Scale, Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, and Neuropsychiatric Inventory. Statin associations with PSP risk, onset age, and disease features were analyzed.ResultsUnivariate models showed lower PSP risk for type 1 statin users (simvastatin, lovastatin, pravastatin). After adjusting for confounding variables, statin use and lower PSP risk association remained only at a trend level. For PSP cases, type 1 statins were associated with 1-year older onset age; type 2 statins (atorvastatin, rosuvastatin) were associated with the lower PSP Rating Scale and Unified Parkinson's Disease Rating Scale.ConclusionStatins may have inverse associations with PSP risk and motor impairment. Randomized prospective studies are required to confirm this effect. © 2020 International Parkinson and Movement Disorder Society.

OBJECTIVE:To study and provide an update on the state of clinical research in neurology in the United States. METHODS:US American Academy of Neurology members and chairs of departments of neurology were surveyed regarding clinical research in 2016. NIH data on the neuroscience pipeline and extramural grant funding were also collected. RESULTS:The response rate was 32% (n = 254) for nonchair researchers and 58% (n = 67) for department chairs. Researcher respondents were on average 50 years old, 66% were men, and 81% were actively conducting clinical research, with phase II/III clinical trials and outcome measure studies being the most common type of research conducted. Time to conduct research, recruitment, and administrative burden were the major barriers reported. According to department chairs, funding and training opportunities in patient-oriented research have increased over the last 10 years. Overall, applicants to neuroscience-specific NIH institutes for extramural funding have decreased over the same time period. CONCLUSIONS:The state of clinical research in neurology has remained relatively stable over the last 10 years, but neurologists still have barriers in conducting clinical research. There has been an interval decrease in neuroscience applicants for NIH funding, which raises concerns about the pipeline and future of clinical research in neurology. These results will serve as a reference for the development of solutions to these issues.

BackgroundCognitive dysfunction is common in progressive supranuclear palsy, but the influence of genetics on cognition in this disorder has not been well studied. The objective of this study was to investigate the effect of genes previously identified as risk alleles, including microtubule-associated protein tau, myelin-associated oligodendrocyte basic protein, eukaryotic translation initiation factor 2-alpha kinase 3, and syntaxin 6, as well as apolipoprotein E, on cognitive function in progressive supranuclear palsy.MethodsThe sample was composed of 305 participants who met criteria for possible or probable progressive supranuclear palsy. Genetic information was determined by TaqMan genotyping assays. A neuropsychological battery was administered to all study participants. Measures included in the battery evaluated for general cognition, executive function, memory, attention, language, and visuospatial ability.ResultsCognition did not vary significantly between individuals homozygous or heterozygous for the microtubule-associated protein tau H1 haplotype. However, cognition varied significantly at the subhaplotype level, with carriers of the microtubule-associated protein tau rs242557/A allele, which marks the H1c subhaplotype, performing better than noncarriers on measures of general cognitive function, executive function, and attention. No associations were found for other genes.ConclusionsThe results of the current study indicate that variations in microtubule-associated protein tau influence cognition in progressive supranuclear palsy. Although the H1c-specific rs242557/A allele is a risk factor for progressive supranuclear palsy, carriers of this allele may exhibit better cognition than non-carriers in patients with the atypical parkinsonian syndrome. Further studies are needed. © 2017 International Parkinson and Movement Disorder Society.

IntroductionThe pathophysiology of both PD and PSP is characterized by a pro-oxidant state. Uric acid is an oxidative stress marker. High uric acid blood levels have been associated with a reduced risk of PD and a decreased rate of disease progression. We investigated whether a low serum concentration of uric acid is also associated with PSP.MethodsWe measured serum uric acid concentrations in a subsample of the ENGENE PSP Cohort that included 75 cases and 75 frequency-matched-by-sex healthy controls (69 spouses, 6 in-laws) from four centers willing to participate (Case Western, Rush University, University of Utah, and University of Louisville). Case severity was characterized using the total PSP-Rating Scale, UPDRS, and Mattis Dementia Rating Scale. Unconditional logistic regression, Pearson's chi-squared test, and analysis of variance were used, as appropriate.ResultsThe mean uric acid level among cases (4.0 mg/dL) was not significantly lower than that of controls (4.1 mg/dL). When controlling for sex, there were no between-group statistical differences in uric acid levels. Uric acid levels were not correlated with disease severity.ConclusionsThe results of this study do not provide evidence of uric acid having a protective role in PSP, even if oxidative injury is important in the pathophysiology of this disorder. The lack of statistical significance suggests that there is no direct association between uric acid levels and PSP. However, a small inverse association cannot be excluded. © 2016 Movement Disorder Society.

Background: The Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) was designed to be more sensitive to mild motor severity than the Unified Parkinson's Disease Rating Scale (UPDRS). Objective: To test whether MDS‐UPDRS Part III items provide increased sensitivity to mild motor severity when compared to the same items of the UPDRS in de novo PD patients. Method: Using a sample of 129 de novo PD patients assessed at one time point simultaneously with both scales, we compared the scale's scores on the 17 items measuring the same motor function. The scaling anchors for the MDS‐UPDRS were Slight, Mild, Moderate and Severe, and for the UPDRS were Mild, Moderate, Severe and Marked. Using Classical Test Theory (CTT) we compared the distributions of the scaling anchors from the individual items. Using Item Response Theory (IRT), we examined the sensitivity of the scaling anchors from each scale to the latent‐trait measurement of overall parkinsonian motor severity. Results: There was 2193 observations of individual scaling anchors from the 17 items in both scales. The CTT approach revealed frequent floor effects with only the item assessing Gait demonstrating a significance difference in the scaling distribution between the scales (P = 0.005). The IRT analyses revealed similar levels of sensitivity to the latent trait of PD motor function. Conclusion: These results do not support increased sensitivity of MDS‐UPDRS over the UPDRS for assessing mild motor severity in de novo PD patients, with significant difference in the scaling only for the item assessing gait. [ABSTRACT FROM AUTHOR]

Objectives: Palliative care addresses the suffering of patients and families affected by progressive illness through the management of medical symptoms, psychosocial issues, and spiritual concerns. Although there is an emerging interest in applying palliative care to Parkinson's disease (PD), potential palliative care needs have not been systematically investigated in PD patients. Our primary objective was to determine the prevalence of clinically significant symptomatic, psychosocial, and spiritual issues in PD and understand their impact on health‐related quality of life (HRQOL). Secondary objectives included comparing the level of palliative care needs of PD patients to advanced cancer patients and assessing preferences for advance care planning. Methods: Ninety PD patients and 47 patients with advanced cancer were surveyed regarding potential palliative care needs, including symptom burden, mood, anticipatory grief, and spiritual well‐being. PD patients completed additional scales regarding HRQOL, motor symptoms, cognitive impairment, and preferences regarding advance care planning. Results: Potential palliative care needs, including high symptom burden and grief, were common in PD patients and contributed to HRQOL even when controlling for depression and motor severity. In all domains investigated, PD patients had similar or higher levels of palliative care needs as patients with advanced cancer. PD patients expressed a desire to complete advance directives early in the disease course and with a physician. Conclusions: Palliative care needs contribute to HRQOL in PD and are of similar severity as cancer patients. This study supports and helps focus efforts to integrate palliative care principles in PD care across the spectrum of the disease. [ABSTRACT FROM AUTHOR]

Prolonged continuous performance of a cognitively demanding task induces cognitive fatigue and is associated with a time-related deterioration of objective performance, the degree of which is referred to cognitive fatigability. Although the neural underpinnings of cognitive fatigue are poorly understood, prior studies report changes in neural activity consistent with deterioration of task-related networks over time. While compensatory brain activity is reported to maintain motor task performance in the face of motor fatigue and cognitive performance in the face of other stressors (e.g., aging) and structural changes, there are no studies to date demonstrating compensatory activity for cognitive fatigue. High-density electroencephalography was recorded from human subjects during a 160 min continuous performance of a cognitive control task. While most time-varying neural activity showed a linear decline over time, we identified an evoked potential over the anterior frontal region which demonstrated an inverted U-shaped time-on-task profile. This evoked brain activity peaked between 60 and 100 min into the task and was positively associated with better behavioral performance only during this interval. Following the peak and during subsequent decline of this anterior frontal activity, the rate of performance decline also accelerated. These findings demonstrate that this anterior frontal brain activity, which is not part of the primary task-related activity at baseline, is recruited to compensate for fatigue-induced impairments in the primary task-related network, and that this compensation terminates as cognitive fatigue further progresses. These findings may be relevant to understanding individual differences in cognitive fatigability and developing interventions for clinical conditions afflicted by fatigue. [ABSTRACT FROM AUTHOR]

Background Parkinson's disease ( PD) dementia ( PDD) is a major cause of morbidity and mortality in PD, which severely affects patient functioning and quality of life and increases the risk for nursing home admission. Unfortunately, current treatment options for PDD are limited and have only marginal therapeutic effects. As novel treatments are developed, there will be a need to assess their efficacy in well-designed, randomized, controlled trials. However, there is no consensus on the optimal outcome measures for use in PDD clinical trials. Methods A systematic review of PDD clinical trials and empirical studies of outcome measures used in PDD was performed. Outcome measures were divided into 5 categories: (1) cognitive; (2) behavioral and mood; (3) activities of daily living and quality of life; (4) global; and (5) caregiver burden. Findings A total of 20 PDD pharmacological clinical trials were identified. These trials incorporated a broad array of outcome measures, which were used inconsistently across trials. We summarize the psychometric properties and other relevant data on outcome measures used, including their diagnostic utility, inter-rater reliability, test-retest reliability, responsiveness, clinically meaningful change, and availability of alternate forms. Conclusions We have identified the best-evidenced PDD outcome measures in each domain. Further research is needed to assess the validity, reliability, and clinically meaningful change of these measures in PDD to inform the design of future clinical trials and enhance the ability of clinicians, researchers, and policy makers to interpret study results. In addition, the development of outcome measures specific to PDD may be warranted. [ABSTRACT FROM AUTHOR]

Background. People with Parkinson disease (PD) typically have complaints of weakness. The mechanisms underlying this deficit have not been well established, although many factors may contribute. Objective. This investigation aimed to characterize quadriceps muscle weakness and activation failure in people with PD and explore whether these deficits were related to disease severity. The authors further sought to examine quadriceps muscle fatigability. Methods. This was a cross-sectional comparison of 17 people with mild-severe PD and 17 healthy adults matched by age, sex, and body mass index (BMI). The Unified Parkinson’s Disease Rating Scale motor score (UPDRS motor) ranged from 9.5 to 61.0. Participants were divided into those with low-PD motor signs (UPDRS motor < 31.7) and high-PD motor signs (UPDRS motor ≥ 31.7). Measures of quadriceps performance included isometric torque, central activation using doublet interpolation, and an isokinetic fatigue test. Results. Participants with high-PD motor signs had significantly more quadriceps weakness and central activation deficits than those with low-PD motor signs or healthy controls. Strength and activation deficits correlated strongly with UPDRS motor score. Quadriceps muscle fatigue was present in healthy controls and in those with low-PD motor signs but not in those with high-PD motor signs. Conclusions. These findings provide additional evidence for lower-extremity strength loss with PD; central activation deficits may account for some of the strength deficits, especially with increased PD motor signs. Also, muscle fatigue did not occur in individuals with a greater degree of PD motor signs, most likely because of insufficient central activation to allow for muscle overload to induce metabolic fatigue. [ABSTRACT FROM PUBLISHER]