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In our efforts to create more public awareness about Parkinson’s disease, we often emphasize the tremendous impact of this common disease on an individual’s life. However, in public awareness campaigns, we largely avoid discussions on the survival of people with Parkinson’s disease (PwP). Many clinicians even state that the survival with Parkinson’s disease is close to normal. In this article, we contemplate on findings regarding the mortality of Parkinson’s disease in order to spark a discussion about what information we should provide to affected individuals and their near ones about the life expectancy of PwP. Our narrative review of the evidence indicates that although the survival of PwP has improved over time, PwP still live fewer years than their age- and sex-matched population comparators, albeit at older ages this difference can be small. We feel that it is important to emphasize this information towards PwP, the general public, policymakers and funding bodies. We hope that this will help to create a better understanding of the enormous impact that this disorder can have on affected individuals, even beyond the disability that is experienced during life.

Objective: With Huntington disease (HD), a fatal neurodegenerative disease where the prevalence of suicidal thoughts and behavior (STB) remains elevated as compared to other neurological disorders, it is unknown whether STB and health-related quality of life (HRQoL) affect plans for the end of life or more broadly, advance care planning (ACP). Conversely, it is unknown whether ACP would provoke future changes to STB and HRQoL. Therefore, we sought to evaluate whether STB and HRQoL patient-reported outcomes (PROs) contribute to ACP and whether ACP relates to changes in STB and HRQoL at 24 months. Methods: HD-validated clinician- and patient-assessments (i.e., HRQoL PROs) were obtained at baseline enrollment, 12 and 24 months through our multi-center study (HDQLIFE?) throughout the United States among people with premanifest, early-stage, and late-stage manifest HD. We used linear mixed-effects models to determine the relationships between STB and HRQoL at baseline and HDQLIFE End of Life Planning at follow-up. Separate linear mixed-effects models were used to assess the relationship between HDQLIFE End of Life Planning at baseline, and HRQoL and STB at 12 and 24 months. False discovery rate adjustments were used to account for multiple comparisons. Results: At baseline enrollment, STB and HRQoL were not related to HDQLIFE End of Life Planning at 12 or 24 months. Similarly, at baseline, HDQLIFE End of Life Planning demonstrated no association with STB or HRQoL at 12 or 24 months. Interpretation: STB and HRQoL PROs do not significantly affect patient engagement with ACP. Most importantly, engaging in ACP does not cause untoward effects on HRQoL or STB for this rare neurodegenerative disease where the lifetime prevalence of STB approaches 30%.

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.

Abstract Graph theory-based approaches are efficient tools for detecting clustering and group-wise differences in high-dimensional data across a wide range of fields, such as gene expression analysis and neural connectivity. Here, we examine data from a cross-sectional, resting-state magnetoencephalography study of 89 Parkinson’s disease patients, and use minimum-spanning tree (MST) methods to relate severity of Parkinsonian cognitive impairment to neural connectivity changes. In particular, we implement the two-sample multivariate-runs test of Friedman and Rafsky (Ann Stat 7(4):697–717, 1979) and find it to be a powerful paradigm for distinguishing highly significant deviations from the null distribution in high-dimensional data. We also generalize this test for use with greater than two classes, and show its ability to localize significance to particular sub-classes. We observe multiple indications of altered connectivity in Parkinsonian dementia that may be of future use in diagnosis and prediction.

Abstract Objective Previous work in Huntington’s disease (HD) has shown that a sense of meaning and purpose (M&P) is positively associated with positive affect and well‐being (PAW); however, it was unknown whether HD‐validated patient‐reported outcomes (PROs) influence this association and how M&P impacts PROs in the future. Our study was designed to examine if HD‐validated PROs moderate the relationship between M&P and PAW and to evaluate if baseline M&P predicts 12‐ and 24‐month changes in HD‐validated PROs. Methods This was a longitudinal, multicenter study to develop several PROs (e.g., specific for the physical, emotional, cognitive, and social domains) for people with HD (HDQLIFE). The sample consisted of 322 people with HD (n = 50 prodromal, n = 171 early‐stage manifest, and n = 101 late‐stage manifest HD). A single, multivariate linear mixed‐effects model was performed with PAW as the outcome predicted by main effects for M&P and several moderators (i.e., an HD‐validated PRO) and interactions between M&P and a given PRO. Linear‐mixed models were also used to assess if baseline M&P predicted HD‐validated PROs at 12 and 24 months. Results Higher M&P was positively associated with higher PAW regardless of the magnitude of symptom burden, as represented by HD‐validated PROs, and independent of disease stage. In our primary analysis, baseline M&P predicted increased PAW and decreased depression, anxiety, anger, emotional/behavioral disruptions, and cognitive decline at 12 and 24 months across all disease stages. Interpretation These findings parallel those seen in the oncology population and have implications for adapting and developing psychotherapeutic and palliative HD interventions.

Abstract Symptomatic management of Parkinson’s disease (PD) is complex and many symptoms, especially non-motor symptoms, are not effectively addressed with current medications. In the US, cannabis has become more widely available for medical and recreational use, permitting those in the PD community to try alternative means of symptom control. However, little is known about the attitudes towards, and experiences with, cannabis use among those living with PD. To address this shortcoming, we distributed an anonymous survey to 7,607 people with PD in January 2020 and received 1339 responses (17.6%). 1064 complete responses were available for analysis. Respondents represented 49 states with a mean age of 71.2 years (±8.3) and mean PD duration of 7.4 years (±6.2). About a quarter of respondents (24.5%) reported cannabis use within the previous six months. Age and gender were found to be predictors of cannabis use in this sample (Age OR = 0.95, 95% CI 0.93 to 0.97; Male OR = 1.44, 95% CI 1.03 to 2.03). Users reported learning about cannabis use from the internet/news (30.5%) and friends or other people with PD (26.0%). Cannabis users were more likely to report insufficient control of their non-motor symptoms with prescription medications than non-users (p = 0.03). Cannabis was primarily used for PD (63.6%) and was most often used to treat nonmotor symptoms of anxiety (45.5%), pain (44.0%), and sleep disorders (44.0%). However, nearly a quarter of users (23.0%) also reported they had stopped cannabis use in the previous six months, primarily due to a lack of symptom improvement (35.5%). Three quarters of respondents (75.5%) did not use cannabis, primarily because there was a lack of scientific evidence supporting efficacy (59.9%). Our results suggest that the lack of formal guidance or research evidence about cannabis for PD may in part underlie inconsistencies in both use and reported effectiveness.

IntroductionCognitive impairment is a highly prevalent non-motor feature of Parkinson’s disease (PD). A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex (PFC), a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD.MethodsProton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD (CTL), as well as PD participants with either normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD). Ratios to Creatine (Cre) resonance were obtained for glutamate (Glu), glutamine and glutamate combined (Glx), N-acetylaspartate (NAA), myoinositol (mI), and total choline (Cho), and correlated with cognitive scores across multiple domains (executive function, learning and memory, language, attention, visuospatial function, and global cognition) administered to the PD participants only.ResultsWhen individuals retain cognitive capabilities, the presence of Parkinson’s disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction.ConclusionThese preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups.

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.

Caregiver burden is a term that refers to the adverse effect of caregiving on the physical, emotional, social, spiritual, and financial well-being of the caregiver. Caregiver burden is associated with providing care to an individual with a chronic illness or disability, and the unique symptoms of Parkinson disease (PD) can amplify a patient's needs and reliance on others, leading to adverse outcomes for patients and their caregivers. In this scoping review of the literature from January 2017 through April 2022 that included 114 studies, we provide an updated, evidence-based summary of patient and caregiver-related factors that contribute to caregiver burden in PD. We also describe the impact of caregiver stress and burden on caregivers based on qualitative research studies and review recent interventions to mitigate burden. By providing clinical updates for practitioners, this review is designed to improve recognition of caregiver burden in the post-pandemic era and foster the development of targeted interventions to reduce caregiver burden in PD. [ABSTRACT FROM AUTHOR]

Introduction: Dysphagia causing aspiration pneumonia is a common complication in the advanced stages of neurodegenerative disorders. Historically, physicians attempted to prevent this complication with gastrostomy tube (GT) placement. Its use is supported in amyotrophic lateral sclerosis (ALS), not supported in Alzheimer’s disease (AD), and without disease-specific guidelines in Parkinson’s disease (PD). Method: The rate of GT placement in these three populations over two decades, from 1990 to 2010, was calculated using a binomial regression model with the data extracted using diagnosis and procedural codes from a national database. The median length-of-stay (LOS) and discharge destinations were compared. Results: The rate of GT placement was 6.0% lower annually in AD, 3.4% in PD, and 0.2% in ALS (all p ≤ 0.007). The analysis of hospital LOS and discharge destination showed 3.2 to 5.5 days longer LOS with GT placement in all groups (all p ≤ 0.01), and three to four times lower odds of going home with GT placement in AD and PD groups (OR 0.28, 95% CI 0.14–0.55, and OR 0.22, CI 0.11–0.42 respectively), while unchanged in ALS group (OR 1.1, 95% CI 0.6–1.9). Conclusion: Despite the downward trend of GT placement over two decades, thousands of AD and PD patients still underwent GT placement annually, and this was associated with longer LOS in all groups and increased likelihood of being discharged to a nursing facility in AD and PD. Further research is necessary to understand the effects of GT on physician practices and patient expectations in advanced AD and PD.