Lee E. Neilson

Objective: To describe development of the Portland Suspected Environmental Exposures Questionnaire (SEEQ) and its initial application for environmental exposome profiling in isolated REM sleep behavior disorder (iRBD). Background: Environmental exposures may contribute to Parkinson disease and related synucleinopathies, yet existing instruments variably capture specific agents, co-exposures, exposure uncertainty, timing, and mitigating factors. Methods: SEEQ was iteratively developed to assess pesticides, solvents/industrial chemicals, welding fumes, heavy metals, residential and occupational exposures, and relevant lifestyle factors. Direct exposures were classified as definite, probable, possible, or uncertain/unlikely, with additional assessment of frequency/duration, life stage, and protective-equipment use. SEEQ was administered to participants with polysomnography-confirmed iRBD. Exposure prevalence, co-exposure patterns, and exploratory associations with clinical phenotypes and longitudinal progression were examined. Results: Eighty-three participants completed SEEQ; 81 (97.6%) completed all four direct exposure domains. Definite/probable exposure was reported for pesticides in 38.6%, solvents/industrial chemicals in 43.4%, welding fumes in 21.0%, and heavy metals in 34.1%. Among complete responders, 60.5% reported ≥1 and 42.0% ≥2 direct exposure domains. Forty-five participants identified ≥1 named agent or mixture. Greater exposure burden was cross-sectionally associated most consistently with greater autonomic symptom burden, but was not associated with longitudinal clinical worsening. Conclusion: SEEQ provides a practical, multidomain framework for structured environmental exposome profiling in prodromal synucleinopathy. Larger studies with external exposure validation and longitudinal follow-up are needed.

Background and ObjectivesClinical trials in REM sleep behavior disorder (RBD) to delay or prevent the development of Parkinson disease (PD), dementia with Lewy bodies (DLBs), and multiple system at...

Introduction: Parkinson’s disease is a neurodegenerative disease affecting motor and cognitive function that has a major impact on society. Epidemiological evidence has suggested that the incidence of PD may be increasing; however, the underlying etiology is unclear. Here, we investigated the role of increasingly used antipsychotics in the diagnosis of PD. Methods: We harnessed Merative insurance claims databases to conduct a case-control study of 65,275 new cases of PD and 652,364 age-, sex-, and time-matched controls. We estimated associations between exposure and duration of use for antipsychotics adjusted for important confounders using fixed effects logistic regression. We performed sensitivity analyses stratified by the level of D2 receptor inhibition to assess dose-response relationships; a lagged exposure analysis to address confounding by indication; analysis assessing exposure of other psychiatric medications without significant D2 inhibition (bupropion, trazodone, and Z-drugs); analysis assessing exposure of non-psychiatric medications with significant (metoclopramide) or no D2 inhibition (ondansetron). Results: We found cases with PD had elevated odds of antipsychotic exposure. Longer durations of exposure and greater affinity for the D2 receptor were associated with greater associations with PD. There was a dose-response relationship between D2 inhibition activity and increased odds of PD for a similar duration of exposure. There was a dose response relationship between duration of metoclopramide and the odds of PD; however, there was no such relationship between the non-D2 inhibiting control medications. The association between exposure to an antipsychotic and increased odds of PD was present even when the first exposure was 10 years prior to the PD diagnosis date. Conclusion: If these results are causal, antipsychotic use may explain up to 2.4% of all cases of PD. Given the increasing rate of use of these medications, and the concurrent increasing age-adjusted incidence of PD, there is an urgent need for further investigation into this association and greater awareness of the potential risks of these medications in older adults.

Background: Acute ischemic stroke (AIS) in those with Parkinson's disease (PD) is a growing healthcare burden but mortality studies are significantly lacking. Objective: To map short‐ and long‐term survival, stratified by relevant comorbidities and stroke characteristics. Methods: Individuals from the United States Veterans Health Administration were included. AIS and PD were defined by validated International Classification of Diseases (ICD) codes, pharmacy data, and encounter type. Covariates included demographics, smoking status, cardiovascular comorbidities, post‐traumatic stress disorder, traumatic brain injury, and frailty. Individuals with PD and stroke were matched 4:1 to controls and survival was measured over 10 years. Two percent of strokes were manually reviewed for size, location, and mechanism per TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Results: A total of 3173 cases of PD and AIS were identified and matched to groups of PD‐only, stroke‐only, and controls (N = 12,692 each). Survival analysis showed PD‐only and stroke‐only had a predictable increased mortality (added deaths ranged from 1.9 [0.9, 2.9] to 4.7 [2.9, 6.6] per 100 person‐years). PD + stroke showed further increased mortality with distinct timelines at 0–1‐, 1–5‐, and 5–10‐year periods and synergy accounted for 2.9 [0.5, 5.4] to 19.3 [14.0, 24.6] additional deaths across 10 years. Effects persisted after matching for cardiovascular comorbidities, neurotrauma, and frailty. PD + stroke compared with stroke‐only had smaller strokes (80.0% vs. 63.2%) and no differences in location, mechanism, or recurrence rates. Conclusions: Patients with PD and AIS had greater than expected mortality that was independent of comorbidities or stroke characteristics. This may reflect widespread structural and functional deficits that may warrant a targeted therapeutic strategy. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a usually prodromal manifestation of neurodegenerative disorders with α-synuclein pathology: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Clinical trials in the iRBD population face substantial barriers: limited access to well-characterized cohorts, inconsistent assessment protocols across centers, and the absence of validated biomarkers of disease burden. The North American Prodromal Synucleinopathy (NAPS) Consortium was established to address these challenges and facilitate clinical trials for neuroprotective therapies targeting synucleinopathy at the earliest known stages. In this multi-site, longitudinal, observational study, nine academic centers across North America will enroll and follow over 500 individuals with iRBD from existing sleep centers. Sixty control participants, matched for age, sex, and race will also be recruited. A harmonized protocol—including a standardized clinical battery assessing motor, cognitive, autonomic, psychiatric, sensory, and sleep function; structured diagnostic adjudication; biospecimen collection; and centralized analysis of both polysomnography and neuroimaging data—is outlined herein and reflects NAPS Stage 2. Each participants completes these assessments annually, and are replaced in the event of phenoconversion. By unifying assessments and expanding geographic reach, NAPS lays the groundwork for efficient, well-powered clinical trials designed to delay or prevent progression of iRBD to overt PD, DLB, or MSA—ultimately enabling earlier, more effective therapeutic intervention for neurodegenerative disease. Registered at clinicaltrials.gov (NCT05826457).

Thermoregulatory dysfunction—temperature intolerance and/or inappropriate compensation—is an underrecognized feature of Parkinson’s disease (PD) and is linked to poor quality of life. Multiple mechanisms may underlie this dysfunction, including α-synuclein deposition in relevant structures, altered functional connectivity in thermoregulatory networks, and disrupted neurotransmitter modulation, on top of the deleterious consequences of aging. Although multiple advanced tests can confirm this dysfunction, diagnosis is largely based on a detailed history. Once this critical symptom is identified, management focuses on crisis prevention and safety, as PD-specific clinical trials are often lacking. This narrative review of the literature addresses mechanisms, clinical expression, diagnostic evaluation, and management of thermoregulatory dysfunction in PD to help guide care for this underappreciated, yet potentially debilitating, non-motor symptom of PD. Future PD-specific trials are needed to further clarify underlying mechanisms and improve treatment options.

Variability in Pull Test Performance Within a Tertiary Movement Disorders Center