2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:Td94,M.G. has received research grants from the King Baudouin Foundation, ERN-RND, KU Leuven internal funds and The Michael J. Fox Foundation outside the submitted work. J.N. is supported by ZonMW, The Michael J. Fox Foundation, Gossweiler Foundation and ERN-RND outside the submitted work, and he is a member of the scientific adviser board of Cue2Walk. S.A.F. receives honoraria from Biogen, Takeda and Neurocrine; he receives grants from Sun Pharmaceuticals Advanced Research Company, Aspen, Biohaven, Neurocrine, Rho Inc, CHDI Foundation, The Michael J. Fox Foundation, the National Institutes of Health (NIH) 1 P50 NS123103-01, NIH 1R01NS125294-01 and Parkinson Foundation; he receives royalties from Demos, Blackwell Futura, Springer for textbooks, and Uptodate; he acts as consultant for Signant Health. B.R.B. serves as co-Editor-in-Chief for the Journal of Parkinson ’ s Disease , serves on the editorial board of Practical Neurology and Digital Biomarkers , has received fees from serving on the scientific advisory board for the Critical Path Institute, Gyenno Science, MedRhythms, UCB, Kyowa Kirin and Zambon (paid to the Institute), has received fees for speaking at conferences from AbbVie, Bial, Biogen, GE Healthcare, Oruen, Roche, UCB and Zambon (paid to the Institute), and has received research support from Biogen, Cure Parkinson’s, Davis Phinney Foundation, Edmond J. Safra Foundation, Fred Foundation, Gatsby Foundation, Hersenstichting Nederland, Horizon 2020, IRLAB Therapeutics, Maag Lever Darm Stichting, The Michael J. Fox Foundation, Ministry of Agriculture, Ministry of Economic Affairs and Climate Policy, Ministry of Health, Welfare and Sport, Netherlands Organization for Scientific Research (ZonMw), Not Impossible, Parkinson Vereniging, Parkinson’s Foundation, Parkinson’s UK, Stichting Alkemade-Keuls, Stichting Parkinson NL, Stichting Woelse Waard, Topsector Life Sciences and Health, UCB, Verily Life Sciences, Roche and Zambon. A.N. is supported by The Michael J. Fox Foundation. F.B.H. is supported by NIH, Department of Defence and The Michael J. Fox Foundation. E.C. acts as a scientific adviser for Abbvie, Esteve and Bial. D.Z. is currently employed by Cue2Walk International B.V. (The Hague, The Netherlands). T.V. has no disclosures related to this work; he has received support from the NIH/National Center for Advancing Translational Sciences (UM1TR004909, UL1TR003107), Parkinson’ Foundation (PF-JFA-1935), NSF/DART (23-EPS4-0028), NIH/National Cancer Institute (U24 3U24CA215109-02S1), and salary support from the University of Arkansas for Medical Sciences. A.F. has no disclosures related to this work; he has stock ownership in Inbrain Pharma and has received payments as consultant and/or speaker from Abbvie, Abbott, AskBio, Boston Scientific, Ceregate, Dompé Farmaceutici, Inbrain Neuroelectronics, Ipsen, Medtronic, Iota, Syneos Health, Merz, Sunovion, Paladin Labs, UCB and Sunovion; he has received research support from Abbvie, Boston Scientific, Medtronic, Praxis, ES and receives royalties from Springer. J.M.H. received grant support from The Michael J Fox Foundation, the NIH and the Israel Ministry of Health. S.J.G.L. is supported by an NHMRC Leadership Fellowship (no. 1195830). All other authors declare no competing interests.31:T7f9,Obstructive sleep apnea (OSA) is associated with many health conditions, including dementia and early mortality. Prior epidemiological studies linking OSA with Parkinson disease (PD) are conflicting, and no studies have examined the influence of continuous positive airway pressure (CPAP), the criterion standard treatment for OSA, on PD risk. To examine the association between OSA with incident Parkinson disease among US veterans and risk modification by CPAP. This electronic health record (EHR)-based cohort study was conducted among US veterans from January 1, 1999, to December 30, 2022, with mean (SD) follow-up of 4.9 (1.8) years. Veterans with PD at the time of exposure or incomplete records were excluded. Data analysis was completed from September 2024 to September 2025. OSA was defined by its appropriate administrative code; CPAP usage was extracted from a semistructured medical interview field in the EHR. The primary outcome, cumulative incidence of PD, was calculated adjusting for competing risk of death after balancing for age, race, sex, and smoking status. A total of 13 737 081 US veterans were screened, and 11 310 411 veterans (1 109 543 female veterans [9.8%]) with mean (SD) age of 60.5 (14.7) years were included in analyses. Of included veterans, 1 552 505 (13.7%) had OSA. Veterans with OSA demonstrated 1.61 additional cases of PD (point estimate; 95% CI, 1.13-2.09) at 6 years from diagnosis per 1000 people compared to those without OSA. Results were confirmed when adjusting for body mass index, vascular comorbidities, psychiatric conditions, and relevant medications and were of greater magnitude in female veterans. Case numbers were significantly reduced when treated with CPAP early in the disease course. In this EHR-based cohort study, OSA appeared to be an independent risk factor for the later development of PD and could be modified by early treatment with CPAP. Effective screening measures and protocols for consistent adherence to CPAP may have large impacts on brain health.32:Tcce, Importance Obstructive sleep apnea (OSA) is associated with many health conditions, including dementia and early mortality. Prior epidemiological studies linking OSA with Parkinson disease (PD) are conflicting, and no studies have examined the influence of continuous positive airway pressure (CPAP), the criterion standard treatment for OSA, on PD risk. Objective To examine the association between OSA with incident Parkinson disease among US veterans and risk modification by CPAP. Design, Setting, and Participants This electronic health record (EHR)–based cohort study was conducted among US veterans from January 1, 1999, to December 30, 2022, with mean (SD) follow-up of 4.9 (1.8) years. Veterans with PD at the time of exposure or incomplete records were excluded. Data analysis was completed from September 2024 to September 2025. Exposure OSA was defined by its appropriate administrative code; CPAP usage was extracted from a semistructured medical interview field in the EHR. Main Outcomes and Measures The primary outcome, cumulative incidence of PD, was calculated adjusting for competing risk of death after balancing for age, race, sex, and smoking status. Results A total of 13 737 081 US veterans were screened, and 11 310 411 veterans (1 109 543 female veterans [9.8%]) with mean (SD) age of 60.5 (14.7) years were included in analyses. Of included veterans, 1 552 505 (13.7%) had OSA. Veterans with OSA demonstrated 1.61 additional cases of PD (point estimate; 95% CI, 1.13-2.09) at 6 years from diagnosis per 1000 people compared to those without OSA. Results were confirmed when adjusting for body mass index, vascular comorbidities, psychiatric conditions, and relevant medications and were of greater magnitude in female veterans. Case numbers were significantly reduced when treated with CPAP early in the disease course. Conclusions and Relevance In this EHR-based cohort study, OSA appeared to be an independent risk factor for the later development of PD and could be modified by early treatment with CPAP. Effective screening measures and protocols for consistent adherence to CPAP may have large impacts on brain health. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Parkinson Disease: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Parkinson Disease (condition). Clinician-written summaries and actionable practice insights. 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Summaries and tags are based solely on the title and cannot reflect actual study findings, design, or sample size.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3048","tag_type":"warning","value":"Study design, level of evidence, sample size, sex, and age group tags could not be assigned without access to the paper content.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated whether exhaled carbon monoxide (CO) levels are associated with the etiology or pathophysiology of Parkinson disease (PD).","limitations":"The paper metadata provided does not include full text, so specific findings, sample sizes, and quantitative results cannot be extracted or verified."}},{"doi":"10.1001/jamaneurol.2026.3037","pmid":"42709430","title":"Smoking, Exhaled Carbon Monoxide, and Risk of Parkinson Disease","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-09-08T00:00:00.000Z","url":"https://doi.org/10.1001/jamaneurol.2026.3037","source_score":138,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-13T06:21:44.518Z","updated_at":"2026-09-13T06:21:44.518Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"condition","value":"Neurodegenerative Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"generic","value":"carbon monoxide","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"modality","value":"Carbon Monoxide Exposure","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"sample_size","value":"n=512701","value_numeric":512701},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"warning","value":"PD case counts are relatively low (n=1,131 overall; n=675 among never-smokers) relative to the cohort size, which may limit statistical precision at the extremes of CO exposure bands.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the mechanistic novelty (CO as the mediating agent) rather than a new treatment — clinicians should not interpret findings as recommending smoking or CO inhalation outside trial settings.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.3037","tag_type":"warning","value":"The study population is exclusively Chinese adults; generalizability to other ethnicities and environments is uncertain.","value_numeric":null}],"summaries":{"what_studied":"This nationwide prospective cohort study (China Kadoorie Biobank, n=512,701 adults aged 30–79) examined whether exhaled carbon monoxide (CO) levels — both from smoking and non-smoking sources — are associated with incident Parkinson disease (PD) risk over ~12 years of follow-up (2004–2019).","key_result":"Regular smoking was associated with lower PD risk (adjusted HR 0.70; 95% CI 0.62–0.79). Among never-smokers, higher exhaled CO showed a dose-dependent inverse association with PD: HRs ranged from 0.85 (2.0–<3.0 ppm) to 0.62 (3.0–<5.0 ppm) to 0.65 (≥11.5 ppm) vs. reference <2.0 ppm (P for trend <.001), with no corresponding signal for smoking-related diseases or other neurodegenerative diseases.","limitations":"- Observational design cannot establish causality; residual confounding (e.g., unaccounted CO sources such as solid fuel use) is possible despite adjustments.\n- PD ascertainment relied on linkage to death/disease registries and health insurance — clinical underdiagnosis in rural China could bias case counts.\n- Exhaled CO was measured only at baseline (single time point), limiting assessment of cumulative or changing exposure.","practice_takeaway":"CO itself — not just other tobacco constituents — may drive smoking's inverse association with PD, supporting the biological plausibility of ongoing CO-based clinical trials for PD. Clinicians should be aware that this does not endorse smoking, given its well-confirmed harms for lung cancer, heart disease, and stroke."}},{"doi":"10.1001/jamaneurol.2026.2998","pmid":"42709445","title":"Common\n MC1R\n Variants and Parkinson Disease Progression","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-09-08T00:00:00.000Z","url":"https://doi.org/10.1001/jamaneurol.2026.2998","source_score":41,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-13T06:21:44.144Z","updated_at":"2026-09-13T06:21:44.144Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"generic","value":"MC1R loss-of-function variants","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"modality","value":"Genetic Biomarker","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"sample_size","value":"n=1449","value_numeric":1449},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"study_design","value":"Longitudinal Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"warning","value":"Study is predominantly European-ancestry; findings should not be extrapolated to other populations without further research.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously—this is an observational study and MC1R genotyping is not yet standard clinical practice, but the high carrier frequency and replication make the findings clinically significant.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"warning","value":"The monogenic PD cohort (LRRK2, GBA carriers) showed no significant additive effect of MC1R LoF on top of GBA, only a trend for LRRK2; clinical implications differ by genetic background.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2998","tag_type":"warning","value":"The total sample size of 1,449 combines the PPMI cohort (n=809), replication cohort (n=587), and prodromal cohort (n=53); these are analyzed separately, not pooled. The prodromal phenoconversion result is based on only 53 participants and should be interpreted with caution.","value_numeric":null}],"summaries":{"what_studied":"This longitudinal cohort study (PPMI, July 2010–January 2026; replication via SURE-PD2/3 and STEADY-PD III, June 2009–June 2019) examined whether MC1R loss-of-function (LoF) variants—carried by >60% of Europeans—are associated with faster motor decline in 809 PPMI participants with PD (505 carriers, 304 noncarriers) and 587 replication participants, plus 53 prodromal participants, over up to 12 years.","key_result":"In sporadic PD (n=383), MC1R LoF carriers showed **30% faster motor decline** on MDS-UPDRS III OFF-state (β=0.57 points/year; 95% CI 0.16–0.98; P=.006); replication showed **50% faster decline** (β=1.37; 95% CI 0.28–2.46; P=.01). Prodromal MC1R LoF carriers had a **>4-fold higher risk** of phenoconversion to PD (SHR 4.75; 95% CI 1.48–15.27; P=.009). No significant differences were seen in non-motor outcomes, DAT-SPECT, or CSF biomarkers.","limitations":"- The prodromal phenoconversion analysis was very small (n=53; 34 carriers, 19 noncarriers), limiting precision.\n- The study population is predominantly of European descent, so findings may not generalize to other ancestries.\n- Survivorship bias in the replication cohort (faster progressors initiated treatment earlier and dropped out sooner) may underestimate true progression rates.","practice_takeaway":"MC1R LoF genotyping could help identify a large, common genetic subgroup of PD patients (>60% of Europeans) with faster motor progression, supporting its use in **prognostic counseling and clinical trial enrichment**. Clinicians should be aware that standard non-motor and biomarker measures may not differentiate these patients."}},{"doi":"10.1016/j.ajo.2026.08.048","pmid":"42702228","title":"Comment on, “Glaucoma and Neurodegenerative Disease Risk: A 10-Year Assessment of Real-World Global Data”","journal_title":"American Journal of Ophthalmology","journal_issn":"0002-9394","published_at":"2026-09-06T00:00:00.000Z","url":"https://doi.org/10.1016/j.ajo.2026.08.048","source_score":11,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-13T06:21:53.915Z","updated_at":"2026-09-14T06:23:13.662Z","tags":[{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"condition","value":"Glaucoma","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"condition","value":"Neurodegenerative Disease","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"condition","value":"Normal-Tension Glaucoma","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"condition","value":"Primary Open-Angle Glaucoma","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"study_design","value":"Editorial / Correspondence","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"study_design","value":"Letter / Commentary","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"warning","value":"No sample size is applicable to this paper itself — the index study by Wong et al. is referenced but its data are not reproduced here.","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"warning","value":"Only the paper metadata (title, DOI, journal, publication date) was provided — no abstract, methods, results, or conclusions were available. All summary fields are set to null as no clinical content could be extracted. Tags and suggested searches are inferred from the title only.","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"warning","value":"The mitochondrial dysfunction hypothesis proposed is speculative and explicitly framed by the authors as requiring future longitudinal validation.","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"warning","value":"This is a commentary/letter responding to a prior study; it does not present primary data of its own.","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.08.048","tag_type":"warning","value":"This is a correspondence/commentary with no original patient data; all clinical claims are derived from cited external studies.","value_numeric":null}],"summaries":{"what_studied":"This correspondence comments on a 10-year real-world observational study (Wong et al.) linking glaucoma subtypes to subsequent neurodegenerative disease risk, arguing that mitochondrial dysfunction deserves greater emphasis as a shared biological mechanism across glaucoma subtypes and related neurodegeneration.","key_result":"The authors highlight that normal-tension glaucoma (NTG) was the subtype most clearly linked to subsequent Parkinson disease in the index study, and propose mitochondrial dysfunction — including impaired oxidative phosphorylation, defective mitophagy, and mitochondrial DNA variants — as a plausible unifying mechanism connecting glaucoma to neurodegenerative conditions such as Parkinson disease and Alzheimer disease.","limitations":"This is a commentary with no original data; arguments are hypothesis-generating and based on secondary synthesis of cited studies. The proposed role of mitochondrial dysfunction as a shared susceptibility factor remains unproven and is difficult to test in large database cohorts.","practice_takeaway":"Clinicians managing glaucoma — especially NTG — should be aware of the emerging evidence linking mitochondrial dysfunction to both ocular and central neurodegeneration, though this does not yet change practice. Future studies integrating glaucoma phenotyping with mitochondrial function assessments may clarify whether shared biological pathways underlie these epidemiological associations."}},{"doi":"10.1001/jamaneurol.2026.2274","pmid":"42475105","title":"Environmental Risk in Parkinson Disease—Bring the Noise","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-07-20T00:00:00.000Z","url":"https://doi.org/10.1001/jamaneurol.2026.2274","source_score":25,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-26T13:44:32.832Z","updated_at":"2026-07-26T13:44:32.832Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.2274","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2274","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2274","tag_type":"study_design","value":"Commentary","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2274","tag_type":"warning","value":"Level of evidence and sample size cannot be determined from the available metadata alone.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2274","tag_type":"warning","value":"Only bibliographic metadata was provided — no abstract, body text, or results were included. Summaries, tags, and impact flags cannot be fully populated without the full paper content.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2274","tag_type":"warning","value":"Study design is inferred as 'Commentary' based on the title phrasing ('Bring the Noise') and publication context, but this is not confirmed by the source text.","value_numeric":null}],"summaries":{"what_studied":"This appears to be a commentary or perspective piece examining environmental risk factors — specifically noise exposure — in the development of Parkinson disease.","limitations":"The source text provides only the title, DOI, journal, and publication date — no abstract, methods, results, or conclusions are available for extraction."}},{"doi":"10.1001/jamaneurol.2026.2262","pmid":"42475104","title":"Road Traffic Noise, Noise Difference Between Residential Facades, and Risk of Parkinson Disease","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-07-20T00:00:00.000Z","url":"https://doi.org/10.1001/jamaneurol.2026.2262","source_score":357,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-25T13:57:38.391Z","updated_at":"2026-07-25T13:57:38.391Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"modality","value":"Environmental Noise Exposure","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"sample_size","value":"n=3103577","value_numeric":3103577},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"warning","value":"Full text was not accessible (publisher security block); summary is based solely on the abstract and results sections provided.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"warning","value":"Study population is exclusively Danish, which may limit generalizability to populations with different urban noise profiles or genetic backgrounds.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2262","tag_type":"warning","value":"The 'practice_changing' impact flag reflects a novel, large-scale finding linking road noise to PD risk — but effect sizes are modest (HR ~1.03–1.06) and causality is not established; clinical translation should be interpreted cautiously.","value_numeric":null}],"summaries":{"what_studied":"This Danish nationwide prospective cohort study (2000–2017) examined whether long-term residential road traffic noise exposure (10-year time-weighted LDEN at most- and least-exposed facades) was associated with incident Parkinson disease (PD) in adults aged 40+ (n=3,103,577), adjusting for air pollution, green space, and sociodemographics.","key_result":"20,587 participants developed PD. LDEN at the most exposed facade (LDEN-Max) was associated with HR 1.03 (95% CI, 1.00–1.05) per 11.5 dB IQR increment; accounting for facade noise difference (Δnoise) strengthened this to HR 1.06 (95% CI, 1.02–1.09). Having a quiet-side facade (Δnoise ≥10 dB) was linked to lower PD risk at noise levels above 50 dB.","limitations":"- Observational design prevents causal inference; residual confounding (e.g., unmeasured lifestyle factors) cannot be excluded despite adjustment for smoking and physical activity in a subpopulation only.\n- Noise exposure was modeled, not measured directly, potentially introducing exposure misclassification.\n- PD cases were identified via a national register, which may miss undiagnosed or primary-care-only cases.","practice_takeaway":"Long-term road traffic noise appears to modestly raise PD risk, and access to a quiet residential facade may attenuate this risk. Clinicians and urban planners should consider noise mitigation (e.g., quiet-side building design) as a potential neuroprotective strategy."}},{"doi":"10.1212/wnl.0000000000218296","pmid":"42447421","title":"Legal Protections to Mitigate Discrimination due to Neurodegenerative Biomarker Status","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-07-14T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218296","source_score":19,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-23T07:33:14.580Z","updated_at":"2026-08-23T07:33:14.580Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"modality","value":"Biomarker Testing","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"study_design","value":"Policy Analysis / Legal Review","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"warning","value":"No primary empirical data are presented; this is a legal/policy opinion piece, not a clinical study — sample size and statistical outcomes are not applicable.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"warning","value":"Study design label is non-standard; the article is a legal and policy analysis published in a clinical neurology journal, which may not map cleanly onto conventional evidence hierarchies.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"warning","value":"The 'impact_flag' of safety_signal is applied in the context of patient legal and privacy risk, not a pharmacologic or procedural safety signal in the traditional sense.","value_numeric":null}],"summaries":{"what_studied":"This policy analysis evaluates gaps in U.S. federal legal protections (GINA, ADA, ACA, HIPAA) for individuals undergoing neurodegenerative biomarker testing (AD, PD, ALS) — particularly those in preclinical or prodromal disease stages — and proposes an evidence-informed framework for building biomarker-specific privacy and antidiscrimination policy.","key_result":"Existing federal laws leave critical gaps: GINA excludes life, long-term care, and disability insurance; the ADA requires overt symptoms to qualify as a disability; and HIPAA allows health information disclosure for treatment and payment purposes. Preclinical/prodromal individuals — who may still be employed or seeking insurance — are most exposed. A proposed 'BINA' (Biomarker Information Non-Discrimination Act) modeled on GINA is identified as a potential but imperfect solution.","limitations":"This is a legal and policy analysis with no primary empirical data; evidence on actual observed discrimination against biomarker-tested individuals is currently lacking. State-level legal variation and research-record protections are explicitly outside the article's scope.","practice_takeaway":"Until stronger protections exist, clinicians should inform patients and research participants about privacy and discrimination risks tied to biomarker testing — including the option to keep research results out of the clinical medical record. Consent documents for neurodegenerative biomarker research should explicitly address these legal gaps."}},{"doi":"10.1212/wnl.0000000000218121","pmid":"42348807","title":"Alpha-Synuclein Seed Amplification Assay in CSF, Skin, and Submandibular Gland From Incidental Lewy Body Disease and Parkinson Disease","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-06-25T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218121","source_score":14,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-05T13:23:02.977Z","updated_at":"2026-08-05T13:23:02.977Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"condition","value":"Incidental Lewy Body Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"condition","value":"Lewy Body Disorders","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"generic","value":"alpha-synuclein seed amplification assay","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"modality","value":"Biomarker Assay","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"sample_size","value":"n=74","value_numeric":74},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"study_design","value":"Cross-Sectional Autopsy Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"warning","value":"Impact flag 'practice_changing' applied cautiously — authors themselves describe results as 'preliminary'; clinical adoption of CSF-over-peripheral-biopsy strategy should await larger prospective validation.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"warning","value":"Sample sizes for tissue-specific subgroups (especially PD skin and SMG, n=8) are very small; sensitivity and specificity estimates carry wide confidence intervals not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218121","tag_type":"warning","value":"The autopsy-based design means timing of tissue collection relative to disease stage is fixed at death, which may not reflect the sensitivity achievable in living, earlier-stage patients.","value_numeric":null}],"summaries":{"what_studied":"RT-QuIC alpha-synuclein seed amplification assays (SAA) were compared across three tissues — CSF, skin, and submandibular gland (SMG) — in autopsy-confirmed cases of incidental Lewy body disease (ILBD, n=40), Parkinson disease (PD, n=15), and controls (n=19) from the AZSAND cohort, correlated with Unified Staging System for Lewy Body Disorders (USSLB) stage.","key_result":"In ILBD, CSF sensitivity (75.8%, 25/33) far exceeded SMG (35.1%, 13/37) and skin (37.5%, 6/16). In PD, all three tissues showed high sensitivity: CSF 100% (10/10), SMG 87.5% (7/8), and skin 87.5% (7/8). Specificity was similar across tissues (~75–89%). CSF was the only tissue to detect USSLB Stage I (olfactory bulb only) ILBD.","limitations":"- Very small sample sizes, especially for PD tissue subgroups (n=8–10 per tissue), limiting generalizability.\n- Autopsy-based design means findings may not directly translate to live clinical testing scenarios.\n- Not all cases had all three tissues available, introducing potential selection bias.","practice_takeaway":"For detecting prodromal Lewy body disease, CSF alpha-synuclein SAA appears substantially more sensitive than skin or submandibular gland biopsy, particularly at early USSLB stages. Clinicians should prioritize CSF-based aSyn SAA when screening for ILBD or early PD, as peripheral tissue biopsies may miss a significant proportion of cases."}},{"doi":"10.1212/wnl.0000000000218214","pmid":"42308449","title":"Neurologic Diagnoses Before and After Traumatic Brain Injury","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-06-17T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218214","source_score":67,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-14T13:24:23.465Z","updated_at":"2026-07-14T13:24:23.465Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"condition","value":"Epilepsy","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"condition","value":"Stroke","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"condition","value":"Traumatic Brain Injury","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"sample_size","value":"n=55204","value_numeric":55204},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"warning","value":"Impact flag 'practice_changing' was applied cautiously — the study supports a directional shift in fall/injury prevention counseling for neurologic patients, but no formal clinical guideline yet exists based on this data.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"warning","value":"The cohort is 96.5% male and drawn exclusively from US Veterans Health Affairs, so findings may not apply to women or the general population.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218214","tag_type":"warning","value":"Total sample size of 55,204 reflects both TBI (13,801) and matched non-TBI (41,403) cohorts combined.","value_numeric":null}],"summaries":{"what_studied":"This retrospective cohort study examined the bidirectional relationship between acute TBI and four neurologic conditions (stroke, dementia, epilepsy, Parkinson disease) in US Veterans aged ≥55 years (n=13,801 TBI; n=41,403 matched controls), comparing incidence rates in the year before vs. after TBI and vs. a non-TBI cohort over a two-year period (Oct 1999–Sept 2021).","key_result":"Before TBI, Veterans had 3–4× higher incidence of all four conditions vs. non-TBI controls (stroke IRR 3.2, dementia IRR 3.1, PD IRR 3.0, epilepsy IRR 4.4). After TBI, stroke (IRR 1.83) and epilepsy (IRR 2.29) rates roughly doubled and dementia rose modestly (IRR 1.24) compared to the pre-TBI year; PD rates did not increase significantly post-TBI (IRR 1.06).","limitations":"- Cohort is 96.5% male older Veterans, limiting generalizability to women and non-Veteran populations.\n- Diagnoses rely on ICD codes, which may misclassify conditions or miss sub-clinical disease.\n- Residual confounding from unmeasured comorbidities or health-care-seeking behavior cannot be excluded.","practice_takeaway":"Patients with stroke, epilepsy, dementia, or PD carry a substantially elevated pre-TBI risk — clinicians should proactively address fall and injury prevention in these groups. After a TBI, closely monitor for new-onset stroke and epilepsy, which roughly double in incidence within one year."}},{"doi":"10.1212/wnl.0000000000218175","pmid":"42302222","title":"Fecal Microbiota Transplantation in Parkinson Disease","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-06-16T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218175","source_score":11,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-26T13:25:35.423Z","updated_at":"2026-06-26T13:25:35.423Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"generic","value":"fecal microbiota transplantation","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"modality","value":"Fecal Microbiota Transplantation","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"sample_size","value":"n=220","value_numeric":220},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"study_design","value":"Systematic Review and Meta-Analysis","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"warning","value":"High heterogeneity is implied by the wide confidence intervals and mixed study designs, though specific I² values are not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"warning","value":"The meta-analysis pools RCTs and observational studies; the overall estimates are driven partly by non-randomized data and should be interpreted cautiously, as the authors themselves note.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218175","tag_type":"warning","value":"The PROSPERO registration number appears to contain a typo in the abstract (CRD420251142846); verify against the full publication.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and meta-analysis evaluated the efficacy and safety of fecal microbiota transplantation (FMT) in adults with mild-to-moderate Parkinson disease (PD), pooling data from 5 RCTs and 3 observational studies (n=220) searched through September 2025. Primary outcome was motor function (UPDRS part III); secondary outcomes included UPDRS part II, quality of life (PDQ-39), constipation (Wexner score), and adverse events.","key_result":"FMT significantly improved motor function (UPDRS part III MD −9.67, 95% CI −16.81 to −2.53; RCT-only: MD −6.82, 95% CI −11.23 to −2.40) and constipation severity (Wexner MD −3.91, 95% CI −7.68 to −0.13). Improvements in daily living (UPDRS part II) and quality of life (PDQ-39) were seen at 12 weeks but not sustained at 24 weeks. Gastrointestinal adverse events were more frequent with FMT (RR 3.12, 95% CI 1.14–8.53), though mostly mild to moderate.","limitations":"- Very small total sample (n=220 across 8 studies) limits precision and generalizability.\n- Significant heterogeneity across studies and inclusion of observational data; pooled estimates should be interpreted with caution.\n- Short and variable follow-up; motor and QoL benefits were not sustained beyond 12–24 weeks.","practice_takeaway":"FMT may offer short-term motor and constipation relief in mild-to-moderate PD, but benefits appear transient and evidence remains preliminary. Clinicians should not adopt FMT as routine PD therapy until larger, well-powered RCTs confirm durability and safety."}},{"doi":"10.1001/jamaneurol.2026.1634","pmid":"42258190","title":"Pathology and Genetics in a Global Cohort of Parkinsonian Disorders","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-06-08T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13247843/","source_score":31,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-17T13:29:42.103Z","updated_at":"2026-06-17T13:29:42.103Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Corticobasal Syndrome","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Dementia With Lewy Bodies","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Multiple System Atrophy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Parkinson Disease Dementia","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Progressive Supranuclear Palsy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"generic","value":"GBA1 variant","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"generic","value":"LRRK2 variant","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"sample_size","value":"n=3353","value_numeric":3353},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"warning","value":"Full text was not accessible; summary is based solely on the abstract and results excerpt. Some detail (e.g., subgroup breakdowns, covariate adjustments) may be missing.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"warning","value":"GBA1 and LRRK2 are tagged as 'generic' drug names as a best fit; they are genetic variants, not drugs — no standard drug tag type exists for genetic markers.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"warning","value":"Level of evidence assigned as 3 (retrospective cross-sectional brain bank study); some may classify brain bank autopsy studies differently depending on framework used.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously — the scale and multiancestry nature of the findings are notable, but the retrospective and autopsy-selected design limits direct clinical translation.","value_numeric":null}],"summaries":{"what_studied":"This multicenter, retrospective, autopsy-confirmed brain bank study evaluated clinicopathological correlation, diagnostic accuracy, genetic associations with pathology, and ancestry-related differences in 3,353 donors with parkinsonian disorders (or neurologically normal controls) from 11 academic brain banks in the UK, US, and Australia (enrolled 1985–2024).","key_result":"Misdiagnosis rates ranged from ~10–20% across movement disorders. Dementia with parkinsonism (PDD/DLB) was more strongly linked to Lewy body pathology than PD without dementia (OR 1.96; 95% CI 1.30–3.04). GBA1 carriers had greater Lewy body burden than noncarriers (OR 1.94) and LRRK2 carriers (OR 7.44). AD copathology was present in 40% of Lewy body disease cases. Ancestry-related differences in pathology were significant: South Asian donors were more likely to have PSP pathology; Ashkenazi Jewish donors were more likely to have Lewy body disease (independent of GBA1/LRRK2 status).","limitations":"- Brain bank cohorts have inherent selection bias (donors who consent to autopsy may not represent the broader parkinsonian population).\n- The study is cross-sectional and retrospective, limiting causal inference.\n- Full-text data were not available for detailed review; only abstract and results sections were accessible.","practice_takeaway":"Clinicians should anticipate ~10–20% misdiagnosis rates in parkinsonian disorders and recognize that AD copathology is common in Lewy body disease (40% of cases). Genetic profiling (especially GBA1 status) and patient ancestry should inform diagnostic workup and future trial stratification."}},{"doi":"10.1212/wnl.0000000000218072","pmid":"42247653","title":"Drivers of Rising Prevalence in Major Motor Neurodegenerative Diseases","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-06-05T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218072","source_score":21,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-12T13:24:35.513Z","updated_at":"2026-06-12T13:24:35.513Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"condition","value":"Motor Neuron Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"condition","value":"Multiple Sclerosis","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"modality","value":"Disease-Modifying Therapy","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"sample_size","value":"n=700000","value_numeric":700000},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"study_design","value":"Retrospective Population-Based Cohort Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"warning","value":"COVID-19 pandemic years (2020–2022) were excluded from MND incidence regression but retained in curves, which may slightly affect MND trend interpretation.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"warning","value":"Sample size reported as approximate; the paper provides disease-specific prevalent counts (e.g., 227,594 PD in France in 2022) but no single total N across all diseases and years is stated—numeric tag reflects a conservative lower-bound estimate.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"warning","value":"Study periods for Sweden and France do not fully overlap, which may affect pooled trend estimates; authors acknowledge this as a limitation.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218072","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously: findings reframe epidemiologic understanding and have direct health planning implications, though no new treatment is introduced.","value_numeric":null}],"summaries":{"what_studied":"Two nationwide, population-based retrospective cohort studies in Sweden (2003–2016) and France (2011–2022) examined temporal trends in prevalence, incidence, age at diagnosis, and life expectancy for Parkinson disease (PD), multiple sclerosis (MS), and motor neuron diseases (MNDs) to determine whether rising prevalence is driven by increased incidence or improved survival.","key_result":"Prevalence rose annually for all three diseases (PD: +1.4%/yr, MS: +2.9%/yr, MND: +2.8%/yr). MS rising prevalence was largely survival-driven (life expectancy at diagnosis +2.35 months/yr). MND showed a true incidence increase (standardized IRR +0.8%/yr). PD had stable-to-declining standardized incidence with plateauing life expectancy gains (life expectancy at PD diagnosis fell −1.20 months/yr from 2013–2022), explaining its slower prevalence rise.","limitations":"- Results from two high-income European countries with universal healthcare may not generalize to lower-resource or non-Western settings.\n- Case identification relied on administrative codes ± prescriptions, without clinical onset dates, limiting assessment of diagnostic delays.\n- Non-overlapping study periods between countries complicate direct cross-country comparisons.","practice_takeaway":"Rising MS prevalence reflects improved survival, likely from disease-modifying therapies—supporting continued investment in MS treatment access. Rising MND prevalence signals a genuine incidence increase, warranting closer attention to environmental and occupational risk factors rather than assuming it is an artifact of aging or better detection."}},{"doi":"10.1001/jamaneurol.2026.0989","pmid":"42081229","title":"Phenoconversion in Pure Autonomic Failure","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-05-04T00:00:00.000Z","url":"https://doi.org/10.1001/jamaneurol.2026.0989","source_score":27,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:49:12.024Z","updated_at":"2026-05-07T22:49:12.024Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"condition","value":"Alpha-Synucleinopathy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"condition","value":"Dementia With Lewy Bodies","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"condition","value":"Multiple System Atrophy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"condition","value":"Pure Autonomic Failure","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"sample_size","value":"n=900","value_numeric":900},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"study_design","value":"Systematic Review and Meta-Analysis","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"warning","value":"Mean age at onset (63.1 years) and 63.8% male composition may limit generalizability to all PAF populations.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"warning","value":"Only 9 studies met inclusion criteria, limiting subgroup precision, especially for PD-specific conversion rates (wide CIs: 0.75–2.41).","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0989","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — while conversion rates are well-quantified, no disease-modifying therapies for PAF phenoconversion currently exist; the clinical value lies primarily in prognostication and trial enrollment.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and meta-analysis evaluated phenoconversion rates from pure autonomic failure (PAF) to central α-synucleinopathies (PD, DLB, MSA) and identified clinical predictors of phenoconversion across 9 longitudinal studies (n=900; mean follow-up 6.4 years).","key_result":"30% of PAF patients converted to a central α-synucleinopathy (~5.09 per 100 person-years; 95% CI 3.79–6.85): 12% to MSA, 11% to DLB, and 7% to PD. MSA conversion was frontloaded (IR 1.96), while Lewy body disorders converted at steadier rates. RBD and subtle motor signs predicted conversion to any synucleinopathy; hyposmia distinguished PD/DLB from MSA (pooled RR 1.88; 95% CI 1.26–2.97).","limitations":"Only 9 studies with 900 participants were included; heterogeneity was partly explained by follow-up duration, suggesting variability in cohort design. No biomarker data were available for pooled analysis.","practice_takeaway":"Clinicians should monitor PAF patients closely for RBD, subtle motor signs, and hyposmia—each raises the likelihood of phenoconversion to a specific synucleinopathy at a rate comparable to isolated RBD. Early identification of these features may allow timely referral and enrollment in neuroprotective trials."}},{"doi":"10.1212/wnl.0000000000214989","pmid":"42018961","title":"Virtual vs In-Person Neurologic Ambulatory Care","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-04-22T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000214989","source_score":51,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-30T13:22:52.830Z","updated_at":"2026-05-30T13:22:52.830Z","tags":[{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"condition","value":"Headache","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"condition","value":"Multiple Sclerosis","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"condition","value":"Neurologic Disorders","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"modality","value":"Telemedicine","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"sample_size","value":"n=16404","value_numeric":16404},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"warning","value":"Data sourced from Vizient Clinical Data Base — administrative data may have coding limitations for neurologic diagnoses and outcomes.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"warning","value":"Sample size reported is for matched pairs (8,202 + 8,202 = 16,404); total pre-match cohort was 47,195 visits — the sample_size tag reflects the matched analytic sample.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"warning","value":"Sex/gender breakdown was not reported in the available abstract or results text; sex tag omitted.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214989","tag_type":"warning","value":"Study period (Sept 2020–Dec 2021) represents early pandemic-era telemedicine expansion; workflows and patient selection may differ from current practice.","value_numeric":null}],"summaries":{"what_studied":"This retrospective, propensity score-matched multicenter cohort study compared downstream health care utilization (neurology follow-up, ED visits, hospitalizations, and testing) after virtual vs. in-person new outpatient neurology visits at 3 academic medical centers from September 2020 through December 2021 (n = 8,202 matched pairs).","key_result":"90-day neurology follow-up was similar between virtual and in-person visits (24.6% vs 23.7%, p = 0.18), as were 90-day neurologic ED visits (0.9% vs 0.8%, p = 0.23), neurologic hospitalizations (1.8% vs 1.7%, p = 0.47), and all-cause ED visits/hospitalizations; testing was more frequent after some in-person visits, and follow-up patterns varied modestly by chief complaint (e.g., higher after in-person for dementia, higher after virtual for Parkinson disease, MS, and headache).","limitations":"Retrospective design limits causal inference; study covers only 3 academic medical centers, limiting generalizability to community settings; the data period (2020–2021) reflects early COVID-era telemedicine practices that may not reflect current virtual care.","practice_takeaway":"For most new neurology patients, virtual visits appear safe and yield comparable follow-up and emergency utilization as in-person visits. Clinicians may consider in-person evaluation for new dementia patients, where follow-up rates were higher after face-to-face encounters."}},{"doi":"10.1001/jamaneurol.2026.0590","pmid":"41860533","title":"Fixed-Dose Tavapadon for Early Parkinson Disease","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-03-20T00:00:00.000Z","url":"https://doi.org/10.1001/jamaneurol.2026.0590","source_score":65,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:23.859Z","updated_at":"2026-05-18T13:25:23.859Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"generic","value":"tavapadon","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"modality","value":"Dopamine D1/D5 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"sample_size","value":"n=529","value_numeric":529},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"warning","value":"Effect sizes (Cohen's d ~1.1–1.2) are notably large for a motor symptom trial; clinicians should note these are from an industry-sponsored phase 3 trial and await independent replication.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"warning","value":"No brand name for tavapadon was reported in this paper; the 'brand' tag has been omitted.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0590","tag_type":"warning","value":"The mean participant age was 63.7 years; while classified as 'older_adult,' the sample includes a range of adult ages given the SD of 9.6 years.","value_numeric":null}],"summaries":{"what_studied":"TEMPO-1 evaluated two fixed doses of tavapadon (5 mg and 15 mg once daily) vs. placebo over 27 weeks in 529 adults with early Parkinson disease (<3 years' duration) who were treatment-naive or had <3 months of prior dopaminergic therapy.","key_result":"Both doses significantly improved MDS-UPDRS parts II+III combined scores vs. placebo at week 26: 5 mg showed a treatment difference of -11.5 points (95% CI, -13.8 to -9.2; d = 1.14) and 15 mg showed -12.1 points (95% CI, -14.4 to -9.8; d = 1.20), both P < .001. Common adverse events with tavapadon were nausea (25.4%), headache (16.7%), and dizziness (12.7%); most were mild to moderate and nonserious.","limitations":"- Study duration was only 27 weeks, limiting conclusions about long-term efficacy and motor complications.\n- The trial excluded patients with >3 months of prior dopaminergic therapy, so results may not generalize to more advanced or previously treated PD.\n- Only 35.3% of participants were female, which may limit generalizability across sexes.","practice_takeaway":"Tavapadon 5 mg or 15 mg once daily produced large, clinically meaningful motor improvements in early PD with a manageable side-effect profile. Clinicians may consider it as a once-daily oral option for newly diagnosed PD patients, though long-term data are still needed."}},{"doi":"10.1001/jamaneurol.2026.0577","pmid":"41860544","title":"Tavapadon as Adjunctive Treatment for Parkinson Disease","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-03-20T00:00:00.000Z","url":"https://doi.org/10.1001/jamaneurol.2026.0577","source_score":64,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:23.414Z","updated_at":"2026-05-18T13:25:23.414Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"condition","value":"Motor Fluctuations","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"generic","value":"levodopa","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"generic","value":"tavapadon","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"modality","value":"Dopamine D1/D5 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"sample_size","value":"n=507","value_numeric":507},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"warning","value":"Age eligibility in the protocol was 40–80 years, so 'older_adult' tag applies to a subset of enrolled participants; mean age was 64.9 years.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"warning","value":"No brand name for tavapadon was identified in the source text; the brand tag has been omitted accordingly.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"warning","value":"Tavapadon is described as investigational in the protocol; its regulatory approval status as of the publication date is not confirmed in the provided text.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0577","tag_type":"warning","value":"The full text provided is the clinical trial protocol (Version 3.0, Sep 2021), while the abstract and results sections reflect the final published trial outcomes (JAMA Neurology, 2026). The protocol originally planned 368 subjects; the IARC sample-size re-estimation process led to enrollment of 507 participants, consistent with the pre-specified maximum of 528.","value_numeric":null}],"summaries":{"what_studied":"Phase 3 double-blind RCT (TEMPO-3) evaluating flexible-dose tavapadon (5–15 mg once daily), a selective D1/D5 dopamine agonist, as adjunctive therapy to stable oral levodopa (≥400 mg/day) in adults with Parkinson disease experiencing motor fluctuations over 27 weeks (Sep 2020–Feb 2024), with 4-week safety follow-up across 148 sites in 14 countries.","key_result":"Tavapadon significantly increased daily good on-time (on-time without troublesome dyskinesia) by 1.10 hours vs placebo (1.70 vs 0.60 hours; 95% CI, 0.60–1.70; P<.001) and reduced daily off-time by an additional 0.94 hours vs placebo (−1.88 vs −0.93 hours; 95% CI, −1.48 to −0.41; P<.001). More adverse events occurred with tavapadon vs placebo (71.7% vs 55.1%), but 93.2% were nonserious and mild-to-moderate; most common were nausea (14.3%), dyskinesia (10.0%), and dizziness (7.6%).","limitations":"- The trial excluded patients with MoCA <26, Hoehn & Yahr >3, or significant comorbidities, limiting generalizability to more advanced or cognitively impaired PD populations.\n- Levodopa dose was held fixed throughout, so the benefit of combined dose optimization cannot be assessed.\n- Maximum follow-up was 27 weeks; long-term efficacy and safety of this novel mechanism remain unknown.","practice_takeaway":"For PD patients on levodopa with motor fluctuations, adjunctive tavapadon (5–15 mg once daily) adds about 1 hour of good on-time and cuts off-time by nearly 1 hour, with a mainly mild-to-moderate AE profile that avoids the impulse control and somnolence risks linked to D2/D3 agonists. Clinicians should monitor for nausea and dyskinesia, especially during the titration phase."}},{"doi":"10.1212/wnl.0000000000214811","pmid":"41855450","title":"Striatal Dopamine Transporter and Rest Tremor in Parkinson Disease","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-03-19T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000214811","source_score":90,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:51:20.861Z","updated_at":"2026-05-07T22:51:20.861Z","tags":[{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"condition","value":"Parkinsonism","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"generic","value":"ioflupane I-123","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"modality","value":"Dopamine Transporter SPECT Imaging","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"sample_size","value":"n=414","value_numeric":414},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"study_design","value":"Observational Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"warning","value":"DAT binding increase is interpreted as a functional/compensatory change, not neuronal proliferation — this is a hypothesis, not a confirmed mechanism.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"warning","value":"Only right-handed patients were included, which may limit applicability to left-handed individuals given known hemispheric lateralization effects.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"warning","value":"The non-PD abnormal SPECT group was diagnostically heterogeneous (MSA, PSP, and others pooled), making subgroup comparisons unreliable.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214811","tag_type":"warning","value":"The study is cross-sectional; causal direction between ipsilateral DAT binding and rest tremor cannot be established.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional observational study examined the association between striatal DAT binding (via [¹²³I]FP-CIT SPECT) and parkinsonian motor symptoms — rest tremor amplitude, bradykinesia, and rigidity — in 414 right-handed patients referred for diagnostic SPECT in Finland, with a median follow-up of 3.0 years for diagnostic confirmation.","key_result":"In 148 patients with confirmed PD, rest tremor amplitude was positively associated with **ipsilateral** striatal DAT binding (left: β = +0.12 SBR/point [95% CI +0.05, +0.19]; right: β = +0.10 [+0.05, +0.15]; both pFWE+Bonf. < 0.05). Bradykinesia and rigidity showed the expected **negative** association with **contralateral** striatal DAT binding. No consistent tremor–DAT associations were found in non-PD groups.","limitations":"- Image registration lacked separate anatomical MRI, risking spatial misalignment and signal spillover.\n- Non-PD comparison groups were diagnostically heterogeneous, preventing conclusions about disease specificity.\n- Only right-handed patients were included and the cohort was referred for SPECT due to diagnostic uncertainty, limiting generalizability.","practice_takeaway":"In PD, higher ipsilateral striatal DAT binding correlates with greater rest tremor amplitude — a pattern distinct from bradykinesia and rigidity, which track contralateral dopaminergic loss. Clinicians should recognize rest tremor as pathophysiologically separate from other cardinal PD motor features, though DAT SPECT cannot yet be used to predict or guide tremor management."}},{"doi":"10.1038/s41582-025-01179-3","pmid":"41513745","title":"An updated definition of freezing of gait","journal_title":"Nature Reviews Neurology","journal_issn":"1759-4758","published_at":"2026-01-10T00:00:00.000Z","url":"https://doi.org/10.1038/s41582-025-01179-3","source_score":25,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-10","doi":"10.1038/s41582-025-01179-3","days":"14","issn":"1759-4758","rank":"6","field":"Clinical Medicine","score":"25","category":"Clinical Neurology","categories":["Clinical Neurology"],"_categories":["Clinical Neurology"]},"pubmed":{"doi":"10.1038/s41582-025-01179-3","title":"An updated definition of freezing of gait.","journal":"Nature reviews. Neurology","methods":"","results":"","abstract":"Freezing of gait (FOG) is among the most debilitating symptoms of Parkinson disease and related disorders, often resulting in falls and a loss of independence. FOG has an episodic and heterogeneous nature that makes it difficult to measure and treat. The field currently lacks a consensus on how to precisely define this phenomenon. For this reason, the International Consortium for Freezing of Gait convened a group of experts to establish an updated 'clinical' definition of FOG for use in the clinical setting and a 'technical' definition for assessors to use when scoring FOG episodes from video recordings as an outcome in fundamental research and clinical trials. Guidelines on how to classify people with Parkinson disease into subgroups of those with or without FOG (non-FOG) are also provided. 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Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"modality","value":"Positive Airway Pressure","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"sample_size","value":"n=11,310,411","value_numeric":11310411},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"warning","value":"As an observational veteran cohort study, residual confounding and limited generalizability are possible.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"warning","value":"OSA and CPAP exposure were derived from administrative codes and a semistructured EHR field, which may misclassify patients.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"warning","value":"The absolute risk difference reported is small (1.61 per 1000 at 6 years).","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2025.4691","tag_type":"warning","value":"The definition and measurement of “early” CPAP use are not clearly specified.","value_numeric":null}],"summaries":{"what_studied":"An EHR-based cohort of US veterans (1999-2022; mean follow-up 4.9 years) examined whether obstructive sleep apnea (OSA) is associated with incident Parkinson disease (PD) and whether early continuous positive airway pressure (CPAP) modifies risk, accounting for competing risk of death and balancing for age, race, sex, and smoking.","key_result":"Among 11,310,411 veterans (1,552,505 with OSA), OSA was associated with 1.61 additional PD cases per 1000 people at 6 years (95% CI, 1.13-2.09) versus no OSA; estimates were robust to adjustment for BMI, vascular and psychiatric comorbidities, and medications, were larger in women, and PD case numbers were significantly reduced with early CPAP use.","limitations":"OSA was identified by administrative codes and CPAP by a semistructured interview field, which may misclassify exposure and treatment; timing of “early” CPAP was not precisely defined; findings come from a veteran cohort, which may limit generalizability and leave residual confounding.","practice_takeaway":"In this large veteran cohort, OSA was linked to a small absolute increase in 6-year PD incidence, and early CPAP use was associated with fewer PD cases. Clinicians should ensure effective OSA screening and support consistent CPAP use when indicated."}}],"initialOffset":21,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Parkinson Disease"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Parkinson Disease"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Parkinson Disease"}}}]]

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