Asterios Chrysou, Tuomas Heikka, Sygrid van der Zee, Jeffrey M Boertien, Nomdo M Jansonius, Teus van Laar
{"title":"Reduced Thickness of the Retina in de novo Parkinson's Disease Shows A Distinct Pattern, Different from Glaucoma.","authors":"Asterios Chrysou, Tuomas Heikka, Sygrid van der Zee, Jeffrey M Boertien, Nomdo M Jansonius, Teus van Laar","doi":"10.3233/JPD-223481","DOIUrl":"10.3233/JPD-223481","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) patients experience visual symptoms and retinal degeneration. Studies using optical coherence tomography (OCT) have shown reduced thickness of the retina in PD, also a key characteristic of glaucoma.</p><p><strong>Objective: </strong>To identify the presence and pattern of retinal changes in de novo, treatment-naive PD patients compared to healthy controls (HC) and early primary open angle glaucoma (POAG) patients.</p><p><strong>Methods: </strong>Macular OCT data (10×10 mm) were collected from HC, PD, and early POAG patients, at the University Medical Center Groningen. Bayesian informative hypotheses statistical analyses were carried out comparing HC, PD-, and POAG patients, within each retinal cell layer.</p><p><strong>Results: </strong>In total 100 HC, 121 PD, and 78 POAG patients were included. We showed significant reduced thickness of the inner plexiform layer and retinal pigment epithelium in PD compared to HC. POAG patients presented with a significantly thinner retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, outer plexiform layer, and outer photoreceptor and subretinal virtual space compared to PD. Only the outer segment layer and retinal pigment epithelium were significantly thinner in PD compared to POAG.</p><p><strong>Conclusions: </strong>De novo PD patients show reduced thickness of the retina compared to HC, especially of the inner plexiform layer, which differs significantly from POAG, showing a more extensive and widespread pattern of reduced thickness across layers. OCT is a useful tool to detect retinal changes in de novo PD, but its specificity versus other neurodegenerative disorders has to be established.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"507-519"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Parkinson's Disease is Predominantly a Genetic Disease.","authors":"Shen-Yang Lim, Christine Klein","doi":"10.3233/JPD-230376","DOIUrl":"10.3233/JPD-230376","url":null,"abstract":"<p><p>The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene in the Contursi kindred in 1997 indisputably confirmed a genetic cause in a subset of Parkinson's disease (PD) patients. Currently, pathogenic variants in one of the seven established PD genes or the strongest known risk factor gene, GBA1, are identified in ∼15% of PD patients unselected for age at onset and family history. In this Debate article, we highlight multiple avenues of research that suggest an important - and in some cases even predominant - role for genetics in PD aetiology, including familial clustering, high rates of monogenic PD in selected populations, and complete penetrance with certain forms. At first sight, the steep increase in PD prevalence exceeding that of other neurodegenerative diseases may argue against a predominant genetic etiology. Notably, the principal genetic contribution in PD is conferred by pathogenic variants in LRRK2 and GBA1 and, in both cases, characterized by an overall late age of onset and age-related penetrance. In addition, polygenic risk plays a considerable role in PD. However, it is likely that, in the majority of PD patients, a complex interplay of aging, genetic, environmental, and epigenetic factors leads to disease development.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"467-482"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher J Lovegrove, Ingrid H W M Sturkenboom, Jonathan Marsden, Katrina Bannigan
{"title":"Erratum to: Concept Mapping to Define Components for an Occupation-Based Intervention for Parkinson's Disease and Anxiety.","authors":"Christopher J Lovegrove, Ingrid H W M Sturkenboom, Jonathan Marsden, Katrina Bannigan","doi":"10.3233/JPD-249010","DOIUrl":"10.3233/JPD-249010","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1531"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Approaches to Early Parkinson's Disease Subtyping.","authors":"Michele Hu, Casper Skjærbæk, Per Borghammer","doi":"10.3233/JPD-230419","DOIUrl":"10.3233/JPD-230419","url":null,"abstract":"<p><p>Parkinson's disease (PD) unfolds with pathological processes and neurodegeneration well before the emergence of noticeable motor symptoms, providing a window for early identification. The extended prodromal phase allows the use of risk stratification measures and prodromal markers to pinpoint individuals likely to develop PD. Importantly, a growing body of evidence emphasizes the heterogeneity within prodromal and clinically diagnosed PD. The disease likely comprises distinct subtypes exhibiting diverse clinical manifestations, pathophysiological mechanisms, and patterns of α-synuclein progression in the central and peripheral nervous systems. There is a pressing need to refine the definition and early identification of these prodromal subtypes. This requires a comprehensive strategy that integrates genetic, pathological, imaging, and multi-omics markers, alongside careful observation of subtle motor and non-motor symptoms. Such multi-dimensional classification of early PD subtypes will improve our understanding of underlying disease pathophysiology, improve predictions of clinical endpoints, progression trajectory and medication response, contribute to drug discovery and personalized medicine by identifying subtype-specific disease mechanisms, and facilitate drug trials by reducing confounding effects of heterogeneity. Here we explore different subtyping methodologies in prodromal and clinical PD, focusing on clinical, imaging, genetic and molecular subtyping approaches. We also emphasize the need for refined, theoretical a priori disease models. These will be prerequisite to understanding the biological underpinnings of biological subtypes, which have been defined by large scale data-driven approaches and multi-omics fingerprints.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S297-S306"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seo Yeon Yoon, Ja Young Choi, Ga Eun Nam, Jin-Hyung Jung, Kyungdo Han, Sung Hoon Kang, Chi Kyung Kim, Yong Wook Kim, Seong-Beom Koh
{"title":"Association Between Body Mass Index Changes and All-Cause Mortality in Parkinson's Disease.","authors":"Seo Yeon Yoon, Ja Young Choi, Ga Eun Nam, Jin-Hyung Jung, Kyungdo Han, Sung Hoon Kang, Chi Kyung Kim, Yong Wook Kim, Seong-Beom Koh","doi":"10.3233/JPD-240181","DOIUrl":"10.3233/JPD-240181","url":null,"abstract":"<p><strong>Background: </strong>Whether body weight changes are associated with Parkinson's disease (PD) mortality remains uncertain.</p><p><strong>Objective: </strong>To investigate the association between changes in body mass index (BMI) and all-cause mortality in patients with PD.</p><p><strong>Methods: </strong>This nationwide cohort study enrolled 20,703 individuals with new-onset PD (ICD-10 code: G20 and a rare intractable disease registration code: V124) who underwent health screening program by the Korean National Health Insurance Service within two years from pre- and post-PD diagnosis. We identified nine BMI change groups based on three BMI status: underweight (BMI < 18.5 kg/m2), normal or overweight (18.5 kg/m2≤BMI < 25 kg/m2), and obese (BMI≥25 kg/m2).</p><p><strong>Results: </strong>Of 20,703 individuals, 3,789 (18.0%) died during the follow-up period. Excessive weight loss to underweight in the obese group (hazard ratio [HR] = 3.36, 95% CI:1.60-7.08), weight loss in the normal to overweight group (HR = 2.04, 95% CI:1.75-2.39), sustained underweight status (HR = 2.05, 95% CI:1.67-2.52), and weight gain from underweight to normal or overweight (HR = 1.52, 95% CI:1.15-2.02) were associated with increased mortality. Sustained obese status (HR = 0.80, 95% CI:0.74-0.87) and weight gain in the normal to overweight group (HR = 0.82, 95% CI:0.71-0.95) were associated with reduced mortality.</p><p><strong>Conclusions: </strong>We found that BMI change at diagnosis was associated with mortality in patients with PD. Specifically, being underweight either before or after diagnosis as well as experiencing weight loss, were associated with increased mortality. These findings provide valuable insights for weight management planning in PD, highlighting the importance of individualized approach that consider pre-diagnosis BMI.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1441-1450"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vasilija Stopic, Stefanie T Jost, Julius Haupt, Gregor A Brandt, Christina van der Linden, Jan Niklas Petry-Schmelzer, Till A Dembek, Gereon R Fink, Lucia Batzu, Alexandra Rizos, K Ray Chaudhuri, Haidar S Dafsari, Doreen Gruber, Georg Ebersbach, Josef Kessler, Michael T Barbe, Anna Sauerbier
{"title":"Validation Study of the Parkinson's Disease Stigma Questionnaire (PDStigmaQuest).","authors":"Vasilija Stopic, Stefanie T Jost, Julius Haupt, Gregor A Brandt, Christina van der Linden, Jan Niklas Petry-Schmelzer, Till A Dembek, Gereon R Fink, Lucia Batzu, Alexandra Rizos, K Ray Chaudhuri, Haidar S Dafsari, Doreen Gruber, Georg Ebersbach, Josef Kessler, Michael T Barbe, Anna Sauerbier","doi":"10.3233/JPD-240224","DOIUrl":"10.3233/JPD-240224","url":null,"abstract":"<p><strong>Background: </strong>Stigma is a relevant aspect of Parkinson's disease (PD). Specific stigma tools are needed to address the complex construct of stigma in PD comprehensively.</p><p><strong>Objective: </strong>To test the dimensionality and psychometric properties of the newly developed Parkinson's Disease Stigma Questionnaire (PDStigmaQuest).</p><p><strong>Methods: </strong>In this multi-center, cross-sectional study including PD patients and healthy controls, the dimensionality of the PDStigmaQuest was examined through exploratory factor analysis. Acceptability and psychometric properties were investigated. PDStigmaQuest scores of patients and healthy controls were compared.</p><p><strong>Results: </strong>In total, 201 PD patients and 101 healthy controls were included in the final analysis. Results suggested high data quality of the PDStigmaQuest (0.0001% missing data for patients). The exploratory factor analysis produced four factors: felt stigma, hiding, enacted stigma: rejection, and enacted stigma: patronization, explaining 47.9% of variance. An optional work domain for employed patients was included. Moderate floor effects and skewness, but no ceiling effects were found. Cronbach's alpha of 0.85 indicated high internal consistency. Calculated item-total correlations met standard criteria. Test-retest reliability was high (rs = 0.83). PDStigmaQuest scores correlated significantly with other stigma measures (rs = 0.56-0.69) and were significantly higher in patients than in healthy controls and higher in patients with depressive symptoms than in those without.</p><p><strong>Conclusions: </strong>The patient-reported 18-item PDStigmaQuest showed strong psychometric properties of validity and reliability. Our results suggest that the PDStigmaQuest can be used to assess and evaluate stigma comprehensively in PD, which will improve our understanding of the construct of PD stigma.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1469-1480"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hidden Gems in Neurology: The Syndrome of Hemiparkinsonism-Hemiatrophy.","authors":"Sojung Kara Park, Peter A LeWitt","doi":"10.3233/JPD-240290","DOIUrl":"10.3233/JPD-240290","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"14 7","pages":"1519-1525"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Special Issue: Non-Pharmacological Interventions for People with Parkinson's Disease: Are We Entering a New Era?","authors":"E Kalbe, B R Bloem, L V Kalia, A Nieuwboer","doi":"10.3233/JPD-249009","DOIUrl":"10.3233/JPD-249009","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"14 s1","pages":"S1-S4"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hendrik Theis, Nicola Pavese, Irena Rektorová, Thilo van Eimeren
{"title":"Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson's Disease.","authors":"Hendrik Theis, Nicola Pavese, Irena Rektorová, Thilo van Eimeren","doi":"10.3233/JPD-230385","DOIUrl":"10.3233/JPD-230385","url":null,"abstract":"<p><p>Assessing imaging biomarker in the prodromal and early phases of Parkinson's disease (PD) is of great importance to ensure an early and safe diagnosis. In the last decades, imaging modalities advanced and are now able to assess many different aspects of neurodegeneration in PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT imaging with Ioflupane, more specific PET tracers to assess degeneration of the dopaminergic system are available. Furthermore, metabolic PET patterns can be used to anticipate a phenoconversion from prodromal PD to manifest PD. In this regard, it is worth mentioning that PET imaging of inflammation will gain significance. Molecular imaging of neurotransmitters like serotonin, noradrenaline and acetylcholine shed more light on non-motor symptoms. Outside of the brain, molecular imaging of the heart and gut is used to measure PD-related degeneration of the autonomous nervous system. Moreover, optical coherence tomography can noninvasively detect degeneration of retinal fibers as a potential biomarker in PD. In this review, we describe these state-of-the-art imaging modalities in early and prodromal PD and point out in how far these techniques can and will be used in the future to pave the way towards a biomarker-based staging of PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S353-S365"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Striatal Serotonin 4 Receptor is Increased in Experimental Parkinsonism and Dyskinesia.","authors":"Rossella Cirillo, Sandra Duperrier, Pathik Parekh, Mathilde Millot, Qin Li, Marie-Laure Thiolat, Micaela Morelli, Jing Xie, Didier Le Bars, Jérôme Redouté, Erwan Bezard, Véronique Sgambato","doi":"10.3233/JPD-230331","DOIUrl":"10.3233/JPD-230331","url":null,"abstract":"<p><p>Alterations of serotonin type 4 receptor levels are linked to mood disorders and cognitive deficits in several conditions. However, few studies have investigated 5-HT4R alterations in movement disorders. We wondered whether striatal 5-HT4R expression is altered in experimental parkinsonism. We used a brain bank tissue from a rat and a macaque model of Parkinson's disease (PD). We then investigated its in vivo PET imaging regulation in a cohort of macaques. Dopaminergic depletion increases striatal 5-HT4R in the two models, further augmented after dyskinesia-inducing L-Dopa. Pending confirmation in PD patients, the 5-HT4R might offer a therapeutic target for dampening PD's symptoms.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"261-267"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}