Journal of Parkinson's disease最新文献

{"title":"Letter to the Editor: Is It Too Early to Underrate Genetics onto PD Pathogenesis? Reflections on History.","authors":"Alessandro Stefani","doi":"10.3233/JPD-230430","DOIUrl":"10.3233/JPD-230430","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"14 2","pages":"357-358"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059616","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":"Disease Progression of Data-Driven Subtypes of Parkinson's Disease: 5-Year Longitudinal Study from the Early Parkinson's Disease Longitudinal Singapore (PALS) Cohort.","authors":"Xiao Deng, Seyed Ehsan Saffari, Bin Xiao, Samuel Yong Ern Ng, Nicole Chia, Xinyi Choi, Dede Liana Heng, Ebonne Ng, Zheyu Xu, Kay-Yaw Tay, Wing-Lok Au, Eng-King Tan, Louis C S Tan","doi":"10.3233/JPD-230209","DOIUrl":"10.3233/JPD-230209","url":null,"abstract":"<p><strong>Background: </strong>The detailed trajectory of data-driven subtypes in Parkinson's disease (PD) within Asian cohorts remains undisclosed.</p><p><strong>Objective: </strong>To evaluate the motor, non-motor symptom (NMS) progression among the data-driven PD clusters.</p><p><strong>Methods: </strong>In this 5-year longitudinal study, NMS scale (NMSS), Hospital Anxiety Depression Scale (HADS), and Epworth sleepiness scale (ESS) were carried out annually to monitor NMS progression. H& Y staging scale, MDS-UPDRS part III motor score, and postural instability gait difficulty (PIGD) score were assessed annually to evaluate disease severity and motor progression. Five cognitive standardized scores were used to assess detailed cognitive progression. Linear mixed model was performed to assess the annual progression rates of the longitudinal outcomes.</p><p><strong>Results: </strong>Two hundred and six early PD patients, consisting of 43 patients in cluster A, 98 patients in cluster B and 65 subjects in cluster C. Cluster A (severe subtype) had significantly faster progression slope in NMSS Domain 3 (mood/apathy) score (p = 0.01), NMSS Domain 4 (perceptual problems) score (p = 0.02), NMSS Domain 7 (urinary) score (p = 0.03), and ESS Total Score (p = 0.04) than the other two clusters. Cluster A also progressed significantly in PIGD score (p = 0.04). For cognitive outcomes, cluster A deteriorated significantly in visuospatial domain (p = 0.002), while cluster C (mild subtype) deteriorated significantly in executive domain (p = 0.04).</p><p><strong>Conclusions: </strong>The severe cluster had significantly faster progression, particularly in mood and perceptual NMS domains, visuospatial cognitive performances, and postural instability gait scores. Our findings will be helpful for clinicians to stratify and pre-emptively manage PD patients by developing intervention strategies to counter the progression of these domains.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1051-1059"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288215","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":"Pharmacotherapy for Disease Modification in Early Parkinson's Disease: How Early Should We Be?","authors":"Philipp Mahlknecht, Werner Poewe","doi":"10.3233/JPD-230354","DOIUrl":"10.3233/JPD-230354","url":null,"abstract":"<p><p>Slowing or halting progression continues to be a major unmet medical need in Parkinson's disease (PD). Numerous trials over the past decades have tested a broad range of interventions without ultimate success. There are many potential reasons for this failure and much debate has focused on the need to test 'disease-modifying' candidate drugs in the earliest stages of disease. While generally accepted as a rational approach, it is also associated with significant challenges around the selection of trial populations as well as trial outcomes and durations. From a health care perspective, intervening even earlier and before at-risk subjects have gone on to develop overt clinical disease is at the heart of preventive medicine. Recent attempts to develop a framework for a biological definition of PD are aiming to enable 'preclinical' and subtype-specific diagnostic approaches. The present review addresses past efforts towards disease-modification, including drug targets and reasons for failure, as well as novel targets that are currently being explored in disease-modification trials in early established PD. The new biological definitions of PD may offer new opportunities to intervene even earlier. We critically discuss the potential and challenges around planning 'disease-prevention' trials in subjects with biologically defined 'preclinical' or prodromal PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S407-S421"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012818","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":"The Impact of Motor, Non-Motor, and Social Aspects on the Sexual Health of Men Living with Parkinson's Disease.","authors":"Bruno Rafael Antunes Souza, Kátia Cirilo Costa Nóbrega, Bruno Eron de Almeida da Silva, Raissa Amorim Gonçalves, Thalyta Silva Martins, Geovanna Ferreira Santos, André Helene Frazão, Antonio Carlos Roque, Isaíra Almeida Pereira da Silva Nascimento, Maria Elisa Pimentel Piemonte","doi":"10.3233/JPD-230212","DOIUrl":"10.3233/JPD-230212","url":null,"abstract":"<p><strong>Background: </strong>Sexual health (SH) is influenced by several biological, mental, and social factors that may be negatively impacted by Parkinson's disease (PD). Despite its prevalence and relevance for quality of life, the factors that affect SH in men with PD (MwPD) are still poorly understood.</p><p><strong>Objectives: </strong>To investigate the impact of motor, non-motor, and social aspects on the SH in MwPD.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of 80 men (mean-age 53.55±10.8) in stages 1-3 of Hoehn and Yahr classification (H&Y), who reported having an active sex life in the last six months. The following data were collected for each person: 1) Demographic and clinical features; 2) global cognitive capacity (T-MoCA); 3) Non-Motor Aspects of Experiences of Daily Living (MDS-UPDRS, part I); 4) Motor Aspects of Experiences of Daily Living (MDS-UPDRS, part II); 5) Fatigue (FSS); 6) Self-esteem (RSES); 7) Sleep disorder (PDSS); 8) Couple relationship quality (DAS); 9) Depressive signals (BDI); 10) Short-term sexual health by International Index of Erectile Function (IIFE); and 11) Long-term sexual health by Sexual Quotient-Male (SQ-M).</p><p><strong>Results: </strong>Our results showed that although several motor, non-motor, and social factors were correlated with SH, only motor disability levels in daily living predicted short-term SH and erectile dysfunction, while only depression predicted long-term SH in MwPD. Age, disease onset, and medication daily dosage were not correlated with SH.</p><p><strong>Conclusions: </strong>Our findings confirm that multidimensional factors can affect the SH of MwPD and emphasize that only a multi-professional team can offer proper care to improve SH in MwPD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"565-574"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012820","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":"Rapid Voluntary Blinking as a Clinical Marker of Parkinson's Disease.","authors":"Michaela Francis, Alexandra Zirra, Tahrina Haque, David Gallagher, Caroline Budu, Andrew J Lees, Anette Schrag, Alastair J Noyce, Cristina Simonet","doi":"10.3233/JPD-240005","DOIUrl":"10.3233/JPD-240005","url":null,"abstract":"<p><p>Reduced spontaneous blinking is a recognized Parkinson's disease (PD) feature. In contrast, voluntary blinking has been less studied and might serve as a measurable marker of facial bradykinesia. We tested 31 PD patients and 31 controls. Participants were filmed during conversation and a rapid blinking task. Both tasks were videorecorded to count the number of blinks per second. PD patients had lower blink rates. Rapid blinking accurately discriminated between groups with 77% sensitivity and 71% specificity. To conclude, rapid blinking may be a simple and quantifiable task of facial bradykinesia.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"993-997"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468785","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":"Ethical Considerations for Identifying Individuals in the Prodromal/Early Phase of Parkinson's Disease: A Narrative Review.","authors":"Eva Schaeffer, Rezzak Yilmaz, Erik K St Louis, Alastair J Noyce","doi":"10.3233/JPD-230428","DOIUrl":"10.3233/JPD-230428","url":null,"abstract":"<p><p>The ability to identify individuals in the prodromal phase of Parkinson's disease has improved in recent years, raising the question of whether and how those affected should be informed about the risk of future disease. Several studies investigated prognostic counselling for individuals with isolated REM sleep behavior disorder and have shown that most patients want to receive information about prognosis, but autonomy and individual preferences must be respected. However, there are still many unanswered questions about risk disclosure or early diagnosis of PD, including the impact on personal circumstances, cultural preferences and specific challenges associated with different profiles of prodromal symptoms, genetic testing or biomarker assessments. This narrative review aims to summarize the current literature on prognostic counselling and risk disclosure in PD, as well as highlight future perspectives that may emerge with the development of new biomarkers and their anticipated impact on the definition of PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S307-S319"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600237","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":"The AAV-α-Synuclein Model of Parkinson's Disease: An Update.","authors":"Anders Björklund, Bengt Mattsson","doi":"10.3233/JPD-240207","DOIUrl":"10.3233/JPD-240207","url":null,"abstract":"<p><p>Targeted delivery of α-synuclein using AAV vectors has over the two decades since its introduction developed into a versatile tool for modeling different aspects of synucleinopathy, mimicking those seen in Parkinson's disease and related Lewy body disorders. The viral vector approach to disease modeling is attractive in that the expression of α-synuclein, wild-type or mutated, can be confined to defined anatomical structures and targeted to selected cell populations using either cell-type specific promoter constructs or different natural or engineered AAV serotypes. AAV-α-synuclein was initially used to model progressive α-synuclein pathology in nigral dopamine neurons, and, like the standard 6-OHDA model, it has most commonly been applied unilaterally, using the non-injected side as a reference and control. In recent years, however, the AAV-α-synuclein model has become more widely used to induce Parkinson-like synuclein pathology in other relevant neuronal systems, such as the brainstem noradrenergic and serotonergic neurons, the vagal motor neurons, as well as in oligodendrocytes, the prime target relevant to the pathology seen in multiple system atrophy. The purpose of this review is to give an overview of the progress made in the use of the AAV-α-synuclein model over the last two decades and summarize the state-of-the art in the use of the AAV-α-synuclein model for disease modeling in rats and mice.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1077-1094"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731292","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":"Advice to People with Parkinson's in My Clinic: Probiotics and Prebiotics.","authors":"Jia Wei Hor, Tzi Shin Toh, Shen-Yang Lim, Ai Huey Tan","doi":"10.3233/JPD-240172","DOIUrl":"10.3233/JPD-240172","url":null,"abstract":"<p><p>There is increasing evidence that microbial-based therapies can be useful in people with Parkinson's disease (PD). In this viewpoint, we provide a state-of-the-art review of the clinical and pre-clinical evidence for probiotics and prebiotics in PD. Currently, short-term clinical studies, including double-blind placebo-controlled randomized clinical trials, have demonstrated safety, and efficacy primarily in improving constipation-related symptoms. Pre-clinical studies consistently reported improvements in a range of biological markers and outcomes, including evidence for attenuation of gut dysfunction and neuroprotection. Bacteria from the genus Lactobacillus and Bifidobacterium have been the most frequently studied both in clinical and pre-clinical probiotics studies, while research into prebiotics is still limited and primarily involved resistant starch and fructooligosaccharides. We provide practical suggestions for clinicians on how to advise patients in the clinic regarding these popular treatments, and important caveats to be aware of. Finally, areas for further advancements are highlighted. It is envisaged that in the future, microbial-based therapies may benefit from personalization based on an enhanced understanding of a whole range of host factors and host-microbiome interactions.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1507-1518"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108467","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":"Altered Outer Retinal Structure, Electrophysiology and Visual Perception in Parkinson's Disease.","authors":"Katie K N Tran, Pei Ying Lee, David I Finkelstein, Allison M McKendrick, Bao N Nguyen, Bang V Bui, Christine T O Nguyen","doi":"10.3233/JPD-230293","DOIUrl":"10.3233/JPD-230293","url":null,"abstract":"<p><strong>Background: </strong>Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation.</p><p><strong>Objective: </strong>To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing.</p><p><strong>Methods: </strong>Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = 16) and controls (n = 21). Electroretinography and OCT were conducted before and after midday L-DOPA in PD participants, or repeated after ∼2 hours in controls.</p><p><strong>Results: </strong>PD participants had decreased center-surround contrast suppression (p < 0.01), reduced macular visual field sensitivity (p < 0.05), color vision impairment (p < 0.01) photoreceptor dysfunction (a-wave, p < 0.01) and photoreceptor neurodegeneration (outer nuclear layer thinning, p < 0.05), relative to controls. Effect size comparison between inner and outer retinal parameters showed that photoreceptor metrics were similarly robust in differentiating the PD group from age-matched controls as inner retinal changes. Electroretinography and OCT were unaffected by L-DOPA treatment or time.</p><p><strong>Conclusions: </strong>We show that outer retinal outcomes of photoreceptoral dysfunction (decreased cone function and impaired color vision) and degeneration (i.e., outer nuclear layer thinning) were equivalent to inner retinal metrics at differentiating PD from healthy age-matched adults. These findings suggest outer retinal metrics may serve as useful biomarkers for PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"167-180"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377863","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":"DRD3 Predicts Cognitive Impairment and Anxiety in Parkinson's Disease: Susceptibility and Protective Effects.","authors":"Alexandra Gonçalves, Alexandre Mendes, Joana Damásio, Nuno Vila-Chã, Daniela Boleixa, Bárbara Leal, Sara Cavaco","doi":"10.3233/JPD-230292","DOIUrl":"10.3233/JPD-230292","url":null,"abstract":"<p><strong>Background: </strong>A possible genetic contribution of dopamine D3 receptor (DRD3) to cognitive impairment in Parkinson's disease (PD) has yet to be investigated.</p><p><strong>Objective: </strong>To explore the effects of rs6280 (Ser9Gly) genotype on PD patients' cognitive performance and to clarify possible interactions with psychopathology.</p><p><strong>Methods: </strong>Two hundred and fifty-three consecutive PD patients underwent neurological and neuropsychological evaluations, which included: Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Dementia Rating Scale-2 (DRS-2), and Hospital Anxiety and Depression Scale (HADS). rs6280 polymorphism was genotyped for all PD patients and for 270 ethnically matched healthy volunteers (HC). Non-parametric group comparisons and logistic regressions were used for data analyses.</p><p><strong>Results: </strong>rs6280 genotype did not differ between PD and HC groups. PD patients with rs6280 CC genotype had more impaired cognitive performance (i.e., <1st percentile of demographically adjusted norms) on DRS-2 subscales Initiation/Perseveration and Construction than those with TT genotype. These associations remained statistically significant when other covariates (e.g., demographic features, disease duration, severity of motor symptoms in OFF and ON states, anti-parkinsonian medication, and psychopathology symptoms) were taken into consideration. PD patients with rs6280 TC had less anxiety (i.e., HADS Anxiety≥11) than those with TT (p = 0.012). This association was also independent of other covariates.</p><p><strong>Conclusions: </strong>Study findings suggest that rs6280 CC genotype predisposes to executive dysfunction and visuoconstructional deficits, whereas the heterozygous genotype protects from anxiety in PD. These effects do not appear to be dependent of one another. rs6280 is not a genotypic susceptibility factor for PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"313-324"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741289","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}