Criteria For Parkinson's Disease Research Articles

Levodopa Equivalent Daily Dosage: Geographical Variations and Real-Life Modules in Parkinson's Disease.

The Levodopa Equivalent Daily Dosage (LEDD) calculation algorithms help in capturing and harmonization of Parkinson's Disease (PD) therapies. Analyzing these updates is essential for validating their effectiveness. To assess updated LEDD conversion factors in capturing the newer therapies in PD and therapy modules in different geographical cohorts. Data were sourced from 10 Centers from 6 countries representing 2 different continents. The study compared the LEDD conversion factors proposed by Tomlinson et al and Jost et al, alongside investigating demographic disparities. The analysis involved 2943 subjects; 87% (n = 2577) met the UK Brain Bank criteria for PD. The LEDD differed significantly across methodologies (Tomlinson vs. Jost, 598 mg vs 610 mg, P < 0.0001). Geographical disparities highlighted variations in PD onset age (P < 0.0001). Jost and Tomlinson's calculations demonstrated consistency within but significant differences across countries (P < 0.0001).Age at onset revealed statistically significant differences in LEDD requirements (P < 0.0001), which were particularly higher in 21-50 years (718 mg vs 566 mg). This subgroup also demonstrated increased usage of non-Levodopa therapies (P < 0.0001). Men exhibited higher total LEDD (P = 0.001). 34% reported dyskinesia, associated with higher LEDD (756 mg, P < 0.0001). Surgically treated patients also had higher LEDD (P < 0.0001) and a significant difference between Jost and Tomlinson dosages (761 mg vs716mg) reflecting the incorporation of newer therapeutic molecules. This analysis delineates the importance of updated LEDD algorithms and intricacies in the landscape of PD treatment, underscored by geographical, age-related, and gender-specific variations, in real-life management scenarios.

Correlations of erythrocytic oligomer α-synuclein levels with age, sex and clinical variables in patients with Parkinson's disease.

Oligomeric alpha-synuclein in red blood cells (RBC-o-α-Syn) has been shown to be increased in patients with Parkinson's disease (PD). However, factors that affect RBC-o-α-Syn levels remain to be elucidated. The aim of this study is to analyze the correlations between RBC-o-α-Syn levels and the age, sex and different clinical variables of patients with PD. 167 patients with PD and 119 healthy controls (HC) were enrolled in this study. The patients with PD were diagnosed based on the MDS clinical diagnostic criteria for PD. All participants were evaluated for their clinical characteristics. Western blot analysis was used to examine the molecular sizes of RBC-o-α-Syn. A newly established chemiluminescent immunoassay was used to measure RBC-o-α-Syn levels. Higher RBC-o-α-Syn levels were detected in PD patients than in HC subjects. The receiver operating characteristic (ROC) curve indicated that a cut off value of 55.29 ng/mg discriminated well between PD patients and HC subjects, with a sensitivity of 67.66% (95% CI: 60.24-74.29%), a specificity of 88.24% (95% CI: 81.22-92.86%), and an area under the curve (AUC) of 0.857. The levels of RBC-o-α-Syn were higher in female than male patients (p = 0.033). For different subtypes, the levels of RBC-o-α-Syn were higher in the MIX subtype than the tremor-dominant (TD) PD. In addition, the levels of RBC-o-α-Syn were higher in patients with than without cognitive impairment (p = 0.016), and negatively correlated with Mini-Mental State Examination (MMSE) scores (r = -0.156, p = 0.044). Our study demonstrates that RBC-o-α-Syn levels in patients with PD are higher than those in HC subjects and affected by the sex and the severity of cognitive impairment.

Contribution of MRI for the Early Diagnosis of Parkinsonism in Patients with Diagnostic Uncertainty.

International clinical criteria are the reference for the diagnosis of degenerative parkinsonism in clinical research, but they may lack sensitivity and specificity in the early stages. To determine whether magnetic resonance imaging (MRI) analysis, through visual reading or machine-learning approaches, improves diagnostic accuracy compared with clinical diagnosis at an early stage in patients referred for suspected degenerative parkinsonism. Patients with initial diagnostic uncertainty between Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multisystem atrophy (MSA), with brain MRI performed at the initial visit (V1) and available 2-year follow-up (V2), were included. We evaluated the accuracy of the diagnosis established based on: (1) the international clinical diagnostic criteria for PD, PSP, and MSA at V1 ("Clin1"); (2) MRI visual reading blinded to the clinical diagnosis ("MRI"); (3) both MRI visual reading and clinical criteria at V1 ("MRI and Clin1"), and (4) a machine-learning algorithm ("Algorithm"). The gold standard diagnosis was established by expert consensus after a 2-year follow-up. We recruited 113 patients (53 with PD, 31 with PSP, and 29 with MSA). Considering the whole population, compared with clinical criteria at the initial visit ("Clin1": balanced accuracy, 66.2%), MRI visual reading showed a diagnostic gain of 14.3% ("MRI": 80.5%; P = 0.01), increasing to 19.2% when combined with the clinical diagnosis at the initial visit ("MRI and Clin1": 85.4%; P < 0.0001). The algorithm achieved a diagnostic gain of 9.9% ("Algorithm": 76.1%; P = 0.08). Our study shows the use of MRI analysis, whether by visual reading or machine-learning methods, for early differentiation of parkinsonism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The risk of Parkinson's disease in diabetic people: an updated systematic review and meta-analysis.

Diabetes mellitus (DM) and the risk of Parkinson's disease (PD) have been linked in previous studies. But the outcomes are still up for debate. This meta-analysis examined how DM affected the likelihood of developing PD. A comprehensive search of international databases, including Medline (PubMed), Web of Sciences, Scopus, and EMBASE until January 2023, was conducted to assess the relationship between DM and PD. Cohort and case-control studies were included. Subgroup analysis was carried out based on the duration of PD, continent, age, PD criteria, DM criteria, and effect size. In the meta-analysis, 25 studies encompassing a total of 39,209,316 participants were incorporated. The collective estimation of the relative risk concerning the association between Diabetes Mellitus (DM) and Parkinson's Disease (PD) yielded a value of 1.22 (95% CI 1.08-1.37). Subsequent subgroup analyses unveiled a heightened risk of DM among patients in the Asian demographic, particularly those of a younger age and a longer duration of PD. The findings from our comprehensive meta-analysis underscore a potentially emerging connection between DM and PD. These results showed that people with DM are more susceptible to developing other neurological diseases, such as PD, indicating that efforts are required to prevent the progression of such diseases among individuals with DM.

Validation of the Arabic version of Parkinson's Disease Sleep Scale-Revised Version (PDSS-2)

ObjectivesParkinson's disease sleep scale (PDSS) was recommended by the Movement Disorder Society task force for screening and grading the severity of sleep problems in Parkinson's disease (PD). This work aimed to examine the validity and reliability of an Arabic version of PDSS-2. MethodsThis cross-sectional study was carried out on 133 patients fulfilling diagnostic criteria for PD. The patients were clinically assessed using the following scales: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), modified Hoehn and Yahr Scale (H&Y), non-motor symptoms scale (NMSS), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI). PDSS-2 scale was translated according to approved translation standards into Arabic and back-translated into English. Patients were asked to respond based on their experience in the last week. ResultsThe mean PDSS2 score for the included PD patients was 17±10. Cronbach's α coefficient value was 0.89, indicating good internal consistency. Most items showed high item-total correlation; the lowest was 0.375, considered higher than the conventional cut-off of 0.3. Test-retest reliability showed good agreement (ICC: 0.848). The exploratory factor analysis showed that items had been loaded over four factors. Total PDSS-2 score was positively correlated to age, disease duration, modified H&Y scale, MDS-UPDRS, NMSS, BDI, and global PSQI score. A cut-off point of 13 could differentiate poor sleepers from good sleepers with 91% sensitivity and 70% specificity (AUC 0.893, P<0.001). ConclusionThe Arabic version of PDSS-2 has appropriate validity and can be reliably used for assessing sleep-related problems in Arabic-speaking patients with PD.

Comparison of different risk scores for Parkinson disease in a population-based 10-year study.

Different algorithms aiming to identify individuals at risk of Parkinson disease (PD) have been proposed. Comparative studies of these scores and their recent updates in the general elder population are needed. We have previously applied the "basic" PREDICT-PD algorithm, designed for remote screening, and the original and updated Movement Disorder Society (MDS) criteria for prodromal PD to the longitudinal population-based Bruneck study cohort. We have now additionally employed the "enhanced" PREDICT-PD algorithm (which includes motor assessment, olfaction, probable rapid eye movement sleep behaviour disorder status, pesticide exposure, and diabetes as additional factors). Risk scores were calculated based on comprehensive baseline assessments (2005) in 574 subjects aged 55-94 years (290 females), and cases of incident PD were identified at 5-year (n = 11) and 10-year follow-up (n = 9). We analysed the association of the different log-transformed risk scores with incident PD at follow-up (calculated per 1-SD unit change). The enhanced PREDICT-PD algorithm was associated with incident PD over 10-years of follow-up, yielding higher odds for incident PD (odds ratio [OR] = 4.61, 95% confidence interval [CI] = 2.68-7.93, p < 0.001) compared with the basic PREDICT-PD score (OR = 2.38, 95% CI = 1.49-3.79, p < 0.001). The updated MDS prodromal criteria yielded a numerically higher OR of 7.13 (95% CI = 3.49-14.54, p < 0.001) in comparison with the original criteria as well as the enhanced PREDICT-PD algorithm, with overlapping 95% CIs. The enhanced PREDICT-PD algorithm was significantly associated with incident PD. The consistent performance of both the enhanced PREDICT-PD algorithm and the updated MDS prodromal criteria compared to their original versions supports their use in PD risk screening.

Association of biallelic RFC1 expansion with early-onset Parkinson's disease.

The biallelic repeat expansion (AAGGG)exp in the replication factor C subunit 1 gene (RFC1) is a frequent cause of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) as well as late-onset ataxia. The clinical spectrum of RFC1 disease has expanded since the first identification of biallelic (AAGGG)exp and includes now various nonclassical phenotypes. Biallelic (AAGGG)exp in RFC1 in patients with clinically confirmed Parkinson's disease (PD) has recently been found. A nationwide cohort of 273 Finnish patients with early-onset PD was examined for the biallelic intronic expansion in RFC1. The expansion (AAGGG)exp was first screened using extra long polymerase chain reactions (Extra Large-PCRs) and flanking multiplex PCR. The presence of biallelic (AAGGG)exp was then confirmed by repeat-primed PCR and, finally, the repeat length was determined by long-read sequencing. Three patients were found with the biallelic (AAGGG)exp in RFC1 giving a frequency of 1.10% (0.23%-3.18%; 95% confidence interval). The three patients fulfilled the diagnostic criteria of PD, none of them had ataxia or neuropathy, and only one patient had a mild vestibular dysfunction. The age at onset of PD symptoms was 40-48 years and their disease course had been unremarkable apart from the early onset. Our results suggest that (AAGGG)exp in RFC1 is a rare cause of early-onset PD. Other populations should be examined in order to determine whether our findings are specific to the Finnish population.

Clinical Diagnostic Accuracy of Parkinson's Disease: Where Do We Stand?

Clinical diagnostic accuracy of Parkinson's disease (PD) remains suboptimal. Changes in disease concept may have improved clinical diagnostic accuracy in the past decade. However, current clinical diagnostic criteria have not been validated against neuropathological confirmation. This study aims to provide up-to-date clinical diagnostic accuracy data and validate current clinical diagnostic criteria for PD against neuropathology. A retrospective review of medical records of consecutive patients with parkinsonism from the Queen Square Brain Bank was performed between 2009 and 2019. Clinical diagnosis was documented at early (within 5 years of motor symptom onset) and final stages and categorized by movement disorder experts or regular clinicians. Movement Disorder Society Parkinson's disease (MDS-PD) diagnostic criteria were retrospectively applied. Diagnostic accuracy parameters (sensitivity, specificity, positive/negative predictive value, and accuracy) were calculated using neuropathological diagnosis as the gold standard. A total of 267 patients (141 PD and 126 non-PD parkinsonism) were included. Clinical diagnostic accuracy was 97.2% for experts, 92.5% for the MDS clinically probable PD criteria, and 90.3% for clinicians. Similar figures were obtained when applied at an early stage (91.5%, 89.5%, and 84.2% diagnostic accuracy, respectively). MDS clinically established early PD criteria demonstrated very high specificity (98.4%) at early stages. Our results showed an important improvement in PD clinical diagnostic accuracy in clinical practice over the past decade, more marked at early stages of the disease. MDS-PD diagnostic criteria is a valid tool in clinical practice and research for the identification of PD patients showing excellent sensitivity and specificity, although movement disorder experts' diagnosis remains the gold standard PD diagnosis during life. © 2023 International Parkinson and Movement Disorder Society.

Identification of DOT1L inhibitor in a screen for factors that promote dopaminergic neuron survival.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra region of the midbrain. Diagnostic criteria for PD require that at least two of three motor signs are observed: tremor, rigidity, and/or bradykinesia. The most common and effective treatment for PD is Levodopa (L-DOPA) which is readily converted to DA and has been the primary treatment since the 1960's. Dopamine agonists have also been developed but are less effective than L-DOPA. Although the lack of a model system to study PD has hampered efforts to identify treatments, diverse screening strategies have been proposed for identification of new pharmaceutical candidates. Here, we describe a pilot screen to identify candidate molecules from a bioactive compound library, that might increase formation, maintenance and/or survival of DA neurons in vitro. The screen used a previously characterized reporter construct consisting of the luciferase gene inserted downstream of the endogenous tyrosine hydroxylase (TH) gene and neurons differentiated from human pluripotent stem cells for 18 days. The reporter mimics expression of TH and includes a secreted luciferase whose activity can be measured non-invasively over multiple timepoints. Screening of the bioactive compound library resulted in the identification of a single molecule, SGC0946, that is an inhibitor of DOT1L (Disruptor Of Telomeric silencing 1-Like) which encodes a widely-conserved histone H3K79 methyltransferase that is able to both activate and repress gene transcription. Our results indicate that SGC0946 increased reporter luciferase activity with a single treatment for 48-h post-plating being equivalent to continuous treatment. Moreover, data suggested that the total number of neurons differentiated in the assays was comparable from experiment to experiment under different SGC0946 treatments over time. In contrast, data suggested that the survival and/or maintenance of DA neurons might be specifically enhanced by SGC0946 treatment. These results document the feasibility of a set of tools for further exploration of small molecules that may impact DA neuron differentiation, maintenance and/or survival. Results provide evidence in support of other reports that indicate inhibition of DOT1L may play an important role in maintenance and survival of neural progenitor cells (NPCs) and their lineage-specific differentiation.

Idiopathic rapid eye movement sleep behavior disorder in Japan: An observational study

IntroductionIdiopathic rapid eye movement sleep behavior disorder (iRBD) is one of the most specific prodromal symptoms of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy. The Japan Parkinson's Progression Markers Initiative (J-PPMI) was a prospective cohort study conducted in Japanese patients with iRBD to investigate biomarkers for prodromal synucleinopathies. We carried out an initial assessment of the J-PPMI study to reveal the factors correlated with dopamine transporter single-photon emission computed tomography (DaT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy. MethodsThis cross-sectional study was conducted in 108 patients with iRBD, selected from the J-PPMI study. We divided the patients into four groups based on the MIBG and DaT results. We also recorded the patients’ demographics and clinical data. Following PD probability calculation, we examined the biomarkers associated with DaT and MIBG. ResultsNinety-five of the enrolled patients (88%) met the diagnostic criteria for prodromal PD based on the probability score. Only five patients had normal MIBG and DaT. We identified 29 cases with decreased DaT and MIBG, all of whom met the above diagnostic criteria. Both DaT and MIBG were significantly correlated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. ConclusionBoth DaT and MIBG are important biomarkers for confirming synucleinopathies and/or staging disease progression. Although 95% of iRBD patients were consistent with the body-first subtype concept, alpha-synuclein pathologies of iRBD might have widespread systemic involvement rather than being confined to the lower brainstem, particularly in patients with reduced MoCA-J scores.

A Remote Longitudinal Observational Study of Individuals at Genetic Risk for Parkinson Disease: Baseline Results.

Background and ObjectivesTo recruit and characterize a national cohort of individuals who have a genetic variant (LRRK2 G2019S) that increases risk of Parkinson disease (PD), assess participant satisfaction with a decentralized, remote research model, and evaluate interest in future clinical trials.MethodsIn partnership with 23andMe, Inc., a personal genetics company, LRRK2 G2019S carriers with and without PD were recruited to participate in an ongoing 36-month decentralized, remote natural history study. We examined concordance between self-reported and clinician-determined PD diagnosis. We applied the Movement Disorder Society Prodromal Parkinson's Disease Criteria and asked investigators to identify concern for parkinsonism to distinguish participants with probable prodromal PD. We compared baseline characteristics of LRRK2 G2019S carriers with PD, with prodromal PD, and without PD.ResultsOver 15 months, we enrolled 277 LRRK2 G2019S carriers from 34 states. At baseline, 60 had self-reported PD (mean [SD] age 67.8 years [8.4], 98% White, 52% female, 80% Ashkenazi Jewish, and 67% with a family history of PD), and 217 did not (mean [SD] age 53.7 years [15.1], 95% White, 59% female, 73% Ashkenazi Jewish, and 57% with a family history of PD). Agreement between self-reported and clinician-determined PD status was excellent (κ = 0.94, 95% confidence interval 0.89–0.99). Twenty-four participants had prodromal PD; 9 met criteria for probable prodromal PD and investigators identified concern for parkinsonism in 20 cases. Compared with those without prodromal PD, participants with prodromal PD were older (63.9 years [9.0] vs 51.9 years [15.1], p < 0.001), had higher modified Movement Disorders Society-Unified Parkinson's Disease Rating Scale motor scores (5.7 [4.3] vs 0.8 [2.1], p < 0.001), and had higher Scale for Outcomes in PD for Autonomic Symptoms scores (11.5 [6.2] vs 6.9 [5.7], p = 0.002). Two-thirds of participants enrolled were new to research, 97% were satisfied with the overall study, and 94% of those without PD would participate in future preventive clinical trials.DiscussionAn entirely remote national cohort of LRRK2 G2019S carriers was recruited from a single site. This study will prospectively characterize a large LRRK2 G2019S cohort, refine a new model of clinical research, and engage new research participants willing to participate in future therapeutic trials.

Parkinson Disease: Epidemiology, Pathology, and Clinical Diagnosis

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. PD predominantly affects elderly people, and most countries are now facing a marked demographic change, with a progressively larger proportion of the population reaching old age. Thus, PD is expected to cause an increasing social and economic burden on society in the near future. The causes of PD are still mostly unknown. There has been a substantial progress in our understanding of the genetic basis of PD in the past 15 years; however, these mutations explain only a small fraction of all PD cases and other non-genetic factors may play a role. This review covers the epidemiology, pathology, and clinical diagnosis of PD. Figures show age-specific incidence of PD, age-specific prevalence of PD, PD risks for exposures reported in high-quality studies, PD and atypical parkinsonism clinical features, and neuroimaging alterations in PD and atypical parkinsonism. Tables list factors associated with increased or decreased risk of PD, Braak staging scheme of α-synuclein pathology in PD, United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic for PD, National Institute of Neurological Disorders and Stroke diagnostic criteria for PD, differential diagnosis of parkinsonian syndromes, and “atypical” atypical parkinsonism.

Parkinson Disease: Epidemiology, Pathology, and Clinical Diagnosis

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. PD predominantly affects elderly people, and most countries are now facing a marked demographic change, with a progressively larger proportion of the population reaching old age. Thus, PD is expected to cause an increasing social and economic burden on society in the near future. The causes of PD are still mostly unknown. There has been a substantial progress in our understanding of the genetic basis of PD in the past 15 years; however, these mutations explain only a small fraction of all PD cases and other non-genetic factors may play a role. This review covers the epidemiology, pathology, and clinical diagnosis of PD. Figures show age-specific incidence of PD, age-specific prevalence of PD, PD risks for exposures reported in high-quality studies, PD and atypical parkinsonism clinical features, and neuroimaging alterations in PD and atypical parkinsonism. Tables list factors associated with increased or decreased risk of PD, Braak staging scheme of α-synuclein pathology in PD, United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic for PD, National Institute of Neurological Disorders and Stroke diagnostic criteria for PD, differential diagnosis of parkinsonian syndromes, and “atypical” atypical parkinsonism.

Fist-Edge-Palm (FEP) test has a high sensitivity in differentiating dementia from normal cognition in Parkinson's disease

BackgroundThe Fist-Edge-Palm (FEP) test takes 0.5–3 min to complete and is highly sensitive in differentiating Alzheimer's disease and frontotemporal dementia from normal cognition, but it has not yet been studied in Parkinson's disease (PD). ObjectiveTo determine the sensitivity and specificity of the FEP test in screening patients with PD for cognitive impairment and dementia. MethodsPD patients were recruited and divided into three groups based on cognitive status: normal cognition, mild cognitive impairment (MCI) and dementia according to 2015 MDS clinical diagnostic criteria for PD and clinical dementia rating scale (CDR) assessment for cognitive status. MMSE, FEP and clock drawing test (CDT) were tested in all recruited PD patients. Chi-square test was used to compare the sensitivity of FEP and CDT in detecting PDD and PD-MCI. ResultsA total of 108 PD patients were included: 52 normal cognition, 28 MCI, and 28 dementia. The sensitivity of FEP in differentiating PDD from PD-NC was 96.4% and the sensitivity for PD-MCI from PD-NC was 71.4%. The sensitivity of CDT in differentiating PDD from PD-NC was 71.4% and PD-MCI from PD-NC was 53.6%. The sensitivities of FEP and CDT were 83.9% and 62.5%, respectively, in identifying cognitive impairment (CDR ≥ 0.5) in PD patients. ConclusionFEP is a sensitive screening tool in differentiating PDD or PD-MCI from PD-NC, and it is much faster than MMSE and more sensitive than CDT. FEP may be a practical screening tool for daily clinical practice.

High Prevalence of Early Parkinson's Disease in Patients With Subtle Parkinsonian Signs.

Background: Little is known about how frequently patients with a Unified Parkinson Disease Rating Scale part III (UPDRS-III) score of 3 or 4, including postural and action tremor, could be classified into early Parkinson's disease (PD).Objective: To examine the prevalence of early PD in patients with subtle parkinsonian signs (rest tremor, postural tremor, and rigidity) without bradykinesia, having a UPDRS-III score of 3 or 4.Methods: Parkinsonism was assessed using UPDRS-III based on both the United Kingdom PD Society Brain Bank criteria and the Movement Disorder Society PD criteria. Ninety patients with a UPDRS-III score of 3 or 4, including postural tremor, were evaluated by 123I-FP-CIT SPECT (DaTscan), brain MRI, the Mini-Mental State Examination, and smell test. Some patients were additionally examined by 123I-metaiodobenzylguanidine myocardial scintigraphy or 123I-N-isopropyl-p-iodoamphetamine SPECT.Results: Seventy-five [mean age (standard deviation): 76.9 (8.1)] out of 90 patients (83.3%) showed abnormal findings on DaTscan imaging: 57 out of 75 (76.0%) showed a reduced specific binding ratio (SBR) accompanied by an egg shape pattern (n = 37, 49.3%) or a mixed type pattern (n = 14, 18.7%), both reduced SBR and increased asymmetry index (AI) with a normal shape (n = 4, 5.3%), and reduced SBR only (n = 2, 2.7%); 18 (24.0%) showed an egg shape pattern or a mixed type pattern without reduced SBR. In other words, 69 out of 75 patients (92.0%) showed either an egg shape or a mixed type pattern with or without reduced SBR. All patients were free of dementia, and their olfactory function was significantly impaired compared with controls (n = 141) on the odor-stick identification test for Japanese (p < 0.0001).Conclusions: The prevalence of patients with subtle parkinsonian signs having a UPDRS-III score of 3 or 4, including postural tremor, is unexpectedly high in daily clinical practice, and most of these patients could be categorized into mild early-stage PD.

123I-Metaiodobenzylguanidine Myocardial Scintigraphy in Discriminating Degenerative Parkinsonisms.

ABSTRACTBackground 123I‐Metaiodobenzylguanidine (123I‐MIBG) myocardial scintigraphy is a useful technique to differentiate Parkinson's disease (PD) from atypical parkinsonisms, since it is generally abnormal in PD and normal in the latter. Reduction of myocardial MIBG uptake is a supportive feature in the latest PD diagnostic criteria.ObjectivesTo explore the clinical contribution of myocardial scintigraphy in discriminating different forms of parkinsonisms, especially when atypical features are present.MethodsForty‐one patients with parkinsonism underwent a 123I‐MIBG myocardial scintigraphy in our Movement Disorders Center. Disease evolution was reviewed by applying the latest disease criteria for PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as appropriate. Three diagnostic times were defined: T1 (before scintigraphy execution), T2 (immediately after the exam) and T3 (two years later). Early and delayed heart/mediastinum (H/M) ratios and washout rate (WR) were analyzed.ResultsMyocardial scintigraphy showed impaired MIBG uptake in 12 out of 15 patients with a definite PD diagnosis, while normal uptake was found in 20 of 26 patients with no‐PD. Early and delayed H/M ratios were significantly lower in PD compared to overall no‐PD patients and MSA patients. 123I‐MIBG myocardial scintigraphy was abnormal in all PD patients with dysautonomia. After 123I‐MIBG myocardial scintigraphy (T2), in 9 patients (22%) an improvement of diagnostic accuracy was reached.ConclusionsDiagnostic accuracy of myocardial scintigraphy in distinguishing PD from atypical parkinsonism was suboptimal. Nevertheless, this study confirmed the relevance of 123I‐MIBG myocardial scintigraphy for the discrimination of PD from atypical parkinsonism, especially when dysautonomic symptoms are present.

Prodromal Parkinson disease subtypes - key to understanding heterogeneity.

In Parkinson disease (PD), pathological processes and neurodegeneration begin long before the cardinal motor symptoms develop and enable clinical diagnosis. In this prodromal phase, risk and prodromal markers can be used to identify individuals who are likely to develop PD, as in the recently updated International Parkinson and Movement Disorders Society research criteria for prodromal PD. However, increasing evidence suggests that clinical and prodromal PD are heterogeneous, and can be classified into subtypes with different clinical manifestations, pathomechanisms and patterns of spatial and temporal progression in the CNS and PNS. Genetic, pathological and imaging markers, as well as motor and non-motor symptoms, might define prodromal subtypes of PD. Moreover, concomitant pathology or other factors, including amyloid-β and tau pathology, age and environmental factors, can cause variability in prodromal PD. Patients with REM sleep behaviour disorder (RBD) exhibit distinct patterns of α-synuclein pathology propagation and might indicate a body-first subtype rather than a brain-first subtype. Identification of prodromal PD subtypes and a full understanding of variability at this stage of the disease is crucial for early and accurate diagnosis and for targeting of neuroprotective interventions to ensure efficacy.

Late life psychotic features in prodromal Parkinson's disease

IntroductionSome case series have suggested that psychotic features could occur even before the onset of motor symptoms of Parkinson's Disease (PD). Our aim was to investigate a possible association between psychotic symptoms and prodromal Parkinson's disease in a population-based cohort, the Hellenic Longitudinal Investigation of Aging and Diet study. MethodsThis cross-sectional study included participants aged ≥65 years without dementia or PD. We defined psychotic symptoms as the presence of at least one new hallucinatory or delusional feature, assessed with the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer's Disease, exhibited only at follow-up and not present at baseline visit. We calculated the probability of prodromal PD (pPD) for every participant, according to the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD. ResultsParticipants who developed psychotic manifestations over a three-year follow up (20 of 914) had 1.3 times higher probability of pPD score (β [95%CI]: 1.3 [0.9-1.5], p=0.006) compared to non-psychotic subjects. This association was driven mostly by depressive symptoms, constipation and subthreshold parkinsonism (p<0.05). ConclusionOur data indicate that emerging psychotic features evolve in parallel with the probability of pPD. This is the first study that provides evidence for the presence of psychotic experiences in pPD. The association detected needs to be confirmed in longitudinal studies.

A study based on the embodied emotion approach: The recognition of whole‐body social emotions and postural control in Alzheimer's disease dementia, Parkinson's disease and healthy control

AbstractBackgroundAlzheimer's disease dementia (ADD) and Parkinson's disease (PD) have a significant impairment in social emotion recognition. Most of these studies assess emotional perception as the ability to identify others' facial emotions (Ekman faces). Nevertheless, emotional recognition with information that integrates whole‐body and postural control responses has not been investigated in ADD or PD.Method66 participants were recruited (ADD, PD, healthy controls (HC)). Subjects were diagnosed following NINCDS‐ADRDA criteria for ADD, and the United Kingdom Parkinson's Disease Society Brain Bank criteria for PD. Inclusion criteria considered older than 60 years and non‐other neuropsychiatric comorbidity. All participants were assessed in global cognition (ACE‐III), executive function (IFS, FAS), memory (FCRST), and social cognition (Minisea (Faux Pas (FP), Ekman faces (EF)). Three videos were elaborated with persons practicing risk sports (neutral, pleasant, unpleasant); and another unpleasant condition that did not show a human body (car accidents). Videos were previously validated by their emotional properties (120 subjects) following the Self‐assessment Manikin. Participants stood up at a force platform while videos (60 seconds) were presented at a TV screen (40 inches) at face height and 1 meter to the front. Postural control data to compute center of pressure (COP) were collected at a sample rate of 125Hz. At the end of each video, participants had to rate (1‐9) valence, intensity, and control. COP parameters included velocity, area, and frequency decomposition. Statistical analysis was performed on the first principal component (PC1) on those parameters. Emotional recognition was analyzed by ANOVA (3*3) (group*self‐perception), and postural data by Repeated‐Measures ANOVA (3*4) (group*emotional condition).ResultParticipants with ADD(n=25) show significant impairment in all cognitive domains assessed even when FP was adjusted for control questions, compared to PD(n=14) and HC(n=27). ADD showed significant differences in the recognition of whole‐body negative emotions (6,04+2,752), compared to PD (3,71+2,585) and HC (4,19+2,286). When postural control responses were analyzed, the pleasant condition showed significantly bigger displacements (PC1) than the other emotional conditions.ConclusionADD participants have problems recognizing negative social emotions that involve whole‐body. Emotional stimuli produce changes similar in postural control among groups, which depend on emotional conditions. These results suggest studying the emotion beyond facial emotion.

Corticospinal Tract Impairment of Patients With Parkinson's Disease: Triple Stimulation Technique Findings.

BackgroundCorticospinal tract impairment is no longer an absolute exclusion in the updated Movement Disorder Society Parkinson’s disease criteria. Triple stimulation technique (TST) is an accurate method to quantitatively assess the integrity and impairment of corticospinal pathway in a variety of neurological diseases. This study aims to evaluate the corticospinal tract impairment in Parkinson’s disease (PD) patients using TST.MethodsTen PD patients, 19 multiple-system atrophy parkinsonian variant (MSA-P) patients, and 12 healthy controls (HC) were sequentially recruited in this study. Information of age, disease duration, pyramidal signs, and Hoehn and Yahr (H&Y) stage was obtained from all patients. The TST was assessed at right abductor digiti minimi for HCs and both sides for patients. The Chi-square test was used for categorical variables, and variance analysis was performed for continuous variables in comparing the difference among PD, MSA-P, and HC, plus the post hoc tests for pairwise comparisons.ResultsAll subjects were age and gender matched. There was no significant difference in disease duration (p = 0.855), H-Y stage (p = 0.067), and the percentage of pyramidal signs present (p = 0.581) between MSA-P and PD patients. The mean TST ratio was 55.5 ± 32.2%, 81.7 ± 19.8%, and 96.8 ± 3.0% for PD, MSA-P, and HCs, correspondingly. PD patients had a significant lower TST amplitude ratio than MSA-P and HCs. The TST ratio of MSA-P was lower than HCs, but there was no significant difference (p = 0.160). Additionally, it was significantly higher in percentage of abnormal TST ratio between PD patients and MSA-P (p = 0.010).ConclusionCorticospinal tract impairment is not a rare manifestation in PD and can be quantitatively evaluated with TST. The result needs to be verified in amplified sample.