Identifying New Subtypes of Multiple System Atrophy Using Cluster Analysis.

Background: Multiple system atrophy (MSA) is a disease with diverse symptoms and the commonly used classifications, MSA-P and MSA-C, do not cover all the different symptoms seen in MSA patients. Additionally, these classifications do not provide information about how the disease progresses over time or the expected outcome for patients. Objective: To explore clinical subtypes of MSA with a natural disease course through a data-driven approach to assist in the diagnosis and treatment of MSA. Methods: We followed 122 cases of MSA collected from 3 hospitals for 3 years. Demographic characteristics, age of onset, clinical signs, scale assessment scores, and auxiliary examination were collected. Age at onset; time from onset to assisted ambulation; and UMSARS I, II, and IV, COMPASS-31, ICARS, and UPDRS III scores were selected as clustering elements. K-means, partitioning around medoids, and self-organizing maps were used to analyze the clusters. Results: The results of all three clustering methods supported the classification of three MSA subtypes: The aggressive progression subtype (MSA-AP), characterized by mid-to-late onset, rapid progression and severe clinical symptoms; the typical subtype (MSA-T), characterized by mid-to-late onset, moderate progression and moderate severity of clinical symptoms; and the early-onset slow progression subtype (MSA-ESP), characterized by early-to-mid onset, slow progression and mild clinical symptoms. Conclusions: We divided MSA into three subtypes and summarized the characteristics of each subtype. According to the clustering results, MSA patients were divided into three completely different types according to the severity of symptoms, the speed of disease progression, and the age of onset.

Detecting Abnormal Eye Movements in Patients with Neurodegenerative Diseases - Current Insights.

This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD), Parkinson's Disease (PD), atypical parkinsonism, and others, leveraging advancements in eye-tracking technology for enhanced diagnostic precision. We delve into the different classes of eye movements, their clinical assessment, and specific abnormalities manifesting in these diseases, highlighting the nuanced differences and shared patterns. For instance, AD and ADRD are characterized by increased saccadic latencies and instability in fixation, while PD features saccadic hypometria and mild smooth pursuit impairments. Atypical parkinsonism, notably Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), presents with distinct ocular motor signatures such as vertical supranuclear gaze palsy and saccadic apraxia, respectively. Our review underscores the diagnostic value of eye movement analysis in differentiating between these disorders and also posits the existence of underlying common pathological mechanisms. We discuss how eye movements have potential as biomarkers for neurodegenerative diseases but also some of the existing limitations.

Freezing of gait in idiopathic normal pressure hydrocephalus.

BACKGROUND: Reports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study's objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG's responsiveness to shunt surgery. METHODS: Videotaped standardized gait protocols with iNPH patients pre- and post-shunt surgery (n = 139; median age 75 (71-79) years; 48 women) were evaluated for FoG episodes by two observers (Cohens kappa = 0.9, p < 0.001). FoG episodes were categorized. Mini-mental state examination (MMSE) and MRI white matter hyperintensities (WMH) assessment using the Fazekas scale were performed. CSF was analyzed for Beta-amyloid, Tau, and Phospho-tau. Patients with and without FoG were compared. RESULTS: Twenty-two patients (16%) displayed FoG at baseline, decreasing to seven (8%) after CSF shunt surgery (p = 0.039). The symptom was most frequently exhibited during turning (n = 16, 73%). Patients displaying FoG were older (77.5 vs. 74.6 years; p = 0.029), had a slower walking speed (0.59 vs. 0.89 m/s; p < 0.001), a lower Tinetti POMA score (6.8 vs. 10.8; p < 0.001), lower MMSE score (21.3 vs. 24.0; p = 0.031), and longer disease duration (4.2 vs. 2.3 years; p < 0.001) compared to patients not displaying FoG. WMH or CSF biomarkers did not differ between the groups. CONCLUSIONS: FoG is occurring frequently in iNPH patients and may be considered a typical feature of iNPH. FoG in iNPH was associated with higher age, longer disease duration, worse cognitive function, and a more unstable gait. Shunt surgery seems to improve the symptom.

Brazilian dance self-perceived impacts on quality of life of people with Parkinson's.

Background: Parkinson's disease (PD) causes several motor and non-motor symptoms, resulting in negative impacts on physical, mental, emotional, and social aspects of people with PD quality of life. Dance has been considered as a potential non-pharmacological intervention to improve people with PD motor and non-motor symptoms, thereby enhancing quality of life. Purpose: To analyze the self-perceive impacts of Brazilian Dance on the quality of life (physical, mental, emotional, and social) of PwPD, both before and during the COVID-19 pandemic. Methods: Fourteen participants from the "Dança & Parkinson" project were included in this qualitative study. Data collection instruments consisted of a profile and personal data sheet; assessment of accessibility to the online dance classes; Telephone Montreal Cognitive Assessment by phone call; and semi-structured interview conducted through ZOOM video call. The participants characterization data were calculated using mean, standard deviation, and percentages with the Excel Program version 2013. Qualitative data was analyzed using the Thematic Analysis technique in the Nvivo, version 8.0, qualitative analysis of text, sound, and video program. Results: The participants reported facing various challenges in dealing with PD, which negatively impact their quality of life. However, their resilience, acceptance, and dedication to treatment play an important role in coping with the issues related to the disease. Brazilian dance, both in-person before the COVID-19 pandemic and online during the pandemic, led the participants to perceive improvements in physical, mental, emotional, and social aspects of quality of life. Conclusion: The Brazilian dance appears to have a positive impact on the physical, mental, emotional, and social aspects of the participants' quality of life, both before and during the COVID-19 pandemic.

Genetic testing for non-parkinsonian movement disorders: Navigating the diagnostic maze.

Genetic testing has become a valuable diagnostic tool for movement disorders due to substantial advancements in understanding their genetic basis. However, the heterogeneity of movement disorders poses a significant challenge, with many genes implicated in different subtypes. This paper aims to provide a neurologist's perspective on approaching patients with hereditary hyperkinetic disorders with a focus on select forms of dystonia, paroxysmal dyskinesia, chorea, and ataxia. Age at onset, initial symptoms, and their severity, as well as the presence of any concurrent neurological and non-neurological features, contribute to the individual clinical profiles of hereditary non-parkinsonian movement disorders, aiding in the selection of appropriate genetic testing strategies. There are also more specific diagnostic clues that may facilitate the decision-making process and may be highly specific for certain conditions, such as diurnal fluctuations and l-dopa response in dopa-responsive dystonia, and triggering factors, duration and frequency of attacks in paroxysmal dyskinesia. While the genetic and mutational spectrum across non-parkinsonian movement disorders is broad, certain groups of diseases tend to be associated with specific types of pathogenic variants, such as repeat expansions in many of the ataxias. Some of these pathogenic variants cannot be detected by standard methods, such as panel or exome sequencing, but require the investigation of intronic regions for repeat expansions, such as Friedreich's or FGF14-linked ataxia. With our advancing knowledge of the genetic underpinnings of movement disorders, the incorporation of precise and personalized diagnostic strategies can enhance patient care, prognosis, and the application and development of targeted therapeutic interventions.

Dysphagia Prevalence in Progressive Supranuclear Palsy: A Systematic Review and Meta-Analysis.

The objective of this systematic review was to determine the prevalence of dysphagia and aspiration in people with progressive supranuclear palsy (PSP). A search of six electronic databases was performed from inception to April 2022. No context restrictions were set. All primary research comprising figures to derive a prevalence rate were included. Two independent reviewers screened search results. Data were extracted by one reviewer. Conflicts were resolved by discussion with a third reviewer. The quality of included studies was assessed using the JBI Checklist for Prevalence Studies. From 877 studies, 12 were eligible for inclusion. Dysphagia had to be confirmed using instrumental assessments, clinical swallowing evaluation, screening, and patient-reported outcome measures (PROM). A random-effects meta-analysis calculated a pooled dysphagia prevalence in 78-89% (95% CI [60.6, 89.1], [78.9, 95.0]). depending on the chosen assessment method, and a pooled aspiration prevalence of 23.5% (95% CI [14.5, 33.7]). The included studies were of moderate quality, with high risk of selection and coverage bias and low to moderate risk of measurement bias. Dysphagia is highly prevalent in a sample of participants with mostly moderately severe PSP. Aspiration occurs in a quarter of this sample and is likely to increase as the disease progresses. Given the low general prevalence of PSP, studies remain at high risk for selection bias. Prospective research should focus on the development of dysphagia in the course of PSP and its subcategories using instrumental assessment and consider all phases of swallowing. REGISTRATION: The protocol of this systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) in April 2021 (registration number: CRD42021245204).

Under-Diagnosis of Dementia with Lewy Bodies in Individuals Racialized as Black: Hypotheses Regarding Potential Contributors.

Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias after Alzheimer's disease (AD) dementia. DLB is under-diagnosed across populations but may be particularly missed in older Black adults. The object of this review was to examine key features of DLB and potential associations with race in order to hypothesize why DLB may be under-diagnosed in Black adults in the U.S. In terms of dementia, symptoms associated with high rates of co-pathology (e.g., AD, vascular disease) in older Black adults may obscure the clinical picture that might suggest Lewy body pathology. Research also suggests that clinicians may be predisposed to give AD dementia diagnoses to Black adults, potentially missing contributions of Lewy body pathology. Hallucinations in Black adults may be misattributed to AD or primary psychiatric disease rather than Lewy body pathology. Research on the prevalence of REM sleep behavior in diverse populations is lacking, but REM sleep behavior disorder could be under-diagnosed in Black adults due to sleep patterns or reporting by caregivers who are not bed partners. Recognition of parkinsonism could be reduced in Black adults due to clinician biases, cultural effects on self-report, and potentially underlying differences in the frequency of parkinsonism. These considerations are superimposed on structural and systemic contributions to health (e.g., socioeconomic status, education, structural racism) and individual-level social exposures (e.g., social interactions, discrimination). Improving DLB recognition in Black adults will require research to investigate reasons for diagnostic disparities and education to increase identification of core symptoms in this population.

Differentiating progressive supranuclear palsy from other movement disorders using transcranial sonography: a systematic review and meta-analysis.

Progressive supranuclear palsy (PSP) is an atypical parkinsonism that presents with different phenotypes. There are still no validated diagnostic biomarkers for early diagnosis of PSP. Transcranial sonography (TCS) is a promising tool in the differential diagnosis of parkinsonian disorders; however, there are no systematic investigations about the application of TCS in PSP patients. Therefore, we performed a systematic review and meta-analysis to discuss the role of TCS in diagnosing PSP by systematically searching PubMed, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang databases. Of 66 obtained records, 16 articles, including 366 patients with PSP, were included. Our results showed the estimated random-effects pooled prevalence of substantia nigra hyperechogenicity in patients with PSP was 22% (95% CI 12-32%), lenticular nucleus hyperechogenicity was 70% (95% CI 52-82%), and enlarged third ventricle was 71% (95% CI 55-85%). Additionally, a normal echogenicity substantia nigra in TCS showed 70% sensitivity (95% CI 56-81%) and 86% specificity (95% CI 75-86%) to differentiate PSP from Parkinson's disease. In conclusion, TCS is an important supplementary biomarker for diagnosing PSP. At the same time, the diagnostic value of TCS in discriminating PSP from other atypical parkinsonism and between different PSP phenotypes needs further exploration.

Management of lower urinary tract symptoms in Parkinsonian disorders.

INTRODUCTION: The aim of the study was to present a narrative review of the literature on the management of lower urinary tract symptoms (LUTS) in patients presenting Parkinsonian disorders (PD). MATERIAL AND METHODS: We carried out a literature search in PubMed and Embase database, without time restriction. We used keywords and free-text words around "Parkinsonian disorders" AND "lower urinary tracts symptoms" without language restriction. We focused mainly on papers less than 10 years old. We included all studies evaluating LUTS in patients with PD. RESULTS: For the diagnostic management, authors emphasized the importance of differentiating Parkinson's disease with symptoms of bladder overactivity from multiple system atrophy with symptoms of bladder hypoactivity. Urodynamic evaluation was noted as the key element of diagnostic management. The therapeutic management proposed was symptomatic, based on functional urology techniques for the treatment of LUTS, both with drugs (especially anticholinergics) or surgery (intradetrusor injections of botulinum toxin, neuromodulation). Moreover, it was pointed out that it is always necessary to take into account the existence of a possible associated uropathy (prostate adenoma or pelvic prolapse). CONCLUSION: Urodynamic evaluation is the cornerstone of diagnostic management of LUTS in patients with PD. Therapeutic management is above all symptomatic and must be done in a collegial way involving the urologist, neurologist, gynecologist, and physical medicine and rehabilitation physician.

Corneal confocal microscopy demonstrates varying degrees of neurodegeneration in atypical parkinsonian disorders.

OBJECTIVE: We have used corneal confocal microscopy (CCM) to identify corneal nerve loss as a potential marker of neurodegeneration in participants with Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). METHODS: Patients with PD (n = 19), PSP (n = 11), MSA (n = 8) and healthy controls (n = 18) underwent neurological assessment and CCM. RESULTS: Corneal nerve fibre density was significantly lower in participants with PD (p = 0.005), PSP (p = 0.005) and MSA (p = 0.0003) compared to controls. Corneal nerve branch density was significantly lower in participants with PD (p = 0.01) and MSA (p = 0.019), but not in participants with PSP (p = 0.662), compared to controls. Corneal nerve fibre length was significantly lower in participants with PD (p = 0.002) and MSA (p = 0.001) but not in participants with PSP (p = 0.191) compared to controls. CONCLUSION: CCM detects corneal nerve loss in participants with PD and MSA and to a lesser extent in PSP compared to healthy controls.

Sustained attention in mild cognitive impairment with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer's disease (MCI-AD), and any performance deficits which emerged with sustained effort. METHOD: We included longitudinal data on a CPT sustained attention task for 89 participants with MCI-LB or MCI-AD and 31 healthy controls, estimating ex-Gaussian response time parameters, omission and commission errors. Performance trajectories were estimated both cross-sectionally (intra-task progress from start to end) and longitudinally (change in performance over years). RESULTS: While response times in successful trials were broadly similar, with slight slowing associated with clinical parkinsonism, those with MCI-LB made considerably more errors. Omission errors were more common throughout the task in MCI-LB than MCI-AD (OR 2.3, 95% CI: 1.1-4.7), while commission errors became more common after several minutes of sustained attention. Within MCI-LB, omission errors were more common in those with clinical parkinsonism (OR 1.9, 95% CI: 1.3-2.9) or cognitive fluctuations (OR 4.3, 95% CI: 2.2-8.8). CONCLUSIONS: Sustained attention deficits in MCI-LB may emerge in the form of attentional lapses leading to omissions, and a breakdown in inhibitory control leading to commission errors.

Autonomic dysregulation during sleep in Parkinsonian spectrum disorders - A proof of concept.

INTRODUCTION: Autonomic dysfunction is common in α-synucleinopathies such as Lewy Body dementias (LBD), Parkinson's disease (PD), and isolated REM Sleep Behavior Disorder (iRBD). We analyzed pulse-rate changes during sleep to index autonomic nervous system (ANS) dysfunction in patients with α-synucleinopathies vs. non-synucleinopathy groups expected to have normal ANS function. METHODS: Patients with LBD (n = 16), PD (PD, n = 14) or iRBD (n = 12) were compared to the non-synucleinopathy groups Alzheimers disease dementia (ADem, n = 26), mild cognitive impairment (MCI, n = 34) or controls (CG, n = 54). Sleep Profiler was used to derive a sleep autonomic activation index (AAI), i.e., ≥6 beat-per-minute increase/decrease, pulse rate coefficient of variation (PR-CV), and automated sleep staging with sleep-spindles and non-REM hypertonia (NRH). Analysis included statistical group comparisons and receiver operating characteristics curves to determine optimal classification of groups. RESULTS: AAI and PR-CV were moderately correlated across all recordings (rs = 0.58, P < 0.0001), except in the LBD and PD groups. AAI but not PR-CV differentiated the LBD, PD and iRBD from non-Parkinsonian groups. AAI was decreased in LBD and PD patients compared to the CG (p < 0.003) and MCI (p < 0.03). AAI decreased based on age and its receiver operating characteristic area under the curve ranged from 0.63 to 0.75. AAI had a weak negative correlation to NRH (rs ≤ -0.26) but not sleep-spindles. CONCLUSION: Synucleinopathy-related ANS dysfunction can reasonably discriminate prodromal and manifest PD/LBD diseased groups from non-synucleinopathies. Further studies incorporating AAI into a multivariate classifier of neurodegenerative disorders based on sleep characteristics acquired in the patient's home are planned.

Movement disorders in hereditary spastic paraplegias / Distúrbios de movimento em paraplegia espástica hereditária

Abstract Background Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia. Objective To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases. Methods We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022. Results Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia. Conclusion Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

Resumo Antecedentes As paraplegias espásticas hereditárias ou familiares (SPG) compreendem um grupo de doenças geneticamente e fenotipicamente heterogêneas caracterizadas por degeneração progressiva dos tratos corticospinais. As formas complicadas evoluem com vários outros sinais e sintomas neurológicos, incluindo distúrbios do movimento e ataxia. Objetivo Resumir as descrições clínicas de SPG que se manifestam com distúrbios do movimento ou ataxias para auxiliar o clínico na tarefa de diagnosticar essas doenças. Métodos Realizamos uma revisão da literatura, incluindo relatos de casos, séries de casos, artigos de revisão e estudos observacionais publicados em inglês até dezembro de 2022. Resultados O parkinsonismo juvenil ou de início precoce com resposta variável à levodopa foi relatado principalmente em SPG7 e SPG11. A distonia pode ser observada em pacientes com SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 e SPG76. O tremor não é um achado frequente em pacientes com SPG, mas é descrito em diferentes tipos de SPG, incluindo SPG7, SPG9, SPG11, SPG15 e SPG76. A mioclonia é raramente descrita em SPG, afetando pacientes com SPG4, SPG7, SPG35, SPG48 e SPOAN (paraplegia espástica, atrofia óptica e neuropatia). SPG4, SPG6, SPG10, SPG27, SPG30 e SPG31 podem raramente apresentar ataxia com atrofia cerebelar. E SPG autossômico recessivo, como SPG7 e SPG11, também pode apresentar ataxia. Conclusão Indivíduos com SPG podem apresentar diferentes formas de distúrbios do movimento, como parkinsonismo, distonia, tremor, mioclonia e ataxia. O distúrbio específico do movimento na manifestação clínica de um paciente com SPG pode ser uma pista clínica para o diagnóstico.

Parkinson's Neuropathology Puzzle: A Systematic Review Uncovering the Pathological Culprits Behind the Neurological Disease.

Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives all over the world, Parkinson's disease (PD) has never failed to attract a formidable interest from the vast majority of neurologists and researchers worldwide. This review article will analyze the pathophysiology, etiology, genetics, and pathological stages of Parkinson's disease with their corresponding clinical sequels. A review article was conducted using research databases including PubMed, PubMed Central, Springer, and Elsevier. The research articles reviewed using databases were written in English, German, Japanese, and Chinese and published within the preceding 50 years. Based on the article's findings, we concluded that Parkinson's disease is a progressive disorder with a variety of motor and non-motor symptoms that are influenced by a cascade of pathological neuronal abnormalities such as Lewy neurites and Lewy bodies that gradually build up with an eventual consequence of neurodegeneration of dopamine-secreting neurons. Multiple genetic mutations, pathophysiological events, and environmental factors act as the foundation to initiate that cascade.

Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson's disease.

BACKGROUND: There is a need for biomarkers to support an accurate diagnosis of Parkinson's disease (PD). Cerebrospinal fluid (CSF) has been a successful biofluid for finding neurodegenerative biomarkers, and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies. Using a large-scale multiplex proximity extension assay (PEA) approach, we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders (APD). METHODS: CSF from patients with PD, corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), multiple system atrophy and controls, were analysed with Olink PEA panels. Three cohorts were used in this study, comprising 192, 88 and 36 cases, respectively. All samples were run on the Cardiovascular II, Oncology II and Metabolism PEA panels. RESULTS: Our analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts, respectively, compared to controls. Among them, 6 proteins were changed in both cohorts. Midkine (MK) was increased in PD with the strongest effect size and results were validated with ELISA. Another most increased protein in PD, DOPA decarboxylase (DDC), which catalyses the decarboxylation of DOPA (L-3,4-dihydroxyphenylalanine) to dopamine, was strongly correlated with dopaminergic treatment. Moreover, Kallikrein 10 was specifically changed in APD compared with both PD and controls, but unchanged between PD and controls. Wnt inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent cohorts. CONCLUSIONS: Using the large-scale PEA approach, we have identified potential novel PD diagnostic biomarkers, most notably MK and DDC, in the CSF of PD patients.

Burden of Parkinsonism and Parkinson's Disease on Health Service Use and Outcomes in Latin America.

BACKGROUND: Little is known about the burden of parkinsonism and Parkinson's disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. OBJECTIVE: The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. METHODS: 12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis. RESULTS: At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries. CONCLUSIONS: Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services.

The prevalence of sarcopenia in Parkinson's disease and related disorders- a systematic review.

BACKGROUND: The prevalence of sarcopenia (reduced skeletal muscle strength and mass), Parkinson's disease (PD) and Parkinson's related disorders (PRD) all increase with age. They also share risk factors and pathogenetic features. An increased prevalence of sarcopenia in PD and PRD than the general population was thus postulated. METHODS: Four databases were searched using predefined literature search strategies. Studies conducted in participants with PD or PRD reporting the prevalence of sarcopenia and those providing data to compute the prevalence were included. Pre-sarcopenia, probable/possible sarcopenia and confirmed sarcopenia were defined according to the main sarcopenia working groups. Risk of bias was assessed using the AXIS tool. RESULTS: 1978 studies were identified; 97 assessed in full; 14 met inclusion criteria. The median study quality score was 15/20. The range of probable sarcopenia was 23.9 to 66.7%, and it did not change after excluding PRD participants. The prevalence of confirmed sarcopenia in participants with any parkinsonian disorder ranged from 2 to 31.4%. Including just PD participants, the range was 10.9 to 31.4%. In studies with controls, sarcopenia was more prevalent in PD and PRD. There was a positive non-significant trend between severity of motor symptoms and prevalence of sarcopenia or components of sarcopenia. High heterogeneity precluded meta-analysis, therefore there was insufficient evidence to conclude whether sarcopenia is more prevalent in PD or PRD. CONCLUSIONS: Probable and confirmed sarcopenia are common in PD and PRD and they may be associated with disease severity. This co-occurrence supports the value of screening for sarcopenia in parkinsonian populations.

α-Synuclein seed amplification assay as a diagnostic tool for parkinsonian disorders.

INTRODUCTION: Synucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example, atypical parkinsonisms like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Seed amplification assays (SAA), developed for the detection of α-synuclein (αSyn) aggregates in CSF, have been successful when used as a biomarker evaluation for synucleinopathies. In this study, we investigated the potential of this assay to not only detect αSyn seeds in CSF, but also discriminate between movement disorders. METHODS: The αSyn-SAA was tested in a Scandinavian cohort composed of 129 CSF samples from patients with PD (n = 55), MSA (n = 27), CBD (n = 7), and PSP (n = 16), as well as healthy controls (HC, n = 24). RESULTS: The αSyn seed amplification assay (αSyn-SAA) was able to correctly identify all PD samples as positive (sensitivity of 100%) while also discriminating the PD group from HC (70.8% specificity, p < 0.0001) and tauopathies [CBD (71% specificity) and PSP (75% specificity), p < 0.0001)]. The αSyn-SAA was also able to identify almost all MSA samples as positive for αSyn aggregation (sensitivity of 92.6%). In general, this assay is able to discriminate between the synucleinopathies and tauopathies analyzed herein (p < 0.0001) despite the overlapping symptoms in these diseases. CONCLUSION: These findings suggest the αSyn-SAA is a useful diagnostic tool for differentiating between different parkinsonian disorders, although further optimization may be needed.

Striatal dopamine transporter uptake, parkinsonism and cognition in Alzheimer's disease.

BACKGROUND AND PURPOSE: The correlates of motor parkinsonism in Alzheimer's disease (AD) remain controversial. The effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD were evaluated. METHODS: This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography, 18 F-florbetaben positron emission tomography, 3 T brain magnetic resonance imaging, and Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen and substantia nigra were quantified. The relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score and cognition was investigated using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates. RESULTS: Path analysis and multivariable GLMs for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness. CONCLUSIONS: Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.

Large-scale activation likelihood estimation meta-analysis of parkinsonian disorders.

Parkinsonism is a feature of several neurodegenerative disorders, including Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy. Neuroimaging studies have yielded insights into parkinsonian disorders; however, due to variability in results, the brain regions consistently implicated in these disorders remain to be characterized. The aim of this meta-analysis was to identify consistent brain abnormalities in individual parkinsonian disorders (Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy) and to investigate any shared abnormalities across disorders. A total of 44 591 studies were systematically screened following searches of two databases. A series of whole-brain activation likelihood estimation meta-analyses were performed on 132 neuroimaging studies (69 Parkinson's disease; 23 progressive supranuclear palsy; 17 corticobasal syndrome; and 23 multiple system atrophy) utilizing anatomical MRI, perfusion or metabolism PET and single-photon emission computed tomography. Meta-analyses were performed in each parkinsonian disorder within each imaging modality, as well as across all included disorders. Results in progressive supranuclear palsy and multiple system atrophy aligned with current imaging markers for diagnosis, encompassing the midbrain, and brainstem and putamen, respectively. PET imaging studies of patients with Parkinson's disease most consistently reported abnormality of the middle temporal gyrus. No significant clusters were identified in corticobasal syndrome. When examining abnormalities shared across all four disorders, the caudate was consistently reported in MRI studies, whilst the thalamus, inferior frontal gyrus and middle temporal gyri were commonly implicated by PET. To our knowledge, this is the largest meta-analysis of neuroimaging studies in parkinsonian disorders and the first to characterize brain regions implicated across parkinsonian disorders.