Showing papers in "Movement Disorders in 2022"
TL;DR: The second consensus criteria for the diagnosis of multiple system atrophy are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.
Abstract: The second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.
121 citations
51 citations
TL;DR: This update of the treatment guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society and the general neurologist should know the therapies and their place in the treatment pathway.
Abstract: This update of the treatment guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist should know the therapies and their place in the treatment pathway.
33 citations
TL;DR: In 2016, the International Parkinson and Movement Disorder Society Task Force for the Nomenclature of Genetic Movement Disorders presented a new system for naming genetically determined movement disorders and provided a criterion-based list of confirmed monogenic movement disorders as mentioned in this paper .
Abstract: In 2016, the Movement Disorder Society Task Force for the Nomenclature of Genetic Movement Disorders presented a new system for naming genetically determined movement disorders and provided a criterion‐based list of confirmed monogenic movement disorders. Since then, a substantial number of novel disease‐causing genes have been described, which warrant classification using this system. In addition, with this update, we further refined the system and propose dissolving the imaging‐based categories of Primary Familial Brain Calcification and Neurodegeneration with Brain Iron Accumulation and reclassifying these genetic conditions according to their predominant phenotype. We also introduce the novel category of Mixed Movement Disorders (MxMD), which includes conditions linked to multiple equally prominent movement disorder phenotypes. In this article, we present updated lists of newly confirmed monogenic causes of movement disorders. We found a total of 89 different newly identified genes that warrant a prefix based on our criteria; 6 genes for parkinsonism, 21 for dystonia, 38 for dominant and recessive ataxia, 5 for chorea, 7 for myoclonus, 13 for spastic paraplegia, 3 for paroxysmal movement disorders, and 6 for mixed movement disorder phenotypes; 10 genes were linked to combined phenotypes and have been assigned two new prefixes. The updated lists represent a resource for clinicians and researchers alike and they have also been published on the website of the Task Force for the Nomenclature of Genetic Movement Disorders on the homepage of the International Parkinson and Movement Disorder Society (https://www.movementdisorders.org/MDS/About/Committees--Other-Groups/MDS-Task-Forces/Task-Force-on-Nomenclature-in-Movement-Disorders.htm). © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
30 citations
TL;DR: Common genetic variance in apolipoprotein E (APOE), β‐glucocerebrosidase (GBA), microtubule‐associated protein tau (MAPT), and α‐synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results.
Abstract: Common genetic variance in apolipoprotein E (APOE), β‐glucocerebrosidase (GBA), microtubule‐associated protein tau (MAPT), and α‐synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results.
26 citations
TL;DR: An overview of the current knowledge, gaps, and possible strategies to deal with the unmet needs of women living with PD with a focus on the clinical and psychosocial aspects is provided.
Abstract: Personalized medicine considering sex, gender, and cultural context has become the vanguard of delivery of care. However, women's issues in Parkinson disease (PD), especially from a psychosocial standpoint, have been an overlooked field. The key research areas include women‐inclusive drug and device studies and genetic and hormonal considerations. Moreover, women with PD need to be educated and empowered on how to communicate their symptoms and needs, get engaged in research, get organized as a community, and support one another. Women with PD need tools to help track and convey their unique motor and nonmotor symptoms and psychological and social support needs. The management of PD needs to be customized to include the unique stages of women's lives, including menstrual cycles, pregnancy, perimenopause, menopause, and postmenopause. Specific guidelines for the use of hormonal treatments and customized dopamine replacement dosing need to be developed. Women need guidance on culturally sensitive wellness and self‐care strategies that are customized for them. Basic core competencies in knowledge for all clinicians treating women with PD need to be established, including how to accurately diagnose, proactively identify, and treat the symptoms of PD in women and to ensure timely referral for specialty care, advanced therapies, and research studies. Caregivers and families need guidance on holistically supporting women with PD. The voices of women living with PD must be amplified to catalyze real change in this neglected field. This paper provides an overview of the current knowledge, gaps, and possible strategies to deal with the unmet needs of women living with PD with a focus on the clinical and psychosocial aspects. © 2022 International Parkinson and Movement Disorder Society
25 citations
TL;DR: The role of α‐synuclein and β‐syn nuclein as potential biomarkers to improve the diagnostic characterization of synucleinopathies are discussed, thus highlighting their potential application in clinical trials for disease‐modifying therapies.
Abstract: The synuclein family includes three neuronal proteins, named α‐synuclein, β‐synuclein, and γ‐synuclein, that have peculiar structural features. α‐synuclein is largely known for being a key protein in the pathophysiology of Parkinson's disease (PD) and other synucleinopathies, namely, dementia with Lewy bodies and multisystem atrophy. The role of β‐synuclein and γ‐synuclein is less well understood in terms of physiological functions and potential contribution to human diseases. α‐synuclein has been investigated extensively in both cerebrospinal fluid (CSF) and blood as a potential biomarker for synucleinopathies. Recently, great attention has been also paid to β‐synuclein, whose CSF and blood levels seem to reflect synaptic damage and neurodegeneration independent of the presence of synucleinopathy. In this review, we aim to provide an overview on the pathophysiological roles of the synucleins. Because γ‐synuclein has been poorly investigated in the field of synucleinopathy and its pathophysiological roles are far from being clear, we focus on the interactions between α‐synuclein and β‐synuclein in PD. We also discuss the role of α‐synuclein and β‐synuclein as potential biomarkers to improve the diagnostic characterization of synucleinopathies, thus highlighting their potential application in clinical trials for disease‐modifying therapies. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
22 citations
TL;DR: Identification of the relationship between cognitive impairment and cholinergic innervation early in the disease will provide better insight into disease prognosis and possible early intervention.
Abstract: Altered cholinergic innervation plays a putative role in cognitive impairment in Parkinson's disease (PD) at least in advanced stages. Identification of the relationship between cognitive impairment and cholinergic innervation early in the disease will provide better insight into disease prognosis and possible early intervention.
19 citations
TL;DR: The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease patients and it has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers.
Abstract: The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers.
17 citations
TL;DR: Together with PTEN‐induced kinase 1, parkin regulates the clearance of dysfunctional mitochondria and was shown to prevent mitochondrial membrane permeability, impeding mitochondrial DNA escape and subsequent neuroinflammation.
Abstract: Mutations in the E3 ubiquitin ligase parkin cause autosomal recessive Parkinson's disease (PD). Together with PTEN‐induced kinase 1 (PINK1), parkin regulates the clearance of dysfunctional mitochondria. New mitochondria are generated through an interplay of nuclear‐ and mitochondrial‐encoded proteins, and recent studies suggest that parkin influences this process at both levels. In addition, parkin was shown to prevent mitochondrial membrane permeability, impeding mitochondrial DNA (mtDNA) escape and subsequent neuroinflammation. However, parkin's regulatory roles independent of mitophagy are not well described in patient‐derived neurons.
17 citations
TL;DR: Sirolimus (rapamycin) is an mTOR inhibitor that promotes α‐synuclein autophagy and reduces its associated neurotoxicity in preclinical models.
Abstract: Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α‐synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α‐synuclein autophagy and reduces its associated neurotoxicity in preclinical models.
TL;DR: Aggregation of α‐synuclein (oligomeric β‐syn) has been considered as the pathological hallmark of Parkinson's disease and multiple system atrophy and studies showed oligomericα‐syn/total α‐ syn ratio was increased in the saliva of patients with PD, suggesting that seeding activity of salivary oligomerics may be a novel biomarker for the diagnosis of PD.
Abstract: Aggregation of α‐synuclein (oligomeric α‐syn) has been considered as the pathological hallmark of Parkinson's disease (PD) and multiple system atrophy (MSA). Studies showed oligomeric α‐syn/total α‐syn ratio was increased in the saliva of patients with PD, suggesting that seeding activity of salivary oligomeric α‐syn may be a novel biomarker for the diagnosis of PD and MSA.
TL;DR: Air pollution is an emerging risk factor in the development of Parkinson's disease and a better understanding of how environmental exposures influence the pathogenesis of neurodegeneration is essential for reducing the incidence of disease and finding disease‐modifying therapies.
Abstract: Parkinson's disease, as well as other neurodegenerative disorders, are primarily characterized by pathological accumulation of proteins, inflammation, and neuron loss. Although there are some known genetic risk factors, most cases cannot be explained by genetics alone. Therefore, it is important to determine the environmental factors that confer risk and the mechanisms by which they act. Recent epidemiological studies have found that exposure to air pollution is associated with an increased risk for development of Parkinson's disease, although not all results are uniform. The variability between these studies is likely due to differences in what components of air pollution are measured, timing and methods used to determine exposures, and correction for other variables. There are several potential mechanisms by which air pollution could act to increase the risk for development of Parkinson's disease, including direct neuronal toxicity, induction of systemic inflammation leading to central nervous system inflammation, and alterations in gut physiology and the microbiome. Taken together, air pollution is an emerging risk factor in the development of Parkinson's disease. A number of potential mechanisms have been implicated by which it promotes neuropathology providing biological plausibility, and these mechanisms are likely relevant to the development of other neurodegenerative disorders such as Alzheimer's disease. This field is in its early stages, but a better understanding of how environmental exposures influence the pathogenesis of neurodegeneration is essential for reducing the incidence of disease and finding disease‐modifying therapies. © 2022 International Parkinson and Movement Disorder Society
TL;DR: To date, variants in the GBA gene represent the most frequent large‐effect genetic factor associated with Parkinson's disease (PD), however, the reason why individuals with the same GBA variant may or may not develop neurodegeneration and PD is still unclear.
Abstract: To date, variants in the GBA gene represent the most frequent large‐effect genetic factor associated with Parkinson's disease (PD). However, the reason why individuals with the same GBA variant may or may not develop neurodegeneration and PD is still unclear.
TL;DR: In this paper , the authors used magnetic resonance imaging (MRI) to localize structural disintegration in the locus coeruleus (LC) and its association with nonmotor dysfunction in Parkinson's disease.
Abstract: Parkinson's disease (PD) causes a loss of neuromelanin-positive, noradrenergic neurons in the locus coeruleus (LC), which has been implicated in nonmotor dysfunction.We used "neuromelanin sensitive" magnetic resonance imaging (MRI) to localize structural disintegration in the LC and its association with nonmotor dysfunction in PD.A total of 42 patients with PD and 24 age-matched healthy volunteers underwent magnetization transfer weighted (MTw) MRI of the LC. The contrast-to-noise ratio of the MTw signal (CNRMTw ) was used as an index of structural LC integrity. We performed slicewise and voxelwise analyses to map spatial patterns of structural disintegration, complemented by principal component analysis (PCA). We also tested for correlations between regional CNRMTw and severity of nonmotor symptoms.Mean CNRMTw of the right LC was reduced in patients relative to controls. Voxelwise and slicewise analyses showed that the attenuation of CNRMTw was confined to the right mid-caudal LC and linked regional CNRMTw to nonmotor symptoms. CNRMTw attenuation in the left mid-caudal LC was associated with the orthostatic drop in systolic blood pressure, whereas CNRMTw attenuation in the caudal most portion of right LC correlated with apathy ratings. PCA identified a bilateral component that was more weakly expressed in patients. This component was characterized by a gradient in CNRMTw along the rostro-caudal and dorso-ventral axes of the nucleus. The individual expression score of this component reflected the overall severity of nonmotor symptoms.A spatially heterogeneous disintegration of LC in PD may determine the individual expression of specific nonmotor symptoms such as orthostatic dysregulation or apathy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
TL;DR: This research presents a novel and scalable approach called “on-the-shelf” “cell reprograming” that allows for real-time characterization of the “spiking” in the immune system of Alzheimer’s disease.
Abstract: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany Department of Neurology, University Hospital Bonn, Bonn, Germany Houston Methodist Research Institute and Weil Cornell Medical College at Houston Methodist, Houston, Texas, USA McGill University, Montreal, Quebec, Canada Biogen, Cambridge, Massachusetts, USA Sorbonne Université, Paris Brain Institute, Paris Brain Institute – ICM, INSERM, CNRS, APHP, University Hospital de la Pitié-Salpêtrière Paris, Paris, France Departments of Neurology and Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA Ataxia UK, London, United Kingdom National Ataxia Foundation, Minneapolis, Minnesota, USA Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Xiangya Hospital, Central South University, Changsha, China Brain Research Institute, Niigata University, Niigata, Japan Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, São Paulo, Brazil National Yang-Ming Chiao Tung University, Taipei, Taiwan Taipei Neurologic Institute, Taipei Medical University, Taipei, Taiwan University of Melbourne, Parkville, Victoria, Australia Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany Center for Rare Diseases, University Hospital Tübingen, Tübingen, Germany Division Translational Genomics of Neurodegenerative Diseases, Center for Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
TL;DR: To determine if prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism, a non-lesion inducing dose of the parkinsonian toxin MPTP was administered to mice to induce mild to moderate disease and subsequent neuroinflammation and SNpc dopaminergic neuron loss was determined.
Abstract: Background Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses following SARS-CoV-2 infection with those observed after pandemic influenza, there is a question if a similar syndrome of post-encephalic parkinsonism could follow COVID-19 infection. Objectives To determine if prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. Methods hACE2 mice were infected with SARS-CoV-2 to induce mild to moderate disease. After 31 days recovery, mice were administered a non-lesion inducing dose of the parkinsonian toxin MPTP. Subsequent neuroinflammation and SNpc dopaminergic neuron loss was determined and compared to SARS-CoV-2 or MPTP alone. Results hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss following MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc dopaminergic neurons than SARS-CoV-2 or MPTP, respectively (p□<□0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in the SARS-CoV-2 + MPTP group compared to SARS-CoV-2 or MPTP alone. Conclusions Our observations have important implications for long-term public health, given the number of people that have survived SARS-CoV-2 infection as well as for future public policy regarding infection mitigation. However, it will be critical to determine if other agents known to increase risk of PD also have synergistic effects with SARS-CoV-2 and if are abrogated by vaccination. Funding This work was supported by grant from the State of North Carolina (PS, JE, DOR, RJS) and R21 NS122280 (RJS).
TL;DR: Agents targeting the metabotropic glutamate receptor 4 have emerged as a potentially attractive new class of drugs for the treatment of Parkinson's disease.
Abstract: Agents targeting the metabotropic glutamate receptor 4 have emerged as a potentially attractive new class of drugs for the treatment of Parkinson's disease (PD).
TL;DR: Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints that capture change in ataxia severity in patients' real life.
Abstract: Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints that capture change in ataxia severity in patients' real life.
TL;DR: Gut function should be taken into consideration when conducting microbial‐metabolite research, as SCFAs produced by gut microbiota are reduced in feces but paradoxically increased in plasma of patients with Parkinson's disease.
Abstract: Short‐chain fatty acids (SCFAs) produced by gut microbiota are reduced in feces but paradoxically increased in plasma of patients with Parkinson's disease (PD), which may stem from intestinal wall leakage. Gut function should be taken into consideration when conducting microbial‐metabolite research.
TL;DR: In this article , the influence of Type 2 diabetes on aspects of disease progression in Parkinson's was investigated, and the effects of comorbid T2DM on PD progression and quality of life by comparing symptom severity scores assessing a range of motor and nonmotor symptoms.
Abstract: Type 2 diabetes (T2DM) is an established risk factor for developing Parkinson's disease (PD), but its effect on disease progression is not well understood.The aim of this study was to investigate the influence of T2DM on aspects of disease progression in PD.We analyzed data from the Tracking Parkinson's study to examine the effects of comorbid T2DM on PD progression and quality of life by comparing symptom severity scores assessing a range of motor and nonmotor symptoms.We identified 167 (8.7%) patients with PD and T2DM (PD + T2DM) and 1763 (91.3%) patients with PD without T2DM (PD). After controlling for confounders, patients with T2DM had more severe motor symptoms, as assessed by Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (25.8 [0.9] vs. 22.5 [0.3] P = 0.002), and nonmotor symptoms, as assessed by Non-Motor Symptoms Scale total (38.4 [2.5] vs. 31.8 [0.7] P < 0.001), and were significantly more likely to report loss of independence (odds ratio, 2.08; 95% confidence interval [CI]: 1.34-3.25; P = 0.001) and depression (odds ratio, 1.62; CI: 1.10-2.39; P = 0.015). Furthermore, over time, patients with T2DM had significantly faster motor symptom progression (P = 0.012), developed worse mood symptoms (P = 0.041), and were more likely to develop substantial gait impairment (hazard ratio, 1.55; CI: 1.07-2.23; P = 0.020) and mild cognitive impairment (hazard ratio, 1.7; CI: 1.24-2.51; P = 0.002) compared with the PD group.In the largest study to date, T2DM is associated with faster disease progression in Parkinson's, highlighting an interaction between these two diseases. Because it is a potentially modifiable metabolic state, with multiple peripheral and central targets for intervention, it may represent a target for alleviating parkinsonian symptoms and slowing progression to disability and dementia. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
TL;DR: Human genetics research lacks diversity; over 80% of genome‐wide association studies have been conducted on individuals of European ancestry, limiting insights regarding disease mechanisms and creating disparities preventing equitable implementation of personalized medicine.
Abstract: Human genetics research lacks diversity; over 80% of genome‐wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine.
TL;DR: Diabetes is associated with incidence and prevalence of Parkinson's disease (PD) and glycated hemoglobin (HbA1c) levels have been linked with motor function and progression.
Abstract: Diabetes is associated with incidence and prevalence of Parkinson's disease (PD). Furthermore, glycated hemoglobin (HbA1c) levels have been linked with motor function and progression.
TL;DR: MOXIe was a two-part study evaluating the safety and efficacy of omaveloxolone in patients with Friedreich's ataxia, a rare, progressive neurological disease with no proven therapy as discussed by the authors .
Abstract: MOXIe was a two‐part study evaluating the safety and efficacy of omaveloxolone in patients with Friedreich's ataxia, a rare, progressive neurological disease with no proven therapy. MOXIe part 2, a randomized double‐blind placebo‐controlled trial, showed omaveloxolone significantly improved modified Friedreich's Ataxia Rating Scale (mFARS) scores relative to placebo. Patients who completed part 1 or 2 were eligible to receive omaveloxolone in an open‐label extension study.
TL;DR: A neurobiological framework of cost‐benefit decision making is applied to the problems of apathy and impulsivity in Huntington's disease and a mechanistic model is developed that elucidates the occurrence of these behavioral disturbances and points to potential treatment strategies and crucial research priorities.
Abstract: A caregiver's all‐too‐familiar narrative ‐ “He doesn't think through what he does, but mostly he does nothing.” Apathy and impulsivity, debilitating and poorly understood, commonly co‐occur in Huntington's disease (HD). HD is a neurodegenerative disease with manifestations bridging clinical neurology and psychiatry. In addition to movement and cognitive symptoms, neurobehavioral disturbances, particularly apathy and impulsivity, are prevalent features of HD, occurring early in the disease course, often worsening with disease progression, and substantially reducing quality of life. Treatments remain limited, in part because of limited mechanistic understanding of these behavioral disturbances. However, emerging work within the field of decision‐making neuroscience and beyond points to common neurobiological mechanisms underpinning these seemingly disparate problems. These insights bridge the gap between underlying disease pathology and clinical phenotype, offering new treatment strategies, novel behavioral and physiological biomarkers of HD, and deeper understanding of human behavior. In this review, we apply the neurobiological framework of cost‐benefit decision making to the problems of apathy and impulsivity in HD. Through this decision‐making lens, we develop a mechanistic model that elucidates the occurrence of these behavioral disturbances and points to potential treatment strategies and crucial research priorities. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
TL;DR: Replacement of the lysosomal enzyme glucocerebrosidase slows neurodegeneration in PD models and may be a promising disease‐modifying therapy in patients with PD, but recombinant GCase has limited penetration through the blood–brain barrier (BBB).
Abstract: GBA1 mutation is the most common genetic risk factor for Parkinson's disease (PD). Replacement of the lysosomal enzyme glucocerebrosidase (GCase) slows neurodegeneration in PD models and may be a promising disease‐modifying therapy in patients with PD. However, recombinant GCase has limited penetration through the blood–brain barrier (BBB). Microbubble‐mediated magnetic resonance–guided focused ultrasound (MRgFUS) can reversibly disrupt the BBB for drug delivery.
TL;DR: Higher nigral iron has been reported in Parkinson's disease (PD) and further research is needed to determine the cause.
Abstract: Higher nigral iron has been reported in Parkinson's disease (PD).
TL;DR: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early‐onset epileptic encephalopathy and/or chorea.
Abstract: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early‐onset epileptic encephalopathy and/or chorea.
TL;DR: TMS‐evoked electroencephalographic activity may unveil broader motor cortical network changes in PD as well as assess M1 excitability using transcranial magnetic stimulation.
Abstract: Motor impairment in Parkinson's disease (PD) reflects changes in the basal ganglia‐thalamocortical circuit converging on the primary motor cortex (M1) and supplementary motor area (SMA). Previous studies assessed M1 excitability in PD using transcranial magnetic stimulation (TMS)‐evoked electromyographic activity. TMS‐evoked electroencephalographic activity may unveil broader motor cortical network changes in PD.
TL;DR: In this article , the authors highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men, but it is unclear whether this association is causal or explained by reverse causation or confounding.
Abstract: Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding.