Incidence Of Parkinson's Disease Research Articles

COVID-19 and neurological disorders: what might connect Parkinson's disease to SARS-CoV-2 infection.

SARS-CoV-2 infection leading to Coronavirus disease 19 (COVID-19) rapidly became a worldwide health emergency due to its elevated infecting capacity, morbidity, and mortality. Parkinson’s disease (PD) is the second most common neurodegenerative disorder and, nowadays the relationship between SARS-CoV-2 outbreak and PD reached a great interest. Apparently independent one from the other, both diseases share some pathogenetic and clinical features. The relationship between SARS-CoV-2 infection and PD is complex and it depends on the direction of the association that is which of the two diseases comes first. Some evidence suggests that SARS-CoV-2 infection might be a possible risk factor for PD wherein the exposure to SARS-CoV-2 increase the risk for PD. This perspective comes out from the increasing cases of parkinsonism following COVID-19 and also from the anatomical structures affected in both COVID-19 and early PD such as olfactory bulb and gastrointestinal tract resulting in the same symptoms such as hyposmia and constipation. Furthermore, there are many reported cases of patients who developed hypokinetic extrapyramidal syndrome following SARS-CoV-2 infection although these would resemble a post-encephalitic conditions and there are to date relevant data to support the hypothesis that SARS-CoV-2 infection is a risk factor for the development of PD. Future large, longitudinal and population-based studies are needed to better assess whether the risk of developing PD after COVID-19 exists given the short time span from the starting of pandemic. Indeed, this brief time-window does not allow the precise estimation of the incidence and prevalence of PD after pandemic when compared with pre-pandemic era. If the association between SARS-CoV-2 infection and PD pathogenesis is actually putative, on the other hand, vulnerable PD patients may have a greater risk to develop COVID-19 being also more prone to develop a more aggressive disease course. Furthermore, PD patients with PD showed a worsening of motor and non-motor symptoms during COVID-19 outbreak due to both infection and social restriction. As well, the worries related to the risk of being infected should not be neglected. Here we summarize the current knowledge emerging about the epidemiological, pathogenetic and clinical relationship between SARS-CoV-2 infection and PD.

Association of Physical Activity and Parkinson Disease in Women: Long-term Follow-up of the E3N Cohort Study.

Previous cohort studies reported that a single measure of physical activity (PA) assessed at baseline was associated with lower Parkinson's disease (PD) incidence, but a meta-analysis suggested that this association was restricted to men. Due to the long prodromal phase of the disease, reverse causation could not be excluded as a potential explanation. Our objective was to study the association between time-varying PA and PD using lagged analyses to address the potential for reverse causation, and to compare PA trajectories in patients prior to diagnosis and matched controls. We used data from E3N (1990-2018), a cohort study of women affiliated with a national health insurance plan for persons working in education. PA was self-reported in six questionnaires over the follow-up. As questions changed across questionnaires, we created a time-varying latent PA (LPA) variable using latent-process mixed models. PD was ascertained using a multistep validation process based on medical records, or a validated algorithm based on drug claims. We set-up a nested case-control study to examine differences in LPA trajectories using multivariable linear mixed models with a retrospective time scale. Cox proportional hazards models with age as the timescale and adjusted for confounders were used to estimate the association between time-varying LPA and PD incidence. Our main analysis used a 10y-lag to account for reverse causation; sensitivity analyses used 5y, 15y, and 20y-lags. Analyses of trajectories (1,196 cases, 23,879 controls) showed that LPA was significantly lower in cases than in controls throughout the follow-up, including 29y before diagnosis; the difference between cases and controls started to increase ∼10y before diagnosis (P-interaction=0.003). In our main survival analysis, of 95,354 women free of PD in 2000, 1,074 women developed PD over a mean follow-up of 17.2y. PD incidence decreased with increasing LPA (P-trend=0.001), with 25% lower incidence in those in the highest quartile compared to the lowest (adjusted hazard ratio=0.75, 95% confidence interval=0.63-0.89). Using longer lags yielded similar conclusions. Higher PA level is associated with lower PD incidence in women, not explained by reverse causation. These results are important for planning interventions for PD prevention.

Conversion Rate of Essential Tremor to Essential Tremor Parkinson Disease: Data From a Prospective Longitudinal Study.

There has been a long-standing dialog as to whether essential tremor (ET) increases the risk of developing Parkinson disease (PD). While there are relevant cross-sectional data, there are almost no longitudinal prospective data. We quantified the conversion rate from ET to ETPD in a prospective longitudinal cohort study of patients with ET. We compared the observed rate with that reported in the epidemiologic literature. We enrolled patients with ET in a prospective, longitudinal study. A senior movement disorders neurologist evaluated standardized neurologic examinations every 18 months. One hundred ninety-three patients with ET (mean age = 78.1 ± 9.6 years, range = 55-96) had a mean follow-up duration of 4.1 years. Seven (3.6%) converted from ET to ETPD. The incidence of PD among patients with ET was 7/792.9 person-years (py; i.e., 882.8/100,000 py). A meta-analysis of the incidence (per 100,000 py) of PD in 14 studies from 13 countries across 4 continents reported an incidence of PD = 61.21 (men, 40 years or older) and 37.55 (women, 40 years or older). The incidence/100,000 py in men peaked in the 80- to 89-year-old age group (258.47) and in women in the 80- to 89-year-old age group (103.48 py). The abovementioned published values are 3.4-23.5 times lower than the value we observed for ET. The incidence of PD in an ET cohort is substantially higher than that reported in historical population-based control groups across numerous countries. Additional prospective longitudinal data are needed to further explore this association.

The Endotoxin Hypothesis of Parkinson's Disease.

The endotoxin hypothesis of Parkinson's disease (PD) is the idea that lipopolysaccharide (LPS) endotoxins contribute to the pathogenesis of this disorder. LPS endotoxins are found in, and released from, the outer membrane of Gram-negative bacteria, for example in the gut. It is proposed that gut dysfunction in early PD leads to elevated LPS levels in the gut wall and blood, which promotes both α-synuclein aggregation in the enteric neurons and a peripheral inflammatory response. Communication to the brain via circulating LPS and cytokines in the blood and/or the gut-brain axis leads to neuroinflammation and spreading of α-synuclein pathology, exacerbating neurodegeneration in brainstem nuclei and loss of dopaminergic neurons in the substantia nigra, and manifesting in the clinical symptoms of PD. The evidence supporting this hypothesis includes: (1) gut dysfunction, permeability, and bacterial changes occur early in PD, (2) serum levels of LPS are increased in a proportion of PD patients, (3) LPS induces α-synuclein expression, aggregation, and neurotoxicity, (4) LPS causes activation of peripheral monocytes leading to inflammatory cytokine production, and (5) blood LPS causes brain inflammation and specific loss of midbrain dopaminergic neurons, mediated by microglia. If the hypothesis is correct, then treatment options might include: (1) changing the gut microbiome, (2) reducing gut permeability, (3) reducing circulating LPS levels, or (4) blocking the response of immune cells and microglia to LPS. However, the hypothesis has a number of limitations and requires further testing, in particular whether reducing LPS levels can reduce PD incidence, progression, or severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Factors Associated with Parkinsons Disease and the Current Treatment on PD

Parkinsons disease (PD) is neurodegenerative disease that occur in 1% of people in their sixth and subsequent decades. The classical of PD symptoms include of tremors, bradykinesia, muscle stiffness, and loss of balance, and are associated by the reduced function of degenerative neurons and intracellular accumulation of abnormal proteins. The exact causation of PD is unknown, with environmental and genetic factors showing relation to PD. Genetic mutations and environmental toxicants, such as pesticides, are related with an elevated incidence of PD, according to epidemiologic research. Several investigations carried in animal models confirmed this association. Currently no treatment can retard or halt the disease progression, including the most commonly used therapy which is the replenishment of striatal dopamine through oral administration. This do alleviate most of the symptoms, but it also introduces several side effects including dyskinesias. At present, gene therapy is not used in the treatment of PD; rather, it is only employed in disease trials. The non-disease modifying treatments have been showing encouraging results while the disease modifying treatments hold a greater potential.

Bidirectional association between Parkinson's disease and obstructive sleep apnea: a cohort study.

Chronic intermittent hypoxia due to obstructive sleep apnea (OSA) causes oxidative stress, which may contribute to the pathophysiology of Parkinson's disease (PD). However, the bidirectional relationship between PD and OSA has not been satisfactorily established. The objective of this study was to try to estimate whether there is a bidirectional relationship between PD and OSA through a retrospective cohort study in the South Korean population. This study used data from the Korean National Health Information Database of the National Health Insurance Service, which contains data from 3.5 million individuals evenly distributed. In study 1, patients with OSA were matched in a 1:2 ratio with non-OSA controls. In study 2, patients with PD were matched in a 1:2 ratio with non-PD controls. A stratified Cox proportional hazards model was used to calculate hazard ratios. In study 1, which included 6,396 patients with OSA and 12,792 non-OSA controls, the incidence of PD per 10,000 person-years was 11.59 in the OSA group and 8.46 in the non-OSA group. The OSA group demonstrated a 1.54-fold higher incidence of PD than the non-OSA group (95% confidence interval, 1.14-2.07; P < .05). In study 2, which included 3,427 patients with PD and 6,854 non-PD controls, the incidence of OSA per 10,000 person-years was 14.97 in the PD group and 7.72 in the non-PD group. The PD group demonstrated a 1.92-fold higher incidence of OSA than the non-PD group (95% confidence interval, 1.32-2.78; P < .05). This study supports a possible bidirectional relationship between PD and OSA. Jeon S-H, Hwang YS, Oh S-Y, etal. Bidirectional association between Parkinson's disease and obstructive sleep apnea: a cohort study. J Clin Sleep Med. 2023;19(9):1615-1623.

Treatment of High Blood Pressure is associated with a Reduced Incidence of Parkinson’s disease (S42.007)

<h3>Objective:</h3> We performed an agnostic drug-wide association study (DWAS) in Norway estimating the association between all drugs prescribed in Norway and the subsequent incidence of Parkinson’s disease (PD). <h3>Background:</h3> Several drugs including treatments for cardiovascular diseases have been associated with a reduced incidence of PD. <h3>Design/Methods:</h3> We employed data on drug use in the entire Norwegian population from 2004 to 2019 (4.6 million) registered in the Norwegian Prescription Registry, including more than 600 million individual prescriptions. Drug classes were screened according to ATC codes at level 2, corresponding to therapeutic subgroups. Individuals who developed PD during the 15 years of follow-up (n=15,849) were identified using an algorithm based on drugs prescribed to treat the disease. Cox regression models with exposure as time-dependent variable were specified, and all p-values were corrected for multiple testing using the false discovery rate. <h3>Results:</h3> We found several novel associations between drug classes and the incidence of PD including a <i>decreased</i> incidence of PD among users of drugs acting on the renin-angiotensin system (0.86, 95%CI: 0.83–0.89). We also found an inverse association between calcium channel blockers and PD incidence, but we could not confirm the previously reported association between lipid-modifying agents and PD. Further, beta blocking agents and drugs for cardiac therapy were associated with an <i>increased</i> PD incidence. We also found increased PD incidence for drugs used in the treatment of prodromal symptoms of PD, including urologicals, drugs for constipation, anti-psychotics, and antidepressants. <h3>Conclusions:</h3> We observed two large drug classes of anti-hypertensives being associated with a subsequent reduced incidence of PD. The finding of two other cardiovascular drug classes being associated with an <i>increased</i> PD incidence calls for more detailed epidemiological studies and experimental studies to elucidate possible mechanisms. <b>Disclosure:</b> Trond Riise has nothing to disclose. Mr. Solheim has nothing to disclose. The institution of Dr. Bjornevik has received research support from Michael J. Fox Foundation. The institution of Dr. Bjornevik has received research support from National Multiple Sclerosis Society. The institution of Dr. Bjornevik has received research support from Department of Defense. Dr. Igland has nothing to disclose. Miss Tuominen has nothing to disclose. Dr. Abolpour Mofrad has nothing to disclose. Dr. Cortese has received personal compensation in the range of $500-$4,999 for serving as a speaker at educational event with Roche. Dr. Scherzer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Scherzer has received research support from NIH. The institution of Dr. Scherzer has received research support from Michael J. Fox Foundation. The institution of Dr. Scherzer has received research support from American Parkinson’s Disease Association. Dr. Scherzer has received intellectual property interests from a discovery or technology relating to health care. Mrs. Romanowska has nothing to disclose.

Voiding Dysfunction Due to Urethral Sphincter Dysfunction Might Be an Early Neurological Presentation of Central Nervous System Disorders in Aged Patients.

To investigate the incidence of central nervous system (CNS) diseases in adult patients with voiding dysfunction and videourodynamics (VUDS) proven urethral sphincter dysfunction. This retrospective analysis reviewed the medical charts of patients aged > 60 years who underwent VUDS for non-prostatic voiding dysfunction from 2006 to 2021. A chart review was performed to search for the occurrence and treatment of CNS diseases after the VUDS examination up to 2022. The diagnosis of CNS disease, such as cerebrovascular accidents (CVA), Parkinson's disease (PD), and dementia, by neurologists was also retrieved from the charts. Based on the VUDS findings, patients were divided into the following subgroups: dysfunctional voiding (DV), poor relaxation of the external sphincter (PRES), and hypersensitive bladder (HSB) and coordinated sphincter subgroups. The incidence of CVA, PD, and dementia in each subgroup was recorded and compared among them using one-way analysis of variance (ANOVA). A total of 306 patients were included. VUDS examinations revealed DV in 87 patients, PRES in 108, and HSB in 111. Among them, 36 (11.8%) patients had CNS disease, including CVA in 23 (7.5%), PD in 4 (1.3%), and dementia in 9 (2.9%). Among the three subgroups, the DV group had the highest incidence rate of CNS disease (n = 16, 18.4%), followed by PRES (n = 12, 11.1%) and HSB (n = 8, 7.2%). However, no significant difference was noted in the incidence of CNS disease across the three subgroups. Nevertheless, the incidence of CNS disease was higher in patients with DV and PRES than that in the general population. The incidence of CNS diseases was high in patients aged > 60 years with voiding dysfunction due to urethral sphincter dysfunction. Patients with VUDS-confirmed DV had the highest incidence of CNS disease among the three subgroups.

Association between Inflammatory Bowel Disease and Subsequent Development of Restless Legs Syndrome and Parkinson's Disease: A Retrospective Cohort Study of 35,988 Primary Care Patients in Germany.

In addition to the gastrointestinal symptoms, inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is associated with extraintestinal manifestations, including neurological disorders, which are gaining increasing attention due to a recently increased focus on the gut-brain axis. Here we aim to evaluate the association between IBD and restless legs syndrome (RLS) as well as Parkinson's disease (PD) in a cohort of primary care patients in Germany. The study included 17,994 individuals with a diagnosis of IBD (7544 with CD and 10,450 with UC) and 17,994 propensity-score-matched individuals without IBD from the Disease Analyzer database (IQVIA). An initial diagnosis of RLS or PD was assessed as a function of IBD. Associations between CD and UC with RLS and PD were analyzed using Cox regression models. During the 10-year observation period, 3.6% of CD patients vs. 1.9% of matched non-IBD pairs (p < 0.001) and 3.2% of UC patients vs. 2.7% of matched pairs (p < 0.001) were diagnosed with RLS. The results were confirmed by Cox regression analysis, which showed a significant association between UC (HR: 1.26; 95% CI: 1.02-1.55) and CD (HR: 1.60; 95% CI: 1.23-2.09) and subsequent RLS. The incidence of PD in IBD patients was not significantly increased. However, we observed a non-significant trend towards a higher incidence of PD in male patients with CD but not UC (HR: 1.55; 95%CI: 0.98-2.45, p = 0.064). The present analysis suggests a significant association between IBD and the subsequent development of RLS. These findings should stimulate further pathophysiological research and may eventually lead to specific screening measures in patients with IBD.

β2-Adrenoreceptor Agonists, Montelukast, and Parkinson Disease Risk.

This study was undertaken to examine the association between montelukast use, β2-adrenoreceptor (β2AR) agonist use, and later Parkinson disease (PD). We ascertained use of β2AR agonists (430,885 individuals) and montelukast (23,315 individuals) from July 1, 2005 to June 30, 2007, and followed 5,186,886 PD-free individuals from July 1, 2007 to December 31, 2013 for incident PD diagnosis. We estimated hazard ratios and 95% confidence intervals using Cox regressions. We observed 16,383 PD cases during on average 6.1 years of follow-up. Overall, use of β2AR agonists and montelukast were not related to PD incidence. A 38% lower PD incidence was noted among high-dose montelukast users when restricted to PD registered as the primary diagnosis. Overall, our data do not support inverse associations between β2AR agonists, montelukast, and PD. The prospect of lower PD incidence with high-dose montelukast exposure warrants further investigation, especially with adjustment for high-quality data on smoking. ANN NEUROL 2023;93:1023-1028.

Parkinson's disease population-wide registries in the United States: Current and future opportunities.

Parkinson's disease (PD) is a neurodegenerative disease with both genetic and environmental risk factors. Efforts to understand the growing incidence and prevalence of PD have led to several state PD registry initiatives in the United States. The California PD Registry (CPDR) is the largest state-wide PD registry and requires electronic reporting of all eligible cases by all medical providers. We borrow from our experience with the CPDR to highlight 4 gaps to population-based PD registries. Specifically we address (1) who should be included in PD registries; (2) what data should be collected in PD case reports; (3) how to ensure the validity of case reports; and (4) how can state PD registries exchange and aggregate information. We propose a set of recommendations that addresses these and other gaps toward achieving a promise of a practical, interoperable, and scalable PD registry in the U.S., which can serve as a key health information resource to support epidemiology, health equity, quality improvement, and research.

Long-Term Intake of Folate, Vitamin B6, and Vitamin B12 and the Incidence of Parkinson's Disease in a Sample of U.S. Women and Men.

Folate and vitamins B6 and B12 have been proposed as protective against the development of Parkinson's disease (PD). Two prior longitudinal studies were inconclusive. The aim was to examine the association of long-term intake of folate, vitamin B6, and vitamin B12 with the incidence of PD. The study population comprised 80,965 women (Nurses' Health Study, 1984-2016) and 48,837 men (Health Professionals Follow-up Study, 1986-2016) followed prospectively for the development of PD. Intake of B vitamins was measured at baseline and every 4 years thereafter using food frequency questionnaires. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of PD based on quintiles of cumulative average intake adjusting for potential confounders. Secondary analyses considered different lagged exposure periods as well as baseline and recent intakes. In separate analyses of cumulative average intake, total folate, B6, and B12 were not associated with the risk of PD. Results from 8-, 12-, and 16-year lag analyses were consistent with these findings. Results for baseline intake of folate and B6 also pointed toward a null association. In contrast, a lower PD risk was observed among individuals with higher baseline total intake of B12 (pooled HR top vs. bottom quintile: 0.80; 95% CI: 0.67-0.95; P-trend=0.01); results from 20-year lag analyses were consistent with this finding. Our results do not support the hypothesis that a higher intake of folate or vitamin B6 would reduce PD risk in this population. Our results provide moderate support for a possible protective effect of vitamin B12 on the development of PD. © 2023 International Parkinson and Movement Disorder Society.

Association between Antiepileptic Drugs and Incident Parkinson’s Disease among Patients Followed in German Primary Care Practices

The aim of this study was to analyze whether prescriptions of antiepileptic drugs (AEDs) are significantly associated with an increased incidence of Parkinson's disease (PD) in the German population. This study used data from German primary care practices found in the Disease Analyzer database (IQVIA) and included all patients aged ≥18 years who were diagnosed with PD between January 2010 and December 2021 (index date). The controls were patients without PD matched (1:1) by age, sex, and pre-diagnostic observation time in years. Associations between AED prescriptions (any AED as well as separate evaluations for carbamazepine, lamotrigine, levetiracetam, sodium valproate, gabapentin, and pregabalin) and subsequent diagnosis of PD were examined using a logistic regression model adjusted for epilepsy, restless legs syndrome, and neuropathy diagnoses. We identified 24,950 cases that were matched with 24,950 controls (mean age 75.2 years, 47.3% women). Diagnoses of epilepsy, restless legs syndrome, and neuropathy as well as AED prescription were significantly associated with an increased incidence of PD. In the multivariate analysis, incidence of PD was significantly associated with epilepsy (OR: 1.91; 95% CI: 1.69-2.15), restless legs syndrome (OR: 3.02; 95% CI: 2.73-3.34), and neuropathy (OR: 1.53; 95% CI: 1.44-1.62)), as well as the prescription of any AED (OR: 1.43; 95% CI: 1.33-1.53), sodium valproate (OR: 2.39; 95% CI: 1.84-3.11), gabapentin (OR: 1.36; 95% CI: 1.22-1.52), and pregabalin (OR: 1.28; 95% CI: 1.15-1.41). Conclusion: Prescriptions of AEDs, including sodium valproate, gabapentin, and pregabalin, were associated with an increased risk of subsequent PD, even after adjustment for underlying diagnoses. Further studies are needed to confirm the present results.

Statin Use and Incidence of Parkinson's Disease in Women from the French E3N Cohort Study.

Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose-response relations based on time-varying exposures. We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. We used data from the E3N cohort study of French women (follow-up, 2004-2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins-PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54-79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR]=0.87, 95% confidence interval [CI]=0.67-1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR=0.70, 95% CI=0.51-0.98), with a dose-response relation for the mean daily dose (P-linear trend=0.02). There was no association for hydrophilic statins. Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose-response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Incidence of Parkinson's disease and modifiable risk factors in Korean population: A longitudinal follow-up study of a nationwide cohort.

We aimed to investigate the incidence of Parkinson's disease (PD) by age and year for each sex as well as the modifiable risk factors for PD. Using data from the Korean National Health Insurance Service, 938,635 PD and dementia-free participants aged ≥40 years who underwent general health examinations were followed to December 2019. We analyzed the PD incidence rates according to age, year and sex. To investigate the modifiable risk factors for PD, we used the Cox regression model. Additionally, we calculated the population-attributable fraction to measure the impact of the risk factors on PD. During follow-up, 9,924 of the 938,635 (1.1%) participants developed PD. The incidence of PD increased continuously from 2007 to 2018, reaching 1.34 per 1,000 person-years in 2018. The incidence of PD also increases with age, up to 80 y. Presence of hypertension (SHR = 1.09, 95% CI 1.05 to 1.14), diabetes (SHR = 1.24, 95% CI 1.17 to 1.31), dyslipidemia (SHR = 1.12, 95% CI 1.07 to 1.18), ischemic stroke (SHR = 1.26, 95% CI 1.17 to 1.36), hemorrhagic stroke (SHR = 1.26, 95% CI 1.08 to 1.47), ischemic heart disease (SHR = 1.09, 95% CI 1.02 to 1.17), depression (SHR = 1.61, 95% CI 1.53 to 1.69), osteoporosis (SHR = 1.24, 95% CI 1.18 to 1.30), and obesity (SHR = 1.06, 95% CI 1.01 to 1.10) were independently associated with a higher risk for PD. Our results highlight the effect of modifiable risk factors for PD in the Korean population, which will help establish health care policies to prevent the development of PD.

Dietary and Environmental Risk Factors in Parkinson's and Alzheimer's Disease: A Semi-Quantitative Pilot Study.

Environmental influence and dietary variations are well-known risk factors for various diseases including neurodegenerative disorders. Preliminary evidence suggests that diet in early-life and living environment might influence the incidence of Parkinson's disease (PD) in later phase of life. There have been limited epidemiologic studies on this aspect especially in India. In this hospital-based case-control study, we intended to identify dietary and environmental risk factors of PD. Patients with PD (n = 105), Alzheimer's disease (AD) (n = 53) and healthy individuals (n = 81) were recruited. Dietary intake and environmental exposures were assessed using a validated Food-Frequency and Environmental Hazard Questionnaire. Their demographic details and living environment were also recorded using the same questionnaire. Pre-morbid consumption of carbohydrate and fat was significantly higher whereas dietary fiber and fruit content was significantly lesser in PD as compared to AD and healthy age-matched controls. Meat and milk intake was the highest among all the food groups in PD patients. Rural living and their habitation near water bodies were significantly more frequent in PD patients. We found that past intake of carbohydrate, fat, milk, and meat are associated with increased risk of PD. On the other hand, rural living and habitat near water bodies might be associated with incidence and severity of PD. Hence, preventive strategies related to dietary and environmental modulators in PD might be clinically useful in the future.

Systemic lupus erythematosus is associated with increased risk of Parkinson’s disease

Background: A small number of studies have suggested an association between systemic lupus erythematosus (SLE) and Parkinson’s disease (PD). Objectives: This study aimed to determine the risk of incident PD among Korean patients with SLE. Design: A nationwide retrospective cohort study using the claims database of the National Health Insurance Service of Korea was conducted. Methods: Patients above 40 years of age diagnosed with SLE between 2010 and 2015 were included in the study. The primary outcome of the study was incident PD, defined by registration in the rare intractable diseases program for PD and an ICD-10 code of G20. Subjects were followed until PD diagnosis or the end of 2017. We estimated the cumulative incidence of PD among the SLE cohort and compared this to that in a 1:5 age- and sex-matched control group. Results: Totals of 11,615 SLE cases and 58,075 matched controls were identified. The cumulative incidence rate of PD was 0.7 per 1000 person-years in the SLE cohort. The crude hazard ratio (HR) of incident PD was 1.71 (95% CI: 1.25–2.36) among the SLE cohort compared to the control group. The HR was 1.59 (95% CI: 1.15–2.20) after adjustment for age, sex, income, and baseline comorbidities. Conclusion: This study demonstrated that patients with SLE had an increased risk of incident PD compared to non-SLE controls. Further research is required to determine the mechanism underlying this and to elucidate the precise role of systemic inflammation in the development of PD in patients with SLE.

Incidence of Parkinson disease in North America

Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.

Reproductive characteristics, use of exogenous hormones and Parkinson disease in women from the E3N study.

Despite experimental studies suggesting a disease-modifying role of oestrogens, results from epidemiological studies on the relation of reproductive characteristics and hormonal exposures with Parkinson disease in women are conflicting. We used the data from the E3N cohort study including 98 068 women aged 40-65 years in 1990 followed until 2018. Parkinson disease was ascertained using a validation process based on drug claim databases and medical records. Reproductive characteristics and hormonal exposures were self-reported (11 questionnaires). Associations of exposures with Parkinson disease incidence were investigated using time-varying Cox proportional hazards regression with a 5-year exposure lag and age as the timescale adjusted for confounders. We identified 1165 incident Parkinson disease cases during a mean follow-up of 22.0 years (incidence rate = 54.7 per 100 000 person-years). Parkinson disease incidence was higher in women with early (<12 years, HR = 1.21, 95% CI = 1.04-1.40) or late age at menarche (≥14 years, HR = 1.18, 95% CI = 1.03-1.35) than in women with menarche at 12-13 years. Nulliparity was not associated with Parkinson disease, but Parkinson disease incidence increased with the number of children in parous women (P-trend = 0.009). Women with artificial (surgical, iatrogenic) menopause were at greater risk than women with natural menopause (HR = 1.28, 95% CI = 1.09-1.47), especially when artificial menopause occurred at an early age (≤45.0 years). Postmenopausal hormone therapy tended to mitigate greater risk associated with artificial or early menopause (≤45.0 years). While fertility treatments were not associated with Parkinson disease overall, ever users of clomiphene were at greater Parkinson disease risk than never users (HR = 1.81, 95% CI = 1.14-2.88). Other exposures (breastfeeding, oral contraceptives) were not associated with Parkinson disease. Our findings suggest that early and late age at menarche, higher parity, and artificial menopause, in particular at an early age, are associated with increased Parkinson disease incidence in women. In addition, there was some evidence that use of exogenous hormones may increase (fertility treatments) or decrease (postmenopausal hormone therapy) Parkinson disease incidence. These findings support the hypothesis that hormonal exposures play a role in the susceptibility to neurodegenerative diseases. If confirmed, they could help to identify subgroups at high risk for Parkinson disease.

Melanin and Neuromelanin: Linking Skin Pigmentation and Parkinson's Disease.

Neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the most vulnerable neurons in Parkinson's disease (PD). Recent work suggests that the accumulation of oxidized dopamine and neuromelanin mediate the convergence of mitochondrial and lysosomal dysfunction in patient-derived neurons. In addition, the expression of human tyrosinase in mouse SNpc led to the formation of neuromelanin resulting in the degeneration of nigral dopaminergic neurons, further highlighting the importance of neuromelanin in PD. The potential role of neuromelanin in PD pathogenesis has been supported by epidemiological observations, whereby individuals with lighter pigmentation or cutaneous malignant melanoma exhibit higher incidence of PD. Because neuromelanin and melanin share many functional characteristics and overlapping biosynthetic pathways, it has been postulated that genes involved in skin pigmentation and melanin formation may play a role in the susceptibility of vulnerable midbrain dopaminergic neurons to neurodegeneration. Here, we highlight potential mechanisms that may explain the link between skin pigmentation and PD, focusing on the role of skin pigmentation genes in the pathogenesis of PD. We also discuss the importance of genetic ancestry in assessing the contribution of pigmentation-related genes to risk of PD. © 2022 International Parkinson and Movement Disorder Society.