Subsequent Parkinson's Disease Research Articles

Risk of subsequent Parkinson's disease among patients with bipolar disorder or major depression: A nationwide longitudinal study in Taiwan.

Bipolar disorder (BD) and major depression have been associated with an increased risk of developing Parkinson's disease (PD); however, few studies have directly compared the risk of PD development between patients with BD and major depression while considering relevant risk factors and psychotropic medications. Using the Taiwan National Health Insurance Research Database, 21,186 patients with BD, 21,188 patients with major depression, and 42,374 controls were enrolled between 2001 and 2009, and followed until the end of 2011. Individuals who developed PD during the follow-up period were identified. Cox regression models were used to analyze the hazard ratio (HR) of developing PD, adjusting for demographic factors, comorbidities, and psychotropic medication usage. Both patients with BD [HR 8.63, 95% confidence interval (CI) 6.35-11.72] and those with major depression (HR 5.68, 95% CI 4.15-7.78) had an elevated risk of subsequent PD compared to the controls. Patients with BD were associated with a 51% increased risk of subsequent PD compared with patients with major depression. Long-term treatment with antiepileptic mood stabilizers was associated with increased PD risk among patients with late-onset BD and high Charlson comorbidity index scores. Lithium was not associated with an increased PD risk. The study highlights an elevated PD risk in patients with BD and major depression compared to the controls, with BD patients at highest risk. Further research is needed to elucidate the complex interplay between psychotropic medications and neurodegenerative processes in BD, aiming to optimize therapeutic strategies and improve patient outcomes.

α-Synuclein Conformations in Plasma Distinguish Parkinson's Disease from Dementia with Lewy Bodies.

Aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Evidence exists for aSyn "strains" - conformations with distinct biological properties. However, biomarkers for PD vs. DLB, including potential aSyn strain differences, are lacking. Here, we used two monoclonal antibodies selective for different in vitro aSyn species - termed Strain A and B - to evaluate human brain tissue, cerebrospinal fluid (CSF), and plasma. Surprisingly, levels of Strain A and B aSyn species differed in plasma from individuals with PD vs. DLB in two independent cohorts. Lower plasma aSyn Strain A species also predicted subsequent PD cognitive decline. Strain A and Strain B aSyn species were undetectable in CSF, but plasma aSyn species could template aSyn fibrillization, particularly in PD. Our findings suggest that aSyn strains may impact LBD clinical presentation and originate outside the brain.

Investigating the Connection between Chronic Periodontitis and Parkinson's Disease: Findings from a Korean National Cohort Study.

Recent research suggests a potential relevance between chronic periodontitis (CP) and Parkinson's disease (PD), raising concerns about comorbid PD among elderly CP patients. However, the epidemiologic basis for this association remains unclear. Employing a nested case-control design, this study explored the association between CP and subsequent PD occurrences in Korean adults, leveraging a validated national population-based dataset covering the period from 2002 to 2019. It included 8794 PD patients and 35,176 matched control individuals, established through propensity score matching for age, sex, residential area, and income. Baseline characteristics were compared using standardized differences, and logistic regression was employed to assess the impact of CP histories on PD likelihood while controlling for covariates. We performed a thorough examination of CP events within both 1-year and 2-year intervals preceding the index date, incorporating subgroup analyses. Our analysis revealed no statistically significant association between CP history and PD development overall. However, subgroup analysis revealed a slightly increased likelihood of PD development among CP individuals with a high disease burden (Charlson Comorbidity Index score ≥ 2). In conclusion, although our study did not find a significant overall association between CP history and PD development, the elevated likelihood of PD in subgroups with high disease burden may suggest that comorbidities influence PD probability among certain CP patients. Considering comorbid conditions in PD screening for some individuals with CP may be also important.

Lifelong Association of Disorders Related to Military Trauma with Subsequent Parkinson's Disease.

Trauma-related disorders such as traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are emerging as risk factors for Parkinson's disease (PD), but their association with development of PD and independence from comorbid disorders remains unknown. To examine TBI and PTSD related to early trauma in military veterans using a case-control study. PD was identified by International Classification of Diseases (ICD) code, recurrent PD-specific prescriptions, and availability of 5+ years of earlier records. Validation was performed by chart review by a movement disorder-trained neurologist. Control subjects were matched 4:1 by age, duration of preceding health care, race, ethnicity, birth year, and sex. TBI and PTSD were identified by ICD code and onset based on active duty. Association and interaction were measured for TBI and PTSD with PD going back 60 years. Interaction was measured for comorbid disorders. A total of 71,933 cases and 287,732 controls were identified. TBI and PTSD increased odds of subsequent PD at all preceding 5-year intervals back to year -60 (odds ratio range: 1.5 [1.4, 1.7] to 2.1 [2.0, 2.1]). TBI and PTSD showed synergism (synergy index range: 1.14 [1.09, 1.29] to 1.28 [1.09, 1.51]) and additive association (odds ratio range: 2.2 [1.6, 2.8] to 2.7 [2.5, 2.8]). Chronic pain and migraine showed greatest synergy with PTSD and TBI. Effect sizes for trauma-related disorders were comparable with established prodromal disorders. TBI and PTSD are associated with later PD and are synergistic with chronic pain and migraine. These findings provide evidence for TBI and PTSD as risk factors preceding PD by decades and could aid in prognostic calculation and earlier intervention. © 2023 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Rheumatoid Arthritis and Risk of Parkinson Disease in Korea

Although it has been postulated that chronic inflammation caused by rheumatoid arthritis (RA) contributes to the development of Parkinson disease (PD), the association between these 2 conditions has yet to be determined. To evaluate the association between RA and subsequent PD risk. This retrospective cohort study used the Korean National Health Insurance Service database to collect population-based, nationally representative data on patients with RA enrolled from 2010 to 2017 and followed up until 2019 (median follow-up, 4.3 [IQR, 2.6-6.4] years after a 1-year lag). A total of 119 788 patients who were first diagnosed with RA (83 064 with seropositive RA [SPRA], 36 724 with seronegative RA [SNRA]) were identified during the study period and included those who underwent a national health checkup within 2 years before the RA diagnosis date (64 457 patients). After applying exclusion criteria (eg, age <40 years, other rheumatic diseases, previous PD), 54 680 patients (39 010 with SPRA, 15 670 with SNRA) were included. A 1:5 age- and sex-matched control group of patients without RA was also included for a total control population of 273 400. Rheumatoid arthritis as defined using International Classification of Diseases, Tenth Revision codes M05 for SPRA and M06 (except M06.1 and M06.4) for SNRA; prescription of any disease-modifying antirheumatic drug; and enrollment in the Korean Rare and Intractable Diseases program. The main outcome was newly diagnosed PD. Data were analyzed from May 10 through August 1, 2022, using Cox proportional hazards regression analyses. From the 328 080 individuals analyzed (mean [SD] age, 58.6 [10.1] years; 74.9% female and 25.1% male), 1093 developed PD (803 controls and 290 with RA). Participants with RA had a 1.74-fold higher risk of PD vs controls (95% CI, 1.52-1.99). An increased risk of PD was found in patients with SPRA (adjusted hazard ratio [aHR], 1.95; 95% CI, 1.68-2.26) but not in patients with SNRA (aHR, 1.20; 95% CI, 0.91-1.57). Compared with the SNRA group, those with SPRA had a higher risk of PD (aHR, 1.61; 95% CI, 1.20-2.16). There was no significant interaction between covariates on risk of PD. In this study, RA was associated with an increased risk of PD, and seropositivity of RA conferred an augmented risk of PD. The findings suggest that physicians should be aware of the elevated risk of PD in patients with RA and promptly refer patients to a neurologist at onset of early motor symptoms of PD without synovitis.

Development of Parkinson Disease and Its Relationship with Incidentally Discovered White Matter Disease and Covert Brain Infarction in a Real-World Cohort.

This study aimed to examine the relationship between covert cerebrovascular disease, comprised of covert brain infarction and white matter disease, discovered incidentally in routine care, and subsequent Parkinson disease. Patients were ≥50 years and received neuroimaging for non-stroke indications in the Kaiser Permanente Southern California system from 2009 to 2019. Natural language processing identified incidentally discovered covert brain infarction and white matter disease and classified white matter disease severity. The Parkinson disease outcome was defined as 2 ICD diagnosis codes. 230,062 patients were included (median follow-up 3.72 years). A total of 1,941 Parkinson disease cases were identified (median time-to-event 2.35 years). Natural language processing identified covert cerebrovascular disease in 70,592 (30.7%) patients, 10,622 (4.6%) with covert brain infarction and 65,814 (28.6%) with white matter disease. After adjustment for known risk factors, white matter disease was associated with Parkinson disease (hazard ratio 1.67 [95%CI, 1.44, 1.93] for patients <70 years and 1.33 [1.18, 1.50] for those ≥70 years). Greater severity of white matter disease was associated with increased incidence of Parkinson disease(/1,000 person-years), from 1.52 (1.43, 1.61) in patients without white matter disease to 4.90 (3.86, 6.13) in those with severe disease. Findings were robust when more specific definitions of Parkinson disease were used. Covert brain infarction was not associated with Parkinson disease (adjusted hazard ratio=1.05 [0.88, 1.24]). Incidentally discovered white matter disease was associated with subsequent Parkinson disease, an association strengthened with younger age and increased white matter disease severity. Incidentally discovered covert brain infarction did not appear to be associated with subsequent Parkinson disease. ANN NEUROL 2022;92:620-630.

Obsessive-Compulsive Disorder and Risk of Parkinson Disease: A Nationwide Longitudinal Study.

Several small-scale studies have suggested a biological link between obsessive-compulsive disorder (OCD) and Parkinson disease (PD). However, the temporal association of OCD and subsequent PD remained unclear. Here, we used Taiwan National Health Insurance Research Database and included the data of 28,722 patients with OCD ( International Classification of Diseases, Ninth Revision, Clinical Modification code: 300.3) and 287,220 matched controls between 2001 and 2009. They were followed until the end of 2011 to identify diagnosis of new-onset PD ( International Classification of Diseases, Ninth Revision, Clinical Modification code: 332.0). The frequency of psychiatric outpatient visits for OCD per year (<5, 5-10, and >10) was identified as a proxy of OCD severity. Using the stratified Cox regression model, the hazard ratio of developing PD among patients with OCD was 2.70 (95% confidence interval = 1.74-4.18) compared with matched controls. Among patients with OCD, those with >10 psychiatric outpatient visits per year for OCD (hazard ratio = 3.18, 95% confidence interval = 2.06-4.93) were more likely to develop PD during the follow-up period compared with those with <5 psychiatric outpatient visits per years for OCD. OCD was found to be an independent risk factor for PD. The mechanisms underlying the temporal association between OCD and subsequent PD require further investigation.

Prodromal depression and subsequent risk of developing Parkinson's disease: a systematic review with meta-analysis.

Aim: Parkinson's disease (PD) is a progressive neurological disorder that predominately affects dopaminergic neurons. We believe that this pooling of data will help to better understand the prodromal nature of depression in PD. Materials & methods: We conducted this study in accordance with PRISMA guidelines 2020. Fifteen eligible articles were shortlisted for final analysis. Risk of bias assessment was also conducted Results: The random-effect model revealed that the risk of subsequent PD in patients with prodromal depression was twice as likely (odds ratio, 2.04; 95% CI, 1.02-4.08) as compared with a healthy population. Conclusion: Our meta-analysis concluded that the subsequent risk of PD is significantly higher in patients with depression as compared with healthy individuals.

Prediabetes, type 2 diabetes mellitus and risk of Parkinson’s disease: A population-based cohort study

BackgroundAssociation of type 2 diabetes mellitus (T2D) with subsequent Parkinson's disease (PD) has supported the link between glucose metabolism and PD. We assessed the risk of PD not only in T2D but also in prediabetes. MethodsWe conducted a retrospective cohort study of the population attended in primary care centres of the Catalan Health Institute in Catalonia between 2006 and 2018. The data were obtained from the Information System for Research in Primary Care (SIDIAP). We created a cohort of T2D and prediabetes patients (HbA1c ≥ 5.7–6.4% without antidiabetic drugs or previous T2D diagnosis) and compared to a reference cohort. The outcome was PD diagnosis and we excluded PD before or during the first year of follow-up. We used multivariate Cox regression models to calculate hazard ratios (HR) and 95% confidence intervals (95%CI). We excluded subjects with atypical and secondary parkinsonisms. ResultsThe exposed cohorts comprised of 281.153 patients with T2D and 266.379 with prediabetes and a reference cohort of 2.556.928 subjects. T2D and prediabetes were associated with higher risk of PD (HRadjusted 1.19, 95%CI 1.13–1.25, and 1.07, 1.00–1.14; respectively). In analyses stratified by sex, prediabetes was only associated with PD risk in women (1.12, 1.03–1.22 vs. 1.01, 0.99–1.10 in men). When analysis was stratified by age, T2D and prediabetes were associated with a greater PD risk both in women (2.36, 1.96–2.84 and 2.10, 1.70–2.59 respectively) and men (1.74, 1.52–2.00 and 1.90, 1.57–2.30 respectively) below 65 years-old. ConclusionsWe report for the first time that prediabetes increases the odds of subsequent PD and replicate the association with established T2D. Both associations predominate in women and young individuals.

Lower Lymphocyte Count is Associated With Increased Risk of Parkinson's Disease.

Objectives:Patients with established Parkinson’s disease (PD) display differences in peripheral blood markers of immune function, including leukocyte differential counts, compared with controls. These differences may be useful biomarkers to predict PD and may shed light on pathogenesis. We sought to identify whether peripheral immune dysregulation was associated with increased risk of subsequent PD diagnosis.Methods:We examined the relationship between incident PD, baseline differential leukocyte count and other blood markers of acute inflammation in UK Biobank (UKB), a longitudinal cohort with ~500,000 participants. We used a range of sensitivity analyses and Mendelian randomization (MR) to further explore the nature of associations.Results:After excluding individuals with comorbidities which could influence biomarkers of inflammation, 465 incident PD cases and 312,125 controls remained. Lower lymphocyte count was associated with increased risk of subsequent PD diagnosis (per 1-SD decrease in lymphocyte count odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.07–1.32, padjusted = 0.01). There was some evidence that reductions in eosinophil counts, monocyte counts and C-reactive protein (CRP) were associated with increased PD risk, and that higher neutrophil count was also associated. Only the association between lower lymphocyte count and increased PD risk remained robust to sensitivity analyses. MR suggested that the effect of lower lymphocyte count on PD risk may be causal (per 1-SD decrease in lymphocyte count; ORMR = 1.09, 95% CI = 1.01–1.18, p = 0.02).Interpretation:We provide converging evidence from observational analyses in UKB and MR that lower lymphocyte count is associated with an increased risk of subsequent PD.

Dietary nicotine intake and risk of Parkinson disease: a prospective study

Tobacco use was observed to be associated with a lower risk of Parkinson disease (PD) in previous epidemiologic studies, with nicotine as a potential candidate. The association between dietary nicotine and PD risk has, however, not been examined in prospective studies yet. We aimed to examine prospectively the association between dietary nicotine intake and subsequent PD risk among never-smokers. The current study was based on never-smoker participants from 2 large prospective cohorts: the Nurses' Health Study (n=31,615) and the Health Professionals Follow-up Study (n=19,523). The studies contained information on dietary nicotine intake from 1986 from validated FFQs. Dietary nicotine intake was calculated based on consumption of peppers, tomatoes, processed tomatoes, potatoes, and tea. Incident cases of PD were identified via questionnaires and subsequently confirmed by reviewing medical records. We used Cox proportional hazard models to calculate cohort-specific HRs, and used fixed-effects models to calculate the pooled HR. During 26 y of follow-up, we identified 601 incident PD cases (296 women and 305 men). After adjusting for potential covariates, the pooled HR for the highest compared with the lowest quintile of dietary nicotine intake was 0.70 (95% CI: 0.51, 0.94). The significant inverse association was, however, only observed in women (adjusted HR: 0.64; 95% CI: 0.42, 0.96), not in men (adjusted HR: 0.77; 95% CI: 0.50, 1.20). Further adjusting for environmental tobacco smoke exposure, family history of PD, and use of ibuprofen generated similar significant results in women. Consistently, greater consumption of peppers was associated with lower risk of PD (adjusted HR for ≥5 times/wk compared with ≤3 times/mo: 0.49; 95% CI: 0.25, 0.94) in women but not in men (adjusted HR: 1.04; 95% CI: 0.57, 1.90). Women with greater dietary nicotine intake had a lower risk of PD than those with lower intake.

Long-Term Outcomes in Patients with Slow-Transit Constipation

Slow-transit constipation (STC) is a common disorder, and an association between STC and subsequent Parkinson disease (PD) development exists. However,

Risk of Parkinson\u2019s disease following gout: a population-based retrospective cohort study in Taiwan

BackgroundThe progressive neurodegenerative disorder Parkinson disease (PD) is well-established as the second most common neurodegenerative disease. Associations between the sequential risk of PD and gout have been addressed in other studies, but findings have been inconclusive. Accordingly, we executed the present study with the purpose of assessing PD risk in patients with gout.MethodsFrom Taiwan’s National Health Insurance Research Database, we identified the data of patients newly diagnosed as having gout between January 1, 2000 and December 1, 2000. A cohort of patients without gout, matched for sex and age, was constructed for comparison. Hazard ratios (HRs) and the incidence rate of subsequent PD were calculated for both cohorts and separately for male and female groups. The gout and comparison cohorts consisted of 7900 patients each.ResultsThe HR for PD was not significantly higher in the gout cohort compared with the control cohort (HR 1.01, 95% confidence interval [CI], 0.93–1.31, P = .268), even after adjustment for age, urbanization, monthly income, sex, and comorbidities. We did not observe gender differences in the gout–PD association (male: HR 1.01, 95% CI, 0.88–1.36, P = .400; female: HR 1.11, 95% CI, 0.84–1.46, P = .466).ConclusionsOur study identified that there was no protective effect of gout for the risk of PD in the Taiwanese population.

Clostridium difficile infection and risk of Parkinson's disease: a Swedish population-based cohort study.

Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). The aim of this study was to examine whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD. We performed a population-based cohort study using Swedish national register data. Adults aged ≥35years were identified from the Swedish Population and Housing Census 1990 and followed during the period 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs. outpatient), presence of recurrent infections, and pre-infection use of antibiotics. Amongst the study population (N=4670423), 34868 (0.75%) had a history of CDI. A total of 165 and 47035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among the CDI group [hazard ratio 1.16, 95% confidence interval (CI)1.00-1.36], which was mainly driven by increased PD risk within the first 2years after CDI diagnosis (hazard ratio 1.38, 95% CI 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups. Clostridium difficile may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.

Use of antidepressants and the risk of Parkinson's disease in the Local Health Trust of Bologna: A historical cohort study

BackgroundDepression is considered one of the prodromal symptoms of Parkinson's disease (PD) along with sleep disorders, hyposmia and constipation. Prodromal symptoms refer to the stage wherein early motor symptoms and signs allowing a diagnosis of PD are not yet present. The objective of this study was to investigate the association between the use of antidepressants, as indirect measure of depression, and subsequent PD onset, clinically diagnosed, in the Local Health Trust of Bologna, Italy. MethodsHistorical cohort study with use of antidepressants as exposure and PD onset as outcome. The cohort considered consisted of inhabitants of Bologna aged ≥35 years in 2005; those who had used antidepressants in the previous 3 years were excluded. Subjects were followed up from 2006 and until PD onset, migration out of Bologna, death or end of the study period (2017), whichever came first. “The ParkLink Bologna” system was used to detect disease onset. “ParkLink Bologna” is a research study including patients with a clinical diagnosis of PD residing in Bologna. Residents that used antidepressants for at least 180 consecutive days within 1 year were considered exposed. Hazard ratios (HR) and 95% confidence interval (CI) were estimated with Cox proportional hazards models, using exposure as time-dependent variable and adjusting for potential confounders: age, gender, use of medical care and comorbidities. ResultsFrom 2006 to 2017 199,093 person-years were exposed and 4,286,470 not exposed. Fifty-one subjects with PD were identified in the exposed group and 556 subjects in the non-exposed showing an association of adjusted HR = 1.7 (CI 1.3–2.3). The association was stronger for males (HR 2.2, CI 1.5–3.2) compared to females (HR 1.2, CI 0.8–1.9), for subjects ≤65 years of age (HR 2.4, CI 1.6–3.6) vs. >65 years (HR 1.3, CI 0.8–1.9) and for those with less comorbidities. Age and gender were confounders in the associations between antidepressant use and PD onset. ConclusionsThe use of antidepressants as indirect measure of depression is associated with the subsequent development of PD. Our findings confirm that depression may precede the onset of motor symptoms in PD. The association is stronger for younger subjects, who are males and with fewer comorbidities.

Editors' note: Association between diabetes and subsequent Parkinson disease: A record-linkage cohort study

In the article “Association between diabetes and subsequent Parkinson disease: A record-linkage cohort study,” De Pablo-Fernández et al. reported an increased rate of subsequent Parkinson disease (PD) following a diagnosis of type 2 diabetes mellitus (T2DM) in a large cohort. In response, Dr. Wei-Lai highlights conflicting results from other studies that found a negative or no association between diabetes and PD, and suggests that surveillance bias from greater medical care in patients with T2DM may result in higher rates of PD diagnoses. In their reply, authors De Pablo-Fernández et al. counter that a meta-analysis of prospective cohort studies showed an increased risk of subsequent PD in patients with T2DM, whereas conflicting results were generally case–control studies that are more prone to bias. They also highlight key strengths of their study including large sample size, derivation from National Health Service data, and measures to mitigate surveillance bias that included controlling for total hospital admissions and excluding those diagnosed with PD within a year of T2DM diagnosis. In the article “Women physicians underrepresented in American Academy of Neurology recognition awards,” Silver et al. reported that women were often underrepresented, particularly for highly prestigious awards, in lists of individual recipients over the 63-year history of the American Academy of Neurology recognition awards. In response, Dr. Ortega attributes this disparity to women struggling with competing demands of workplace productivity and motherhood.

Author response: Association between diabetes and subsequent Parkinson disease: A record-linkage cohort study.

We appreciate the interest of Dr. Lai in our recent study.1 Despite previous conflicting results, a meta-analysis of prospective cohort studies showed an increased risk of subsequent Parkinson disease (PD) in patients with type 2 diabetes mellitus (T2DM).2 Cohort studies provide more robust evidence to establish causation, whereas case–control studies can only demonstrate association between variables without information on the direction of the relationship and are more prone to bias. Our study is the largest by far on this topic, with 2,017,115 patients with T2DM, compared to 681,000 in cohort studies,2 and the pooled population of 105,974 of case–control studies.3 We mitigated against any potential surveillance bias by controlling the results by total number of hospital admissions and excluding individuals diagnosed with PD within a year of the diagnosis of T2DM without materially affecting the results. Therefore, the possibility of surveillance bias limiting our results is negligible. Our data were obtained from National Health Service hospital admissions in England and, given that health care is free to access, they are considered to be representative of the population and the closest approximation to real-world data that any study in this area has obtained.

Reader response: Association between diabetes and subsequent Parkinson disease: A record-linkage cohort study

The article by De Pablo-Fernandez et al.1 reported that type 2 diabetes mellitus (DM) was associated with increased hazard of Parkinson disease (PD) (hazard ratio 1.32, 95% confidence interval 1.29–1.35). The authors proposed that DM and PD might share a similar genetic predisposition with potential opportunities to develop therapeutic strategies.1 To the contrary, other studies revealed a negative association or no association between DM and PD.2,3 One meta-analysis revealed data from cohort studies that suggested DM being associated with an increased risk of PD, but case–control studies did not reveal such an association.4 There seems to be no conclusive evidence on this association.

Association between diabetes and subsequent Parkinson disease: A record-linkage cohort study.

To investigate the association between type 2 diabetes mellitus (T2DM) and subsequent Parkinson disease (PD). Linked English national Hospital Episode Statistics and mortality data (1999-2011) were used to conduct a retrospective cohort study. A cohort of individuals admitted for hospital care with a coded diagnosis of T2DM was constructed, and compared to a reference cohort. Subsequent PD risk was estimated using Cox regression models. Individuals with a coded diagnosis of cerebrovascular disease, vascular parkinsonism, drug-induced parkinsonism, and normal pressure hydrocephalus were excluded from the analysis. A total of 2,017,115 individuals entered the T2DM cohort and 6,173,208 entered the reference cohort. There were significantly elevated rates of PD following T2DM (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.29-1.35; p < 0.001). The relative increase was greater in those with complicated T2DM (HR 1.49, 95% CI 1.42-1.56) and when comparing younger individuals (HR 3.81, 95% CI 2.84-5.11 in age group 25-44 years). We report an increased rate of subsequent PD following T2DM in this large cohort study. These findings may reflect shared genetic predisposition and/or disrupted shared pathogenic pathways with potential clinical and therapeutic implications.

Dementia and vagotomy in Taiwan: a population-based cohort study

ObjectiveTruncal vagotomy is associated with a decreased risk of subsequent Parkinson disease (PD), although the effect of vagotomy on dementia is unclear. In response, we investigated the risk of dementia...