Parkinson's Disease In People Research Articles

SGLT2 Inhibitor Use and Risk of Dementia and Parkinson Disease Among Patients With Type 2 Diabetes.

Despite the mechanistic potential of sodium-glucose cotransporter 2 inhibitor (SGLT2i) to improve neurologic outcomes, the efficacy of SGLT2i in neurodegenerative disorders among patients with type 2 diabetes is not well established. This population-based cohort study aimed to investigate the association of SGLT2i use with risks of incident dementia and Parkinson disease (PD) in patients with type 2 diabetes. This was a retrospective examination of data from a cohort of 1,348,362 participants with type 2 diabetes (≥40 years), who started antidiabetic drugs from 2014 to 2019, evaluated using the Korean National Health Insurance Service Database. Propensity score matching (1:1; SGLT2i to other oral antidiabetic drugs [OADs]) produced a cohort of 358,862 participants. Primary outcomes were the individual incidence of Alzheimer disease (AD), vascular dementia (VaD), and PD. Secondary outcomes were all-cause dementia (AD, VaD, and other dementia) and a composite of all-cause dementia and PD. Cox proportional hazards models were used to investigate the association between SGLT2i use and the risks of dementia and PD. From the 358,862 participants analyzed (mean [SD] age, 57.8 [9.6] years; 58.0% male), 6,837 incident dementia or PD events occurred. Regarding the individual endpoints, SGLT2i use was associated with reduced risks of AD (adjusted hazard ratio [aHR] 0.81, 95% CI 0.76-0.87), VaD (aHR 0.69, 95% CI 0.60-0.78), and PD (aHR 0.80, 95% CI 0.69-0.91) with a 6-month drug use lag period. In addition, use of SGLT2i was associated with a 21% lower risk of all-cause dementia (aHR 0.79, 95% CI 0.69-0.90) and a 22% lower risk of all-cause dementia and PD than use of other OADs (aHR 0.78, 95% CI 0.73-0.83). The association between the use of SGLT2i and the lowered risk of these neurodegenerative disorders was not affected by sex, Charlson Comorbidity Index, diabetic complications, comorbidities, and medications. Sensitivity analysis further adjusting for bioclinical variables from health screening tests, including blood pressure, glucose, lipid profiles, and kidney function, yielded generally consistent results. In this nationwide population-based study, SGLT2i use significantly reduced the risks of neurodegenerative disorders in patients with type 2 diabetes independent of various factors including comorbidities and bioclinical parameters. This study provides Class II evidence that SGLT2 antidiabetic drugs decrease the risk of dementia and PD in people with diabetes.

Association between the Val66Met (rs6265) polymorphism of the brain-derived neurotrophic factor (BDNF) gene, BDNF protein level in the blood and the risk of developing early‑onset Parkinson's disease.

Brain-derived neurotrophic factor (BDNF) is involved in the maintenance of dopamine level and the survival of dopaminergic neurons, which may affect the functionality of brain structures responsible for motor and cognitive function. The aim of the study was to assess the association of individual and combined single nucleotide polymorphism (SNP) in the rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) genes with early‑onset of Parkinson's disease (PD) patients. Moreover, we assessed the association between the BDNF Val66Met polymorphism and the level of BDNF protein in the serum of patients with PD and controls. The study involved 163 patients with idiopathic PD divided into early onset (<55 years) and late‑onset (>55 years) groups and 91 healthy age‑matched people (Control). The SNP were determined using the TaqMan Real‑Time PCR method. Serum BDNF levels were determined by ELISA assay. The risk of developing early PD in people with the BDNF genotype AG increases threefold in comparison with the carriers of the BDNF genotype GG. In PD patients and healthy people with the BDNF genotypes AG and AA, a lower serum BDNF level was found compared to those with the BDNF genotype GG in both groups. The results of our study indicate that the presence of the Val66Met BDNF gene polymorphism is associated with reduced blood BDNF levels and an elevated risk of developing early‑onset PD. This effect appears to be more pronounced in men.

Occupational Pesticide Exposure in Parkinson's Disease Related to GBA and LRRK2 Variants.

The penetrance of common genetic risk variants for Parkinson's disease (PD) is low. Pesticide exposure increases PD risk, but how exposure affects penetrance is not well understood. To determine the relationship between occupational pesticide exposure and PD in people with LRRK2 and GBA risk variants. Participants of the Parkinson's Progression Markers Initiative (PPMI) with a LRRK2-G2019 S or GBA risk variant provided information about occupational pesticide exposure. We compared exposure in carriers with and without PD. Among carriers with PD, we used Cox proportional hazard models to compare time-to impairment in balance, cognition, and activities of daily living (ADLs) between participants with and without prior occupational pesticide exposure. 378 participants with a risk variant provided exposure information; 176 with LRRK2-G2019 S (54 with and 122 without PD) and 202 with GBA variants (47 with and 155 without PD). Twenty-six participants reported pesticide exposure. People with a GBA variant and occupational pesticide exposure had much higher odds of PD (aOR: 5.4, 95% CI 1.7-18.5, p < 0.01). People with a LRRK2 variant and a history of occupational pesticide exposure had non-significantly elevated odds of PD (aOR 1.3, 95% CI 0.4-4.6, p = 0.7). Among those with PD, pesticide exposure was associated with a higher risk of balance problems and cognitive impairment in LRRK2-PD and functional impairment in GBA-PD, although associations were not statistically significant. Occupational pesticide exposure may increase penetrance of GBA-PD and may be associated with faster symptom progression. Further studies in larger cohorts are necessary.

Risk of Parkinson's disease in people aged ≥50 years with new-onset anxiety: a retrospective cohort study in UK primary care.

A history of anxiety is more common in people with Parkinson's disease (PD). The prospective risk of PD in those newly presenting with anxiety and factors that increase the risk of PD in patients with anxiety have not been investigated. To investigate the incidence of PD in people with anxiety aged ≥50 years and clinical features associated with later diagnosis of PD in people with anxiety. A retrospective cohort study using UK primary care data between 2008 and 2018, assessing patients with new-onset anxiety aged ≥50 years. Weibull survival regression models were fitted and hazard ratios (HRs) for modelling time-to-PD was estimated in those with and without anxiety, and when determining the risk of developing PD in those with anxiety. Results were adjusted for sociodemographic and lifestyle factors, and relevant physical and mental health conditions. The risk of PD increased two-fold compared with the non-anxiety group after adjustment for age, sex, social deprivation, lifestyle factors, severe mental illness, head trauma, and dementia (HR 2.1, 95% confidence interval = 1.9 to 2.4). In those with anxiety, the presence of depression, hypotension, tremor, rigidity, balance impairment, constipation, sleep disturbance, fatigue, and cognitive impairment were associated with an increased risk of developing PD. The risk of developing PD was at least doubled in people with anxiety compared with those without. The clinical features of those who developed PD can help identify patients presenting with anxiety who are in the prodromal phase of PD.

To know or not to know? Opinions of patients with Parkinson's Disease on disclosing risk of phenoconversion in RBD.

The aim of our study was to find out the opinion of patients with Parkinson's Disease (PD) whose disease was preceded by REM sleep behaviour disorder (RBD) regarding early information about the high risk of phenoconversion in RBD. RBD is an early clinical manifestation of α-synucleinopathies with a more than 90% risk of phenoconversion to PD, dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). It remains a subject for debate as to whether and how RBD patients should be informed about the high risk of phenoconversion. The patient's right to full knowledge regarding his or her health conflicts with the potentially destructive impact of this information on his or her mental state and quality of life of them and their relatives. Thirty-nine patients with PD whose disease was preceded by RBD were surveyed. Data on the course of RBD and PD was collected. Questions were asked about early information about the high risk of phenoconversion to patients with RBD and factors determining the opinion of the surveyed persons. The majority ( > 60%) of respondents gave a positive answer when asked whether patients should be informed about their high risk of developing PD once diagnosed with RBD. Only a few (7.7%) respondents believed that disclosing such information to the patient should be possible only after obtaining his or her consent. Respondents associated consent to information about the high risk of developing PD in people with RBD with high expectations of the healthcare system. We were unable to determine whether factors such as the gender of the subject, the clinical course of the PD, and the RBD duration had an impact on patients' opinions regarding disclosing knowledge about phenoconversion. Our study provides important information that should influence physicians' communication with patients with RBD, especially regarding how they communicate about the high risk of phenoconversion.

Exercise knowledge, barriers and motivators among LRRK2 G2019S mutation carriers

IntroductionPeople with a Gly2019Ser mutation in the leucine-rich repeat kinase 2 (LRRK2 G2019S) are at increased risk of developing Parkinson's disease (PD). Recent evidence suggests that exercise may delay or prevent the development of clinically overt symptoms of PD in people at risk of PD. We determined whether LRRK2 G2019S mutation carriers with and without manifest PD are aware of the relationship between exercise and PD and how they differ in awareness, barriers and motivators to exercise. MethodsWe deployed a survey among 4422 LRRK2 G2019S mutation carriers. In total, 505 (11.4%) of them completed the survey, of whom 105 had self-reported manifest PD. ResultsNinety-two percent of the LRRK2 G2019S mutation carriers with manifest PD and 63% of those with non-manifest PD were aware of the relationship between exercise and PD. Lack of motivation was the top barrier for those without manifest PD, while having an injury/disability was the most common barrier for those with manifest PD. Improvement of body functioning was the top motivator for both. ConclusionThe fact that many at-risk individuals are not aware of the importance of exercise and would exercise more with fewer barriers creates opportunities for trials using exercise as a possible prevention strategy for PD.

Disease-Modifying Antirheumatic Drugs and Risk of Parkinson Disease: Nested Case-Control Study of People With Rheumatoid Arthritis.

Background and ObjectivesEpidemiologic studies have suggested a link between rheumatoid arthritis and Parkinson disease (PD). Disease-modifying antirheumatic drugs (DMARDs) might explain this association. The aim of this work was to evaluate the association between DMARDs and risk of PD in persons with rheumatoid arthritis.MethodsThis nested nationwide case-control study was conducted within the Finnish Parkinson's Disease (FINPARK) cohort, which includes 22,189 Finnish persons with clinically verified PD diagnosed in 1996 to 2015. The cases had recorded diagnosis of PD in the Special Reimbursement Register and had no exclusion diagnoses with symptoms that may be confused with PD within 2 years of PD diagnosis. This study included cases with PD diagnosed during 1999 to 2015 and rheumatoid arthritis diagnosed >3 years before PD. Rheumatoid arthritis was identified from the Finnish Care Register for Health Care and Special Reimbursement Register. Cases were matched with up to 7 controls by age, sex, duration of rheumatoid arthritis, and region. DMARDs were categorized into 5 classes, and data on purchased prescriptions were identified from the Prescription Register since 1995. Associations were studied with conditional logistic regression adjusted for confounders.ResultsAltogether, 315 cases with PD and 1,571 matched controls were included. The majority (>60%) were women, and the median duration of rheumatoid arthritis on matching date was 11.6 years for controls and 12.6 years for cases. Use of DMARDs was not associated with risk of PD with a 3-year lag period applied between exposure and outcome except chloroquine/hydroxychloroquine, which associated with decreased risk (adjusted odds ratio [OR] 0.74, 95% confidence interval [CI] 0.56–0.97). Other DMARDs, including sulfasalazine, methotrexate, gold preparations, and immunosuppressants, were not associated with PD.DiscussionOur results suggest that the lower risk of PD in people with rheumatoid arthritis is not explained by DMARD use because these drugs in general did not modify the risk of PD among persons with rheumatoid arthritis. Association between chloroquine/hydroxychloroquine and lower risk of PD and the possible underlying mechanisms should be further investigated.Classification of EvidenceThis study provides Class II evidence that in individuals with rheumatoid arthritis using DMARDs, only chloroquine/hydroxychloroquine was associated with a potentially decreased risk of developing PD (adjusted OR 0.74, 95% CI 0.56–0.97).

Thiazolidinedione use is associated with reduced risk of Parkinson's disease in patients with diabetes: a meta-analysis of real-world evidence.

The thiazolidinedione (TZD) class of oral antidiabetic agents are used to treat type 2 diabetes mellitus (DM). This meta-analysis aimed to understand the protective effect of TZD on Parkinson's disease (PD) in people with diabetes. A literature search was performed in PubMed, Embase, and Cochrane central from inception to until 30 September 2019. We included all real-world evidence studies assessing the use of TZD class of drugs and the risk of PD in people with diabetes. Quality of the studies was evaluated using the Newcastle-Ottawa scale. The primary outcome was the pooled hazard ratio (HR) of PD among type 2 DM TZD users as compared with TZD non-users in people with diabetes. The secondary outcome was the HR of PD among type 2 DM TZD users as compared with non-users (include both diabetic and nondiabetic population). Meta-analysis was performed using RevMan software. Out of five studies selected for inclusion, four studies fulfilled the criteria for primary outcomes. The participants' mean age and follow-up duration were 66.23 ± 9.59years and 5.25years (2.97-7.9years), respectively. There was a significant reduction in the risk of PD (pooled adjusted HR of 0.81 [95% CI 0.70-0.93, p = 0.004]) in TZD users compared with non-TZD users in people with diabetes. A significant protective effect of TZD was observed in Caucasian population (3 studies) (HR 0.78 (95% CI 0.66-0.92), p = 0.003). This meta-analysis demonstrates a potential neuroprotective effect of TZD for PD risk in the population with DM.

Risk of Developing Parkinson Disease in Bipolar Disorder

Parkinson disease (PD) manifests by motor and nonmotor symptoms, which may be preceded by mood disorders by more than a decade. Bipolar disorder (BD) is characterized by cyclic episodes of depression and mania. It is also suggested that dopamine might be relevant in the pathophysiology of BD. To assess the association of BD with a later diagnosis of idiopathic PD. An electronic literature search was performed of Cochrane Controlled Register of Trials, MEDLINE, Embase, and PsycINFO from database inception to May 2019 using the terms Parkinson disease, bipolar disorder, and mania, with no constraints applied. Studies that reported data on the likelihood of developing PD in BD vs non-BD populations were included. Two review authors independently conducted the study selection. Two review authors independently extracted study data. Data were pooled using a random-effects model, results were abstracted as odds ratios and 95% CIs, and heterogeneity was reported as I2. Odds ratios of PD. Seven studies were eligible for inclusion and included 4 374 211 participants overall. A previous diagnosis of BD increased the likelihood of a subsequent diagnosis of idiopathic PD (odds ratio, 3.35; 95% CI, 2.00-5.60; I2 = 92%). A sensitivity analysis was performed by removing the studies that had a high risk of bias and also showed an increased risk of PD in people with BD (odds ratio, 3.21; 95% CI, 1.89-5.45; I2 = 94%). Preplanned subgroup analyses according to study design and diagnostic certainty failed to show a significant effect. This review suggests that patients with BD have a significantly increased risk of developing PD compared with the general population. Subgroup analyses suggested a possible overestimation in the magnitude of the associations. These findings highlight the probability that BD may be associated with a later development of PD and the importance of the differential diagnosis of parkinsonism features in people with BD.

22q11.2 Deletion Syndrome-Associated Parkinson's Disease.

Background22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition associated with an increased risk of early‐onset Parkinson's disease (PD).MethodsWe review the clinical, neuroimaging, and neuropathological observations, as well as diagnostic challenges, of PD in 22q11.2DS. We conducted a search of PubMed up until June 1, 2018 and personal files to identify relevant publications.Results22q11.2DS‐associated PD is responsible for approximately 0.5% of early‐onset PD. The hallmark motor symptoms and neuropathology of PD, and typical findings of reduced striatal dopamine transporter binding with molecular imaging, are present in 22q11.2DS‐associated PD. Mean age at PD onset in 22q11.2DS is relatively young (∼40 years). Patients with 22q11.2DS‐associated PD show a good response to levodopa.ConclusionsFurther recognition of 22q11.2DS and study of PD in people with 22q11.2DS could provide insights into the mechanisms that cause PD in the general population. 22q11.2DS may serve as an identifiable PD model to study prodromal PD and disease‐modifying treatments.

Essential tremor and Parkinson's disease: Lack of a link

Essential tremor (ET) is a very common disorder and proving that there is a relationship to another common movement disorder, Parkinson's disease (PD), has been debated for years. Review of the literature for links between ET and PD primarily focused on neuropathology as well as neurochemistry, epidemiology, genetics, olfactory function, and neuroimaging. While there may be some evidence to suggest an increase in occurrence of PD in people who were previously diagnosed with ET, neuropathologic studies of ET with similarly assessed control subjects do not find an increase in Lewy bodies in the ET group. Studies of incidental Lewy body disease do not find an increase in ET or action tremor compared to controls. ET subjects as a group do not have neurochemical changes that are found in PD, do not respond to medications used to treat PD, are not hyposmic as is found in PD, and neuroimaging studies do not find changes of PD when groups are compared. The overwhelming amount of evidence suggests that any link between ET and PD is coincidental and not biological. Prospective, longitudinal cohort studies with standardized clinical and biomarker assessments followed by neuropathologic confirmation are needed.