Pre-existing Parkinson's Disease Research Articles

Hearing Loss, Incident Parkinson Disease, and Treatment With Hearing Aids

The risk of developing Parkinson disease (PD) after objective hearing loss is unknown. PD studies using self-reported hearing loss are insensitive, and objective data are lacking. To examine the association of hearing loss with incident PD in US veterans and its effect modification by well-established prodromal conditions and hearing aids. This cohort study analyzed electronic health record data from the US Department of Veterans Affairs for veterans who had an audiogram from January 1, 1999, to December 30, 2022. Individuals with data missing or a preexisting PD diagnosis were excluded. Audiogram-confirmed hearing loss. Cumulative incidence of PD was calculated with adjustment for competing risk of death. Among 7 296 051 veterans with an audiogram, 3 596 365 were included. They were mostly male (n = 3 452 898 [96%]) and had a mean (SD) age of 67 (10.3) years. A total of 750 010 individuals (20.8%) had normal hearing at the time of audiometry examination; among those with hearing loss, 1 080 651 (30.0%), 1 039 785 (28.9%), 568 296 (15.8%), and 157 623 (4.3%) individuals had mild (20-<35 dB), moderate (35-<50 dB), moderate to severe (50-<65 dB), and severe to profound (65-120 dB) hearing loss, respectively. Age, gender, and smoking history were balanced between all exposed and unexposed groups with further adjustment for race, ethnicity, and frailty. At 10 years after the baseline audiogram, the numbers of additional cases of PD were 6.1 (95% CI, 4.5-7.79, 15.8 (95% CI, 12.8-18.8), 16.2 (95% CI, 11.9-20.6), and 12.1 (95% CI, 4.5-19.6) among veterans with mild, moderate, moderate to severe, and severe to profound hearing loss, respectively, compared with those with normal hearing. When combined with established prodromal conditions, hearing loss was associated with 5.7 (95% CI, 2.2-9.2) additional cases of PD at 10 years compared with either condition alone. With prompt hearing aid dispensation, incident cases of PD decreased by 21.6 cases (95% CI, 19.5-23.6) at 10 years. Hearing loss appears to be an independent risk factor for later development of PD. Hearing aids attenuate this risk, and therefore widespread screening for hearing loss and appropriate use of hearing aids may reduce the incidence of PD. Additional studies are needed to examine the mechanisms underlying the association between hearing loss and PD.

Sodium-glucose cotransporter 2 inhibitors and the risk of Parkinson disease in real-world patients with type 2 diabetes.

Diabetes increases the risk of Parkinson disease (PD). Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new glucose-lowering therapeutic class, have shown neuroprotective effects in mechanistic studies. However, the association between SGLT2 inhibitors and PD risk in real-world populations with type 2 diabetes (T2D) remains unclear. The aim was to assess the association between SGLT2 inhibitors and the risk of PD in older populations with T2D. This retrospective cohort analysis used Medicare claims data from 2016 to 2020 to identify fee-for-service beneficiaries ≥65 years diagnosed with T2D and without pre-existing PD. The initiation of an SGLT2 inhibitor was compared with that of a dipeptidyl peptidase-4 (DPP4) inhibitor. The outcome was the first incident PD ever since the date initiating either an SGLT2 inhibitor or a DPP4 inhibitor. We employed a 1:1 propensity score matching to balance the baseline covariates between treatment groups, including sociodemographics, comorbidities and co-medications. We applied Cox regression models to assess the effect of SGLT2 inhibitors versus DPP4 inhibitors on incident PD. Of 89 330 eligible Medicare beneficiaries (mean age: 75 ± 7 years, 52% women), 0.6% (n = 537) had incident PD over the follow-up. After 1:1 propensity matching, the PD incidence was 2.5 and 3.5 events per 1000 person-years in the SGLT2 inhibitor group and DPP4 inhibitor group, respectively. The SGLT2 inhibitor group was associated with a significantly lower risk of incident PD than the DPP4 inhibitor group (hazard ratio: 0.70 [95% confidence interval: 0.55-0.89]). There is a potential trend that the risk reduction in incident PD was profound in non-Hispanic Black individuals and insulin users. Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with a significantly lower risk of incident PD in older populations with T2D.

Association Between Microscopic Colitis and Parkinson's Disease in a Swedish Population.

Gastrointestinal inflammation has been linked with Parkinson's disease (PD). Microscopic colitis (MC) is an intestinal inflammatory disease with unknown relationship with PD. This study aimed to examine the association of MC with PD risk. In this nationwide matched cohort study in Sweden, PD incidence was compared between 12,609 patients with histologically confirmed MC and a matched population cohort of 58,879 MC-free individuals and a sibling cohort comprising all unaffected siblings of the MC patients (NMC /NSibling =6281/12,351). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. During a mean follow-up of ~7 years, we identified 449 incident PD diagnoses among the MC patients and the population cohort. Overall, MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up. In the time-varying effects model, PD hazard was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals but was not different beyond 5 years after biopsy (HR: 1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted when comparing MC patients to their siblings. In a post hoc case-control analysis, we also detected a strong association between MC and preexisting PD (odds ratio: 3.46; 95% CI: 2.91, 4.12). Our findings suggest that MC may not be a risk factor for PD; instead, it may co-occur with PD as a comorbidity or develop after a diagnosis of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Coronavirus disease 2019 and neurodegenerative disease: what will the future bring?

Purpose of reviewOver 70 million people worldwide, including those with neurodegenerative disease (NDD), have been diagnosed with coronavirus disease 2019 (COVID-19) to date. We review outcomes in patients with NDD and COVID-19 and discuss the hypothesis that due to putative commonalities of neuropathogenesis, COVID-19 may unmask or trigger NDD in vulnerable individuals.Recent findingsBased on a systematic review of published literature, patients with NDD, including dementia, Parkinson's disease, and multiple sclerosis (MS) make up a significant portion of hospitalized COVID-19 patients. Such patients are likely to present with altered mental status or worsening of their preexisting neurological symptoms. Patients with NDD and poor outcomes often have high-risk comorbid conditions, including advanced age, hypertension, diabetes, obesity, and heart/lung disease. Patients with dementia including Alzheimer's disease are at higher risk for hospitalization and death, whereas those with preexisting Parkinson's disease are not. MS patients have good outcomes and disease modifying therapies do not increase the risk for severe disease. Viral infections and attendant neuroinflammation have been associated with the pathogenesis of Alzheimer's disease, Parkinson's disease, and MS, suggesting that COVID-19 may have the potential to incite or accelerate neurodegeneration.SummarySince patients with Alzheimer's disease are at higher risk for hospitalization and death in the setting of COVID-19, additional precautions and protective measures should be put in place to prevent infections and optimize management of comorbidities in this vulnerable population. Further studies are needed to determine whether COVID-19 may lead to an increased risk of developing NDD in susceptible individuals.

Impact of Comorbidities and Frailty on Early Shunt Failure in Geriatric Patients With Normal Pressure Hydrocephalus.

Background/Aim: Older patients are considered to bear a higher perioperative risk. Since idiopathic normal pressure hydrocephalus (NPH) predominantly concerns older patients, identifying risk factors for early shunt failure for preoperative risk/benefit assessment is indispensable for indication and/or consultation of patients for ventriculoperitoneal shunting (VPS).Methods: We performed a retrospective study design, including data acquired from two university hospital neurosurgical institutions between 2012 and 2019. Overall, 211 consecutive patients with clinical/radiological signs for NPH who additionally showed alleviation of symptoms after lumbar cerebrospinal fluid (CSF) drainage, received VPS and were included for further analysis. Frailty was measured using the Clinical Frailty Scale (CFS). Main outcome was early shunt failure or post-operative complications within 30 days after initial VPS surgery.Results: The overall complication rate was 14%. Patient-related complications were observed in 13 patients (6%) and procedure-related complications in 16 patients (8%). Early post-operative complications resulted in a significantly prolonged length of hospital stay 6.9 ± 6.8 vs. 10.8 ± 11.8 days (p = 0.03). Diabetes mellitus with end-organ damage (OR 35.4, 95% CI 6.6 – 189.4, p < 0.0001) as well as preexisting Parkinson's disease were associated with early patient-related post-surgical complications after VPS for NPH.Conclusions: Patients comorbidities but not frailty were associated with early post-operative patient-related complications in patients suffering NPH. While frailty may deter patients from other (neurosurgical) procedures, VPS surgery might contribute to treating NPH in these patients at a tolerable risk.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P118. Outcomes of patients with Parkinson's disease undergoing cervical spine surgery for radiculopathy and myelopathy with minimum two-year follow-up

BACKGROUND CONTEXT Parkinson's disease (PD) is a neuromuscular disorder that affects both mobility and resting tone. This may make patients susceptible to spine malalignment and frequent candidates for surgical interventions. However, there is little evidence comparing the outcomes of PD patients in cervical spinal fusion (CF). PURPOSE This study evaluated the: (1) demographics; (2) complications (medical and surgical); (3) length of stay; (4) hospital charges; (5) reoperations; and (6) readmissions following cervical spine surgery. We hypothesized that patients who have Parkinson's Disease will experience similar postoperative outcomes to other CF patients. STUDY DESIGN/SETTING Retrospective review. PATIENT SAMPLE All patients with cervical radiculopathy and myelopathy who underwent any cervical spinal fusion (anterior or posterior) between 2009 and 2011 and were eligible for at least 2-year follow-up were identified from the New York Statewide Planning and Research Cooperative System (SPARCS). Patients with Parkinson's disease were identified and propensity score matched by age, sex, and DEYO index. A total of 134 propensity score matched patients with and without PD were included. OUTCOME MEASURES Demographic information, complications, length of stay, reoperations, and readmissions. METHODS The New York Statewide Planning and Research Cooperative System (SPARCS) database was used to identify all patients with cervical radiculopathy and myelopathy who underwent any cervical spinal fusion (anterior and posterior) from 2009 to 2011 with 2-year follow-up surveillance. Patients with PD were then identified and propensity matched at a 1:1 ratio with patients without PD based on demographics and DEYO index. Demographics, insurance status, and hospital-related parameters were compared between the two groups. Logistic regression was performed to identify any predictive factors for postoperative outcomes. RESULTS There were a total of 134 CF patients included, with 67 patients in the PD group and 67 patients in the nonPD group. PD patients were less commonly white (74.6vs. 91.0%, p=.024) but all other demographics were comparable between the groups. PD patients had significantly longer length of stay (7.3vs. 3.6days, p=.004) and higher total hospital charges ($77,439.13vs. $45,761.24, p=.008) compared to nonPD patients. Overall (41.8vs. 40.3%, p=.861), medical (38.8vs. 31.3%, p=.365) and surgical (11.9vs. 11.9%, p=1) complication rates were comparable between PD and nonPD patients, respectively. However, PD patients did have higher rates of altered mental status (6.0vs. 0%, p=.042) than nonPD patients. PD patients also had comparable reoperation (14.9vs. 13.4, p=.804) and readmission (85.1vs. 74.6%, p=.132) rates as nonPD patients. Regression analysis revealed that Deyo index was the lone significant predictor of higher two-year complication (OR1.936, p .05). CONCLUSIONS This study compared 2-year outcomes between Parkinsonrs Disease and nonPD patients following cervical spinal fusion. PD patients and nonPD patients had comparable rates of complications, reoperations and readmissions at least two years after CF. PD was also not a significant predictor for any adverse outcomes. This study suggested that spine surgeons should not preclude PD patients from undergoing cervical spinal fusion because of a pre-existing PD diagnosis.

Sleep disorders and an increased risk of Parkinson's disease in individuals with non-apnea sleep disorders: a population-based cohort study.

Sleep disorders are common non-motor symptoms in patients with Parkinson's disease. Our study aims to explore the relationship between non-apnea sleep disorders and future Parkinson's disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91273 adult patients who had non-apnea sleep disorders without pre-existing Parkinson's disease were enrolled. An age-, gender-, income-, urbanization- and Charlson comorbidity index score-matched control cohort consisting of 91273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinson's disease, death or until the end of 2010, whichever came first. The Kaplan-Meier analyses revealed patients with non-apnea sleep disorders tended to develop Parkinson's disease (log-rank test, P<0.001). After a multivariate adjustment in a Cox regression model, non-apnea sleep disorders was an independent risk factor for the development of Parkinson's disease [crude hazard ratio: 1.63, 95% confidence interval (CI): 1.54-1.73, P<0.001; adjusted hazard ratio: 1.18, 95% CI: 1.11-1.26, P<0.001]. In the subgroup analysis, patients with chronic insomnia (lasting more than 3months) had the greatest risk (crude hazard ratio: 2.91, 95% CI: 2.59-3.26, P<0.001; adjusted hazard ratio: 1.37, 95% CI: 1.21-1.55, P<0.001). In conclusion, this study revealed that non-apnea sleep disorders, especially chronic insomnia, are associated with a higher risk for future Parkinson's disease.

Naloxone‐responsive acute dystonia and parkinsonism following general anaesthesia

Various movement disorders such as dystonia may acutely develop during or at emergence from general anaesthesia in patients with or without pre-existing Parkinson disease. These movements are triggered by a variety of drugs including propofol, sevoflurane, anti-emetics, antipsychotics and opioids. The postulated mechanism involves an imbalance between dopaminergic and cholinergic neurotransmitters in the basal ganglia. We report an acute, severe and generalised dystonic reaction in an otherwise healthy woman at emergence from general anaesthesia, dramatically reversed by the administration of naloxone, pointing to a potential role of the fentanyl and morphine that the patient had received. Recent literature on the mechanisms of abnormal movements induced by opioids are discussed. The severity of the reaction with usual doses of opioids, in a patient with no prior history of parkinsonism, led to further investigation that demonstrated the possibility of an enhanced susceptibility to opioids, involving a genetically determined abnormal function of glycoproteine-P and catechol-O-methyltransferase.

Bilateral chronic subdural haematoma: a reversible cause of parkinsonism

Elderly patients with chronic subdural haematoma most commonly present with altered mental status and focal neurological deficit.1 New onset parkinsonism and worsening of pre-existing Parkinson's disease are both uncommon but recognized presenting features of chronic subdural haematoma.2-5

Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature.

There is no clear consensus regarding the frequency (and hence, the risk), of dyskinesias or motor fluctuations during chronic levodopa therapy for Parkinson's disease (PD). Multiple clinical series have tabulated these frequencies since the advent of levodopa over 30 years ago. We were interested in determining: (1) the aggregate frequency figures in the existing literature; and (2) how clinical series from the early levodopa era, which included patients with longer durations of parkinsonism, compare to more recent (modern era) series. We searched MEDLINE for all English language publications reporting the cumulative frequency of levodopa-induced dyskinesias or motor fluctuations during discrete intervals of treatment. This generated 2,478 publications spanning 1966 through September 2000. Papers with appropriate titles or abstracts were reviewed; reference lists from published clinical series were a source of additional papers for review. This ultimately yielded 74 publications with adequate data, relating to 112 intervals of levodopa treatment. Series that included patients with PD-onset well before levodopa availability (pre-levodopa era) were separately analyzed from all subsequent series. Series were grouped by duration of levodopa therapy and the median frequencies of dyskinesias and motor fluctuations were tabulated for each group. The data were analyzed both with and without adjustment for the number (N) in each series. Among series containing pre-levodopa era patients, the median dyskinesia frequency was already 50% by 5-6 months of treatment. This contrasts with the modern era series where dyskinesias were reported later in treatment. The median dyskinesia frequency was slightly less than 40% by 4-6 years of levodopa therapy among modern era patients. Motor fluctuations (wearing-off) were not tabulated in most of the early levodopa series. Among modern era reports, motor fluctuations were nil during the first year of levodopa therapy but were experienced by approximately 40% of patients by 4-6 years of treatment. Similar results were found when the analyses were restricted to only prospective studies where levodopa motor complications were targeted outcome measures. The conclusions reached were: (1) patients from the pre-levodopa era experienced dyskinesias much earlier during levodopa treatment than modern era patients, perhaps because of longer durations of pre-existing PD; (2) in the present era, patients treated with levodopa therapy for 4-6 years have approximately a 40% likelihood of experiencing motor fluctuations and a risk of dyskinesias just short of 40%; and (3) these findings represent incident data and the prevalence of clinically important morbidity may be substantially less.

Extrapyramidal Side-Effects in Elderly Patients Exposed to Selective Serotonin Reuptake Inhibitors

Extrapyramidal side-effects (EPSE) are reported to occur in less than one per 1000 patients treated with selective serotonin reuptake inhibitors (SSRIs). However, it might be expected that EPSE might occur more frequently in elderly patients. We assessed the case notes of all elderly patients admitted to an acute psychiatric unit over a 3-year period and the charts of an equivalent number of elderly patients seen by a geriatric psychiatry consultation/liaison team on the general hospital's medical wards to determine the prevalence of EPSE following exposure to SSRIs. Records from 136 admissions and 140 consultations were assessed. A total of 67 patients were prescribed an SSRI. Four patients (6 per cent) developed an extrapyramidal reaction, two of whom had pre-existing Parkinson's disease, and all of whom came from the medically ill consultation group. In each case the adverse effect resolved completely after discontinuation of the SSRI. The prevalence of SSRI-associated EPSE may be higher in the elderly, and in particular in medically ill patients with underlying brain disease. © 1997 by John Wiley & Sons, Ltd.