Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study.
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ABSTRACT: Objective
To examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease.Methods
One hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality.Results
The standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50-2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive supranuclear palsy) had the highest mortality. In early Parkinson disease, a mild cognitive impairment diagnosis, freezing of gait, hyposmia, reduced dopamine transporter activity in the caudate, and elevated leukocytes in the CSF were significantly associated with shorter survival.Conclusion
Although patients presenting with idiopathic parkinsonism have reduced survival, the survival is highly dependent on the type and characteristics of the parkinsonian disorder. Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy. The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implications.
SUBMITTER: Backstrom D
PROVIDER: S-EPMC6282235 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionPatients with Parkinson disease (PD) tend to have ophthalmic symptoms. Retinal diseases are associated with central nervous system diseases, especially neurodegenerative diseases. Here, we investigated the association of retinal diseases with PD, especially the temporal relationship before and after PD diagnosis.MethodsData were obtained from the National Health Insurance Research Database of Taiwan. In total, 21,845 patients with newly diagnosed PD were matched with four controls each on the basis of propensity score. This study was bidirectional. A case-control study evaluated the adjusted odds ratio (aOR) of retinal disease before PD diagnosis by using conditional logistic regression. Furthermore, a cohort study evaluated the adjusted subdistribution hazard ratio (aSHR) for new-onset retinal and optic nerve diseases after PD diagnosis by using competing risk analysis. The association between PD with optic nerve diseases and glaucoma (another common ophthalmic diseases with the consequence of retinal dysfunction) were also analyzed as reference.ResultsIn the case-control study, PD was found to be significantly comorbid with recent and remote retinal disease [recent: ≤ 5 years, aOR: 1.12, 95% confidence interval (CI): 1.03-1.23; remote: > 5 years, aOR: 1.18, 95% CI: 1.04-1.34]. No similar association was identified between optic nerve disease or glaucoma with PD. In the cohort study, patients with PD were found to have a low risk of retinal disease in short-term (≤ 5 years, aSHR: 0.81, 95% CI: 0.71-0.93) and long-term (> 5 years, aSHR: 0.82, 95% CI: 0.72-0.93) follow-up.ConclusionThe study findings demonstrated that patients with prediagnostic PD were at greater risk of retinal disease than non-PD participants, but the risk reversed afterward. Thus, retinal disease may be a premotor manifestation of PD, and there may be some possible effect of dopamine supplements on retina.
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Project description:To determine the extent to which excess mortality after fractures attributable to particular causes at specific skeletal sites can be predicted using data about all medical diagnoses, we conducted a historical cohort study among 1991 Olmsted County, Minnesota, residents aged ? 50 years who experienced any fracture in 1989 to 1991 and who were followed passively for up to 22 years for death from any cause. We used a machine learning approach, gradient boosting machine (GBM) modeling, to determine whether the comorbid conditions present at the time of fracture and those that arose subsequently could, in aggregate, identify patients at the greatest increased risk of death. During 21,867 person-years of follow-up, 1245 deaths were observed when 1061 were expected (standardized mortality ratio, 1.2; 95% confidence interval [CI] 1.1-1.2). Patients presented with a median history of 26 comorbid conditions each as assessed by the Clinical Classification Software system and 57 each over the total duration of follow-up. Using all available information, the excess deaths could be predicted with good accuracy (c-index ? 0.80) in 89% of the GBM models built for patients with different types of fracture; in one-third of the models, the c-index was ? 0.90. The conditions most prominent in the GBM prediction models were also reflected in the specific causes of death that were elevated, suggesting the influence of confounding on the relationship. However, the predominant comorbid conditions were mainly those responsible for mortality in the general population, rather than the specific diseases most closely associated with secondary osteoporosis. To reduce long-term deaths in the fracture population as a whole, a more general approach to the fracture patient is indicated.
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Project description:ImportanceThe association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial.ObjectiveTo assess whether women who underwent premenopausal bilateral oophorectomy were at increased risk of parkinsonism and PD and whether the associations varied by age at oophorectomy and by receipt of estrogen replacement therapy.Design, setting, and participantsThis cohort study used data from a combination of 2 independent cohort studies, the Mayo Clinic Cohort Study of Oophorectomy and Aging 1 and 2, which were based on the Rochester Epidemiology Project medical records-linkage system. A population-based sample of 5499 women from Olmsted County, Minnesota, were included; of those, 2750 women underwent bilateral oophorectomy for a benign indication before spontaneous menopause between January 1, 1950, and December 31, 2007 (oophorectomy cohort), and 2749 age-matched women who did not undergo bilateral oophorectomy were randomly sampled from the general population (reference cohort). Data were analyzed from March 1 to April 30, 2022. The date of oophorectomy was considered the index date for both groups.ExposuresMedical record documentation of bilateral oophorectomy abstracted from a medical records-linkage system (Rochester Epidemiology Project).Main outcomes and measuresIncidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review.ResultsAmong 5499 participants (median [IQR] age, 45.0 [40.0-48.0] years; 5312 [96.6%] White), 2750 women (2679 White [97.4%]) underwent bilateral oophorectomy at a median age of 45.0 years (IQR, 40.0-48.0 years), and 2749 women (2633 White [95.8%]) with a median age of 45.0 years (IQR, 40.0-48.0 years) at the index date were included in the reference cohort. Bilateral oophorectomy was associated with an increased risk of parkinsonism overall (hazard ratio [HR], 1.59; 95% CI, 1.02-2.46) and in women younger than 43 years at oophorectomy (HR, 7.67; 95% CI, 1.77-33.27). There was a pattern of increasing risk with younger age at the time of oophorectomy using 4 age strata (≥50 years: HR, 1.43 [95% CI, 0.50-4.15]; 46-49 years: HR, 1.55 [95% CI, 0.79-3.07]; 40-45 years: HR, 1.36 [95% CI, 0.64-2.89]; <40 years: HR, 8.82 [95% CI, 1.08-72.00]; P = .02 for trend). The number needed to harm was 53 women overall and 27 women younger than 43 years at the time of oophorectomy. Bilateral oophorectomy was also associated with an increased risk of PD in women younger than 43 years at oophorectomy (HR, 5.00; 95% CI, 1.10-22.70), with a number needed to harm of 48 women. Among women who underwent oophorectomy at 45 years and younger, the risk was lower in women who received estrogen after the procedure and through age 50 years compared with women who did not. For parkinsonism, the HRs were 1.72 (95% CI, 0.54-5.53) vs 2.05 (95% CI, 0.80-5.23); for PD, the HRs were 1.53 (95% CI, 0.29-8.23) vs 2.75 (95% CI, 0.84-9.04). However, the differences were not significant.Conclusions and relevanceIn this study, premenopausal women who underwent bilateral oophorectomy before age 43 years had an increased risk of parkinsonism and PD compared with women who did not undergo bilateral oophorectomy. These findings suggest that a reduction in the practice of prophylactic bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have substantial benefit for reducing the risk of parkinsonism and PD.
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Project description:ObjectiveLeucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson disease (PD). Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein. Herein, we characterize the clinical and genetic features associated with Lrrk2 p.R1441C.MethodsWe identified 33 affected and 15 unaffected LRRK2 c.4321C>T (p.R1441C) mutation carriers through an international consortium originating from three continents. The age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis.ResultsThe clinical presentation of Lrrk2 p.R1441C carriers was similar to sporadic PD and Lrrk2 p.G2019S parkinsonism. The mean age at onset for parkinsonism was 60 years, range 30-79 years; fewer than 20% of the patients had symptoms before the age 50 years, while by 75 years >90% of them had developed symptoms. Haplotype analysis suggests four independent founders for the p.R1441C mutation.ConclusionsThe distribution in age at onset and clinical features in Lrrk2 p.R1441C patients are similar to idiopathic and Lrrk2 p.G2019S parkinsonism. Several independent founders of the p.R1441C substitution suggest this site is prone to recurrent mutagenesis.
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