<b><i>Introduction:</i></b> Herpesviruses might play a role in the pathogenesis of neurodegenerative disorders. We sought to examine a possible association between alpha herpesvirus infections and Parkinson’s disease. <b><i>Methods:</i></b> We conducted a population-based case-control study of incident Parkinson’s disease in 2009 Medicare beneficiaries age 66–90 years (89,790 cases, 118,095 randomly selected comparable controls). We classified beneficiaries with any diagnosis code for “herpes simplex” and/or “herpes zoster” in the previous 5 years as having had the respective alpha herpesviruses. In beneficiaries with Part D prescription coverage, we also identified those prescribed anti-herpetic medications. We calculated odds ratios (OR) and 95% CI between alpha herpesvirus diagnosis/treatment and Parkinson’s disease with logistic regression, with adjustment for age, sex, race/ethnicity, smoking, and use of medical care. <b><i>Results:</i></b> Parkinson’s disease risk was inversely associated with herpes simplex (OR 0.79, 95% CI 0.74–0.84), herpes zoster (OR 0.88, 95% CI 0.85–0.91), and anti-herpetic medications (OR 0.87, 95% CI 0.80–0.96). <b><i>Conclusion:</i></b> Herpesvirus infection or treatment might reduce risk of Parkinson’s disease, but future studies will be required to explore whether this inverse association is causal.

Background-Well water frequently is considered a risk factor for Parkinson disease (PD), but few studies were designed appropriately to test whether geographic factors affect PD risk. Objective-To determine the risk of PD in relation to residential use of private well water. Methods-In a nationwide, population-based case-control study, we identified all incident PD cases (N=89,790) and all comparable controls (N=21,549,400) age 66-90 who solely relied on Medicare coverage in the U.S. in 2009. We estimated the probability of use of private well water using zip code of residence at diagnosis/reference and U.S. Census data on household water source. We modeled this exposure linearly in logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI) of PD risk in relation to well water use. We adjusted for age, sex and race/ethnicity, and verified that smoking and use of medical care did not confound results. We repeated analyses with a 2-year exposure lag and separately within each U.S. state. Results-Use of well water was inversely associated with PD risk (OR=0.87, 95% CI 0.85-0.89). We confirmed this association in a Cox survival analysis in which we followed controls for 5 years, death or PD diagnosis. There was little evidence that well water use increased risk of PD in any individual state. Conclusions-Although it remains possible that exposures in well water in more narrow geographic regions increase PD risk, in general these results suggest that exposures more common in urban/suburban areas might also be relevant.

Parkinson disease (PD) has a relatively long prodromal period that may permit early identification to reduce diagnostic testing for other conditions when patients are simply presenting with early PD symptoms, as well as to reduce morbidity from fall-related trauma. Earlier identification also could prove critical to the development of neuroprotective therapies. We previously developed a PD predictive model using demographic and Medicare claims data in a population-based case-control study. e area under the receiver-operating characteristic curve (AUC) indicated good performance. We sought to further validate this PD predictive model. In a randomly selected, population-based cohort of 115,492 Medicare beneficiaries aged 66-90 and without PD in 2009, we applied the predictive model to claims data from the prior five years to estimate the probability of future PD diagnosis. During five years of follow-up, we used 2010-2014 Medicare data to determine PD and vital status and then Cox regression to investigate whether PD probability at baseline was associated with time to PD diagnosis. Within a nested case-control sample, we calculated the AUC, sensitivity, and specificity. A total of 2,326 beneficiaries developed PD. Probability of PD was associated with time to PD diagnosis (p < 0.001, hazard ratio � 13.5, 95% confidence interval (CI) 10.6-17.3 for the highest vs. lowest decile of probability). e AUC was 83.3% (95% CI 82.5%-84.1%). At the cut point that balanced sensitivity and specificity, sensitivity was 76.7% and specificity was 76.2%. In an independent sample of additional Medicare beneficiaries, we again applied the model and observed good performance (AUC � 82.2%, 95% CI 81.1%-83.3%). Administrative claims data can facilitate PD identification within Medicare and Medicare-aged samples.

Introduction/Aims: We investigated the age-and sex-specific incidence and survival of Medicare beneficiaries with amyotrophic lateral sclerosis (ALS) in patients 66 to 90 years of age. Methods:We identified all incident ALS cases within a population-based sample of Medicare beneficiaries in 2009 (total: 22 000 177 person-years at risk for ALS). We calculated age-and sex-specific incidence in 2009 according to multiple, progressively more stringent case definitions. Our most inclusive definition required one ALS code, whereas the most restrictive definition required at least one additional ALS code more than 6 months after the first code, including one from a neurologist. We identified associated imaging studies and electrodiagnostic testing and followed all cases through the end of 2014 to determine survival. Results:The overall incidence for our most inclusive definition was 22.84 per 100 000 person-years for men and 16.05 per 100 000 person-years for women. The overall incidence was 5.72 per 100 000 person-years for men and 3.99 per 100 000 person-years for women for our most restrictive definition. For our most inclusive definition, fewer than 39.7% of cases ever had an ALS diagnosis from a neurologist, more than 50% had an electrodiagnostic test or imaging study, and 40.1% survived less than 1 year after diagnosis, with 25.5% of these cases surviving no more than 6 months. Cases not meeting the most restrictive definition were more likely than those who did meet the restrictive definition to be older, black, or Asian.Discussion: The oldest and marginalized Medicare beneficiaries diagnosed with ALS are less likely to be included in epidemiological studies with restrictive definitions, but future studies will need to assess the accuracy of diagnosis.

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