Optimizing the electronic medical record to improve patient care and conduct quality improvement initiatives in a concussion specialty clinic.

Objective: To use the electronic medical record (EMR) to optimize patient care, facilitate documentation, and support quality improvement and practice-based research in a concussion (mild traumatic brain injury; mTBI) clinic.Methods: We built a customized structured clinical documentation support (SCDS) toolkit for patients in a concussion specialty clinic. The toolkit collected hundreds of fields of discrete, standardized data. Autoscored and interpreted score tests include the Generalized Anxiety Disorder 7-item scale, Center for Epidemiology Studies Depression scale, Insomnia Severity Index, and Glasgow Coma Scale. Additionally, quantitative score measures are related to immediate memory, concentration, and delayed recall. All of this data collection occurred in a standard appointment length.Results: To date, we evaluated 619 patients at an initial office visit after an mTBI. We provided a description of our toolkit development process, and a summary of the data electronically captured using the toolkit.Conclusions: The electronic medical record can be used to effectively structure and standardize care in a concussion clinic. The toolkit supports the delivery of care consistent with Best Practices, provides opportunities for point of care decision support, and writes comprehensive progress notes that can be communicated to other providers.

Design and Implementation of Structured Clinical Documentation Support Tools for Treating Stroke Patients.

BACKGROUND AND PURPOSE: Standardized electronic medical record tools provide an opportunity to efficiently provide care that conforms to Best Practices and supports quality improvement and practice-based research initiatives. METHODS: We describe the development of a customized structured clinical documentation "toolkit" that standardizes patient data collection to conform to Best Practices for treating patients with stroke. The toolkit collects patients' demographic information, relevant score test measures, and captures information on disability, treatment, and outcomes. RESULTS: We describe here our creation and implementation of the toolkits and provide example screenshots. As of August 1, 2018, we have evaluated 2332 patients at an initial visit for a possible stroke. We provide basic descriptive data gathered from the use of the toolkits, demonstrating their utility in collecting patient data in a manner that supports both quality clinical care and research initiatives. CONCLUSIONS: We have developed an EMR toolkit to support Best Practices in the care of patients with stroke. We discuss quality improvement projects and current research initiatives using the toolkit. This toolkit is being shared with other Departments of Neurology as part of the Neurology Practice-Based Research Network.

Mendelian randomization of serum urate and parkinson disease progression.

OBJECTIVE: Higher serum urate concentrations predict more favorable prognosis in individuals with Parkinson disease (PD). The purpose of this study was to test the causality of this association using a Mendelian randomization approach. METHODS: The study was conducted among participants in DATATOP and PRECEPT, 2 randomized trials among patients with early PD. The 808 patients with available DNA were genotyped for 3 SLC2A9 single nucleotide polymorphisms (SNPs) that identify an allele associated with lower urate concentrations, and for selected SNPs in other genes encoding urate transporters that have modest or no effect on serum urate levels. An SLC2A9 score was created based on the total number of minor alleles at the 3 SLC2A9 loci. Primary outcome was disability requiring dopaminergic treatment. RESULTS: Serum urate concentrations were 0.69mg/dl lower among individuals with ≥4 SLC2A9 minor alleles as compared to those with ≤2 (p = 0.0002). The hazard ratio (HR) for progression to disability requiring dopaminergic treatment increased with increasing SLC2A9 score (HR = 1.16, 95% confidence interval [CI] = 1.00-1.35, p = 0.056). In a comparative analysis, the HR was 1.27 (95% CI = 1.00-1.61, p = 0.0497) for a 0.5mg/dl genetically conferred decrease in serum urate, and 1.05 (95% CI = 1.01-1.10, p = 0.0133) for a 0.5mg/dl decrease in measured serum urate. No associations were found between polymorphisms in other genes associated with urate that do not affect serum urate and PD progression. INTERPRETATION: This Mendelian randomization analysis adds to the evidence of a causal protective effect of high urate levels.

Epstein-Barr virus neutralizing antibody levels and risk of multiple sclerosis.

Previous infection with Epstein-Barr virus (EBV) and infectious mononucleosis are established multiple sclerosis (MS) risk factors, and elevated serum titers of anti-EBV nuclear antigen (anti-EBNA) antibodies in healthy adults are strongly correlated with future MS risk. In this prospective study, we investigated the association between EBV neutralizing antibodies and MS risk. MS risk tended to be higher in individuals with high titers of neutralizing antibodies compared to those with low titers (relative risk [RR] = 2.2, 95% confidence interval [CI] 0.97-5.1). This association was attenuated after adjustment for anti-EBNA1 IgG Ab titers (RR = 1.4, 95% CI 0.5-3.5). This preliminary finding warrants further study in a larger population.

Standardizing Care of Neuro-oncology Patients Using a Customized Electronic Medical Record Toolkit.

OBJECTIVE: To develop and implement a customized toolkit within the electronic medical record (EMR) to standardize care of patients with brain tumors. PATIENTS AND METHODS: We built a customized structured clinical documentation support toolkit to capture standardized data at office visits. We detail the process by which this toolkit was conceptualized and developed. Toolkit development was a physician-led process to determine a work flow and necessary elements to support best practices as defined by the neuro-oncology clinical team. RESULTS: We have developed in our EMR system a customized work flow for clinical encounters with neuro-oncology patients. In addition to providing a road map for clinical care by our neuro-oncology team, the toolkit is designed to maximize discrete data capture. Several hundred fields of discrete data are captured through the toolkit in the context of our routine office visits. We describe the characteristics of patients seen at our clinic, the adoption of the toolkit, current initiatives supported by the toolkit, and future applications. CONCLUSION: The EMR can be effectively structured to standardize office visits and improve discrete data capture. This toolkit can be leveraged to support quality improvement and practice-based research initiatives at the point of care in a neuro-oncology practice.

Calcium channel blocker use and risk of Parkinson's disease.

We investigated whether the use of calcium channel blockers (CCBs) was associated with a reduced risk of Parkinson's disease (PD) in two large prospective cohorts: the Nurses' Health Study (NHS) and Health Professionals' Follow-Up Study (HPFS). Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) to assess the association between use of CCBs and risk of PD adjusting for potential confounders. We identified 514 incident cases of PD during follow-up. No association between baseline use of CCBs (RR = 1.18, 95% CI: 0.73-1.92), frequency of use or duration of use of CCBs and PD risk was observed (P > 0.2 for all). These findings do not support a role for CCBs in providing neuroprotection against development of PD.

Longitudinal Monitoring of Parkinson's Disease in Different Ethnic Cohorts: The DodoNA and LONG-PD Study.

Background: Different factors influence severity, progression, and outcomes in Parkinson's disease (PD). Lack of standardized clinical assessment limits comparison of outcomes and availability of well-characterized cohorts for collaborative studies. Methods: Structured clinical documentation support (SCDS) was developed within the DNA Predictions to Improve Neurological Health (DodoNA) project to standardize clinical assessment and identify molecular predictors of disease progression. The Longitudinal Clinical and Genetic Study of Parkinson's Disease (LONG-PD) was launched within the Genetic Epidemiology of Parkinson's disease (GEoPD) consortium using a Research Electronic Data Capture (REDCap) format mirroring the DodoNA SCDS. Demographics, education, exposures, age at onset (AAO), Unified Parkinson's Disease Rating Scale (UPDRS) parts I-VI or Movement Disorders Society (MDS)-UPDRS, Montreal Cognitive Assessment (MoCA)/Short Test of Mental Status (STMS)/Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Epworth Sleepiness Scale (ESS), dopaminergic therapy, family history, nursing home placement, death and blood samples were collected. DodoNA participants (396) with 6 years of follow-up and 346 LONG-PD participants with up to 3 years of follow-up were analyzed using group-based trajectory modeling (GBTM) focused on: AAO, education, family history, MMSE/MoCA/STMS, UPDRS II-II, UPDRS-III tremor and bradykinesia sub-scores, Hoehn and Yahr staging (H&Y) stage, disease subtype, dopaminergic therapy, and presence of autonomic symptoms. The analysis was performed with either cohort as the training/test set. Results: Patients are classified into slowly and rapidly progressing courses by AAO, MMSE score, H &Y stage, UPDRS-III tremor and bradykinesia sub-scores relatively early in the disease course. Late AAO and male sex assigned patients to the rapidly progressing group, whereas tremor to the slower progressing group. Classification is independent of which cohort serves as the training set. Frequencies of disease-causing variants in LRRK2 and GBA were 1.89 and 2.96%, respectively. Conclusions: Standardized clinical assessment provides accurate phenotypic characterization in pragmatic clinical settings. Trajectory analysis identified two different trajectories of disease progression and determinants of classification. Accurate phenotypic characterization is essential in interpreting genomic information that is generated within consortia, such as the GEoPD, formed to understand the genetic epidemiology of PD. Furthermore, the LONGPD study protocol has served as the prototype for collecting standardized phenotypic information at GEoPD sites. With genomic analysis, this will elucidate disease etiology and lead to targeted therapies that can improve disease outcomes.

Quality improvement and practice-based research in sleep medicine using structured clinical documentation in the electronic medical record.

BACKGROUND: We developed and implemented a structured clinical documentation support (SCDS) toolkit within the electronic medical record, to optimize patient care, facilitate documentation, and capture data at office visits in a sleep medicine/neurology clinic for patient care and research collaboration internally and with other centers. METHODS: To build our SCDS toolkit, physicians met frequently to develop content, define the cohort, select outcome measures, and delineate factors known to modify disease progression. We assigned tasks to the care team and mapped data elements to the progress note. Programmer analysts built and tested the SCDS toolkit, which included several score tests. Auto scored and interpreted tests included the Generalized Anxiety Disorder 7-item, Center for Epidemiological Studies Depression Scale, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index, and the International Restless Legs Syndrome Study Group Rating Scale. The SCDS toolkits also provided clinical decision support (untreated anxiety or depression) and prompted enrollment of patients in a DNA biobank. RESULTS: The structured clinical documentation toolkit captures hundreds of fields of discrete data at each office visit. This data can be displayed in tables or graphical form. Best practice advisories within the toolkit alert physicians when a quality improvement opportunity exists. As of May 1, 2019, we have used the toolkit to evaluate 18,105 sleep patients at initial visit. We are also collecting longitudinal data on patients who return for annual visits using the standardized toolkits. We provide a description of our development process and screenshots of our toolkits. CONCLUSIONS: The electronic medical record can be structured to standardize Sleep Medicine office visits, capture data, and support multicenter quality improvement and practice-based research initiatives for sleep patients at the point of care.

Reproductive factors, exogenous estrogen use, and risk of Parkinson's disease.

To determine if reproductive factors or exogenous estrogen are associated with risk of Parkinson's disease (PD), we conducted a prospective study with 22 years of follow-up among postmenopausal participants in the Nurses' Health Study. Relative risks (RRs) and 95% confidence intervals (CIs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. Risk of PD was not significantly associated with any of the reproductive factors measured or exogenous estrogen use. Use of postmenopausal hormones, however, may modify the associations of smoking and caffeine intake with PD risk. The inverse relation between smoking and PD risk was attenuated among ever users of postmenopausal hormones (P for interaction = 0.05). Similar results were obtained for caffeine (P for interaction = 0.09). In exploratory analyses, women using progestin-only hormones were found to have an increased PD risk, but this result was based on a very small number of cases (n = 4). In this large longitudinal study, we found no evidence of a beneficial effect of exogenous or endogenous estrogens on risk of PD. The use of postmenopausal hormone use may interact with other risk factors, but findings are preliminary and need confirmation in other populations.

Building of EMR Tools to Support Quality and Research in a Memory Disorders Clinic.

The electronic medical record (EMR) presents an opportunity to standardize patient data collection based on quality guidelines and conduct practice-based research. We describe the development of a customized EMR "toolkit" that standardizes patient data collection with hundreds of discrete fields that supports Best Practices for treating patients with memory disorders. The toolkit also supports practice-based research. We describe the design and successful implementation of a customized EMR toolkit to support Best Practices in the care of patients with memory disorders. We discuss applications, including quality improvement projects and current research initiatives, using the toolkit. This toolkit is being shared with other departments of Neurology as part of the Neurology Practice-Based Research Network. Data collection is ongoing, including longitudinal follow-up. This toolkit will generate data that will allow for descriptive and hypothesis driven research as well-quality improvement among patients seen in a memory clinic.

Factors Affecting Cognition and Depression in Adult Patients with Epilepsy.

BACKGROUND AND PURPOSE: Epilepsy patients are more likely to experience depressive symptoms and cognitive impairment compared to individuals in the general population. As the reasons for this are not definitively known, we sought to determine what factors correlate most strongly with cognition and a screening test for depression in epilepsy patients. METHODS: Our study population included 379 adult patients diagnosed with epilepsy or seizure in our neurology clinic. We collected detailed demographic and clinical data during patient visits using structured clinical documentation support tools that we have built within our commercial electronic medical records system (Epic), including a depression score (Neurological Disorders Depression Inventory for Epilepsy, NDDIE) and cognition score test measures (specifically in this study, Mini-Mental State Examination [MMSE]). Medication, age, gender, body mass index, duration of epilepsy, seizure frequency, current number of anti-epileptic medications, years of education were assessed in relation to baseline score as well as change in score from initial visit to first annual follow-up. RESULTS: Of the analyzed factors, two statistically significant associations were found after correction for multiple testing. Male gender and lower anti-seizure medication count were associated with better mood, as assessed by NDDIE score, at initial visit. Specifically, male gender was associated with a 1.3 decrease in NDDIE and for each additional anti-seizure medication, there was an associated 1.2 increase in NDDIE. CONCLUSIONS: However, these factors were not associated with change in NDDIE score from initial to first annual follow-up visit. These findings, although interesting, are preliminary. Additionally, these findings were based on a homogenous (mainly Caucasian) clinic-based population and detailed information on previous medication use was lacking. Further work is needed to replicate these findings and to understand any mechanisms that may explain these associations.

Use of an Electronic Medical Record to Track Adherence to the Mediterranean Diet in a US Neurology Clinical Practice.

OBJECTIVE: We describe our experience with routinely capturing and analyzing Mediterranean diet data via structured clinical documentation support tools built into the electronic medical record and describe adherence to the Mediterranean diet in patients at risk for either stroke or dementia in a US neurology clinical practice. PATIENTS AND METHODS: The Mediterranean diet is associated with a reduced risk of stroke and dementia. The Department of Neurology at NorthShore University HealthSystem routinely evaluates patients at initial and annual outpatient visits using structured clinical documentation support (SCDS) tools built into the electronic medical record (EMR). For patient evaluations in our Vascular Neurology and Brain Health subspecialty clinics, SCDS tools in the EMR include the validated 14-item questionnaire for Mediterranean diet adherence (PREvención con DIeta MEDiterránea [PREDIMED]) that autoscores, auto-interprets, writes to the progress note, and electronically captures data. Our study population includes patients seen at these clinics from July 1, 2015, through November 29, 2017. RESULTS: At their initial office visit, 25.5% (95/373) of Brain Health patients scored 10 or more points ("strongly adherent") on the PREDIMED (median, 8; range, 0-14) whereas 6.7% (55/829) of Vascular Neurology patients achieved a score of 10 or more points (median, 6; range, 0-12). By contrast, 34.7% (2586/7447) of individuals in the original PREDIMED cohort were strongly adherent to the Mediterranean diet. CONCLUSION: PREDIMED scores can be electronically captured to tailor nutrition interventions by assessing baseline adherence at the time of their initial neurology clinic visit. Patients in our Midwestern US clinics were weakly adherent to the Mediterranean diet. This suggests a major opportunity for nutrition intervention and education in US neurology clinical practices, toward preserving and improving brain health.

Design and implementation of pragmatic clinical trials using the electronic medical record and an adaptive design.

OBJECTIVES: To demonstrate the feasibility of pragmatic clinical trials comparing the effectiveness of treatments using the electronic medical record (EMR) and an adaptive assignment design. METHODS: We have designed and are implementing pragmatic trials at the point-of-care using custom-designed structured clinical documentation support and clinical decision support tools within our physician's typical EMR workflow. We are applying a subgroup based adaptive design (SUBA) that enriches treatment assignments based on baseline characteristics and prior outcomes. SUBA uses information from a randomization phase (phase 1, equal randomization, 120 patients), to adaptively assign treatments to the remaining participants (at least 300 additional patients total) based on a Bayesian hierarchical model. Enrollment in phase 1 is underway in our neurology clinical practices for 2 separate trials using this method, for migraine and mild cognitive impairment (MCI). RESULTS: We are successfully collecting structured data, in the context of the providers' clinical workflow, necessary to conduct our trials. We are currently enrolling patients in 2 point-of-care trials of non-inferior treatments. As of March 1, 2018, we have enrolled 36% of eligible patients into our migraine study and 63% of eligible patients into our MCI study. Enrollment is ongoing and validation of outcomes has begun. DISCUSSION: This proof of concept article demonstrates the feasibility of conducting pragmatic trials using the EMR and an adaptive design. CONCLUSION: The demonstration of successful pragmatic clinical trials based on a customized EMR and adaptive design is an important next step in achieving personalized medicine and provides a framework for future studies of comparative effectiveness.

Long polymerase chain reaction-based fluorescence in situ hybridization analysis of female carriers of X-linked chronic granulomatous disease deletions.

Chronic granulomatous disease (CGD) is a rare inherited disorder in which antimicrobial activity of phagocytes is impaired due to the lack of reactive oxygen species, or oxidative burst, produced by NADPH oxidase. The X-linked form of CGD, representing approximately 70% of all cases, is caused by mutations in the cytochrome b beta subunit (CYBB) gene, which maps to chromosome Xp21.1. CYBB encodes the gp91-phox protein, a necessary component in the NADPH oxidase pathway. A wide variety of mutations have been identified in X-linked CGD patients, all of which lead to deletion of the functional protein and no oxidative burst activity. The mutations vary from single nucleotide substitutions to deletions of the entire gene. In this article, we report a mutation detection method for probands of female relatives at risk for carrier status of large deletions of the CYBB gene. Through fluorescent in situ hybridization of metaphase chromosomes, we were able to consistently distinguish carriers from noncarriers using polymerase chain reaction-derived, labeled DNA specific for exons 2 to 13 of the CYBB region at Xp21.1.

The human ovarian teratocarcinoma cell line PA-1 demonstrates a single translocation: analysis with fluorescence in situ hybridization, spectral karyotyping, and bacterial artificial chromosome microarray.

Cell lines derived from tumors contain numerous chromosomal aberrations and are the focus of study in tumor evolution. The ovarian teratocarcinoma cell line PA-1 demonstrates a single chromosomal aberration: a reciprocal t(15;20)(p11.2;q11.2). A complete molecular genetic analysis was undertaken to characterize this cell line. The PA-1 cell line was studied with fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), bacterial artificial chromosome (BAC) microarray, and Western blotting. Amplification of 20q is frequently implicated in both breast and ovarian cancer; this region contains a number of oncogenes including MDM2, ZNF217, and the ovarian tumor marker WFDC2 (alias HE4). FISH revealed gene amplification of AIB1 (now known as NCOA3) but not STK15 (now known as AURKA). Immunoblot analysis demonstrated 3.6-fold overexpression of the AIB1 protein product, but no elevation of the STK15. BAC cancer gene microarray analysis showed gene amplification of > or =1.20 for five oncogenes. The presence of a consistent single change in PA-1, the t(15;20)(p11.2;q11.2), suggests that the aberration is significant with respect to the transformation status of the cell line. This translocation appears to cause overexpression of AIB1 (and perhaps other proteins), which may provide an immortalizing effect on this cell line.

Vitamin D as an early predictor of multiple sclerosis activity and progression.

IMPORTANCE: It remains unclear whether vitamin D insufficiency, which is common in individuals with multiple sclerosis (MS), has an adverse effect on MS outcomes. OBJECTIVES: To determine whether serum concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, predict disease activity and prognosis in patients with a first event suggestive of MS (clinically isolated syndrome). DESIGN, SETTING, AND PARTICIPANTS: The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a randomized trial originally designed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinically isolated syndrome. Serum 25(OH)D concentrations were measured at baseline and 6, 12, and 24 months. A total of 465 of the 468 patients randomized had at least 1 25(OH)D measurement, and 334 patients had them at both the 6- and 12-month (seasonally asynchronous) measurements. Patients were followed up for 5 years clinically and by magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: New active lesions, increased T2 lesion volume, and brain volume on magnetic resonance imaging, as well as MS relapses and disability (Expanded Disability Status Scale score). RESULTS: Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression. A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions (P < .001), 57% lower relapse rate (P = .03), 25% lower yearly increase in T2 lesion volume (P < .001), and 0.41% lower yearly loss in brain volume (P = .07) from months 12 to 60. Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60. In analyses using dichotomous 25(OH)D levels, values greater than or equal to 50 nmol/L (20 ng/mL) at up to 12 months predicted lower disability (Expanded Disability Status Scale score, -0.17; P = .004) during the subsequent 4 years. CONCLUSIONS AND RELEVANCE: Among patients with MS mainly treated with interferon beta-1b, low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression.

XVI European Charcot Foundation lecture: nutrition and environment: can MS be prevented?

Multiple sclerosis (MS) is a relatively common debilitating neurologic disease that affects people in early adulthood. While the characteristic pathology of MS has been well described, the etiology of the disease is not well understood, despite decades of research and the identification of strong genetic and environmental candidates for susceptibility. A question central to all diseases, but posed specifically for MS at the XVI European Charcot Foundation Lecture, was 'Can MS be prevented?' To address this question, we have evaluated the available data regarding nutritional and environmental factors that may be related to MS susceptibility and suggest the extent to which a potential intervention may reduce disease burden. It is our opinion that intervention, particularly supplementation with vitamin D, could have a dramatic impact on disease prevalence. Understanding that any intervention or behavioral modification will surely act in the context of genetic susceptibility and unidentified stochastic events, it is likely that not all MS is 'preventable'. Epidemiologic observation has provided key insights into environmental and nutritional factors that may alter one's susceptibility to MS, however, there are still many questions in unraveling the etiology of this complex disease.

Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis.

Risk of multiple sclerosis (MS) decreases with increasing plasma levels of 25-hydroxyvitamin D [25(OH)D]. If this association reflected a protective effect of vitamin D, MS risk should be lower among individuals carrying genetic variants that predict high 25(OH)D levels. The aim of the study was to determine whether individuals with genotypes predicting higher 25(OH)D levels have decreased MS risk. Logistic regression was used to assess the association between single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels and MS risk in 1,655 cases and 6,349 controls. Analyses were further stratified by HLA-DR15 status, assessed by genotyping a single SNP strongly correlated with the HLA DRB1 1501 risk haplotype, and complemented by considering a SNP near CYP27B1. SNPs in GC were predictors of 25(OH)D levels, but not MS risk, in either HLA-DR15 negative or HLA-DR15 positive individuals. In contrast, there was a suggestion of a difference in the effect of a CYP2R1 allele dependent on HLA-DR15 genotype. The 'A' allele of CYP2R1 rs10741657 was associated with increased 25(OH)D levels and a non-significant reduced MS risk among HLA-DR15 negative (OR = 0.89, 95% CI: 0.79, 1.01) that was not apparent in HLA-DR15 positive individuals. The 'C' allele of CYP27B1 rs703842 was inversely associated with MS risk; this association appeared stronger among HLA-DR15 negative (OR = 0.79, 95% CI: 0.69, 0.90) compared to HLA-DR15 positive individuals (OR = 0.91, 95% CI: 0.80, 1.04). This preliminary finding suggests the possibility that the putative beneficial effect of vitamin D on MS risk maybe attenuated in individuals carrying the HLA-DR15 MS risk allele.

Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease.

OBJECTIVE: To determine whether history of hypertension, hypercholesterolemia, or diabetes is associated with risk of Parkinson disease (PD). METHODS: Prospective study among participants in two large cohorts: the Nurses' Health Study (121,046 women) and the Health Professionals Follow-up Study (50,833 men). Mean duration of follow-up was 22.9 years in women, aged 30 to 55 years at baseline, and 12.6 years in men, aged 40 to 75 years at baseline. Relative risks (RRs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. RESULTS: We identified a total of 530 incident cases of PD during the follow-up. Risk of PD was not associated with self-reported history of hypertension (RR = 0.96, 95% CI = 0.80 to 1.15), high cholesterol (RR = 0.98, 95% CI = 0.82 to 1.19), or diabetes (RR = 1.04, 95% CI = 0.74 to 1.46), after adjusting for age and smoking in pack-years. Risk of PD decreased modestly with increasing levels of self-reported total cholesterol (RR for a 50-mg/dL increase in total cholesterol = 0.86, 95% CI = 0.78 to 0.95, p for trend = 0.02), but use of cholesterol-lowering drugs was not associated with PD risk (RR comparing users with nonusers = 0.85, 95% CI = 0.59 to 1.23). Among individuals with PD, systolic blood pressure was similar to noncases up to the time of diagnosis but declined afterward. CONCLUSIONS: Results of this large prospective study suggest that Parkinson disease risk is not significantly related to history of hypertension, hypercholesterolemia, or diabetes but may modestly decline with increasing blood cholesterol levels.