Abstract
Objective
To determine Parkinson disease (PD) life expectancy in the United States and identify demographic, geographic and clinical factors that influence survival.
Design
Retrospective cohort study of 138,000 Medicare beneficiaries with incident PD were identified in 2002 and followed through 2008.
Main Outcome Measures
Confounder adjusted six year risk of death as influenced by three groups of factors: 1) race, sex, age at diagnosis 2) geography, environmental factors 3) clinical conditions. We examined hospitalization diagnoses in terminal PD, compared PD mortality to that of other common diseases.
Results
Thirty-five percent of PD cases lived more than six years. Sex and race significantly predicted survival: female (HR 0.74, 0.73– 0.75), Hispanic (HR 0.72, 0.65–0.80) and Asian (HR 0.86, 0.82–0.91) cases had a lower adjusted risk of death than white males. Dementia/cognitive impairment, diagnosed in 69.6% of cases, most often in Blacks (78.2%) and women (71.5%), was associated with a greater likelihood of death (HR 1.72, 1.69–1.75). PD cases had greater mortality than many common life threatening diseases. Terminal PD patients were hospitalized frequently for cardiovascular disease (15.06%) and infection (29.52%), rarely for PD related illness (4.2%). Regional survival rates were similar, but urban PD cases living in a high industrial metal emission area had a slightly higher adjusted risk of death (HR 1.19, 1.10–1.29).
Conclusions
Demographic and clinical factors impact PD survival. Dementia is highly prevalent in PD and is associated with a significant increase in mortality. More research is needed to understand if environmental exposures influence PD course or survival.
Introduction
Although Parkinson disease is a common neurodegenerative disease of the elderly, there are conflicting data on survival of PD patients. Some studies of incident PD mortality have suggested a higher risk of death when compared to the general population1–3, others have suggested no difference.4;5 Similarly, studies provide conflicting data on whether age at diagnosis or gender affects survival.6–12 Two administrative database studies used insurance claims13 and anti-parkinsonian drug prescription data14 to examine PD mortality, but included prevalent cases from ethnically homogenous populations, limiting the generalizability of their findings.15 Other studies were limited by exclusive case recruitment from specialty clinics or drug treatment trials. At the time of this study, there was no available survival data on PD cases diagnosed after 2000, population-based data from the U.S., nor detailed survival data on women and non-whites. In this nationwide retrospective cohort study, we examine the 6 year survival of incident Parkinson disease in the U.S. using Medicare claims data from over 36 million elderly Americans per year, and broadly investigate mortality and survival in PD using the largest cohort to date.
In addition to detailed demographic analyses of PD survival, we have performed several unique PD mortality investigations. It is unclear why PD patients may experience shorter life spans, or what illnesses dominate in terminal PD, and how PD mortality compares to other illnesses of the elderly. Dementia is a known comorbidity in PD, but its pervasiveness and impact on mortality across demographic subpopulations in PD is unknown. We therefore investigated the reasons for hospitalization in the last year of life in PD, produced comparative mortality data for PD, and determined the impact of dementia on PD mortality.
Environmental exposures, most notably to pesticides, have been associated with increased risk of PD in rural areas.16;17 Lead and manganese have emerged as potential urban environmental risk factors for PD, as evidenced by recent findings of increased lead deposition in the long bones of PD cases compared to controls (OR 3.21: 95%CI 1.17–8.83)18, and our report that PD incidence in urban areas is greater where emissions of manganese are highest (RR 1.78, 95%CI 1.54–2.07), using a national, non-mobile, neurologist confirmed cohort.19 However, the potential impact post-symptom-onset exposures to pesticides or metals could have on disease course or survival is unknown. In an exploratory aim, we investigated whether PD survival varies by geography: state, region of the country, urban/ rural classification, and then examined the variation in survival by local metal emission, using our previously identified urban high/low emission areas.
Methods
This study was approved by the Human Studies Committee at Washington University School of Medicine.
Study population
Medicare is a government mandated insurance program utilized by 98% of Americans ages 65 and older. We searched all Medicare outpatient and physician claims data from the year 2002. Beneficiaries with claims for Parkinson disease, ICD-9 code”332” or “332.0”, were extracted, and incident cases were identified using previously published methods.20;21 Those who also had diagnostic claims for “Secondary Parkinsonism” (332.1) or “Other Degenerative Diseases of the Basal Ganglia” (333.0), regardless of the order of diagnoses, were excluded from further analysis.
Demographic and Clinical Data
Medicare Beneficiary Annual Summary Files (BASFs) contain individual level demographic, health service utilization, and survival data, as well as clinical data on 21 common conditions, identified using ICD-9 based algorithms.22We used the clinical data from these files to calculate an age-weighted modified Charlson comorbidity index for each PD case.23These data were also used to determine whether a PD case had been diagnosed with “Alzheimer dementia/ Senile dementia or related disorders “according to the Centers for Medicare and Medicaid services Chronic Condition Warehouse algorithm22 (hereafter referred to as “dementia”) between 1997 (the first year available) and 2008.
To investigate terminal health experiences in PD, we extracted inpatient clinical summary data and health care service utilization data from the 2005 BASF for PD cases who died between Jan 1, 2006 and March 30, 2007. Last year of life hospitalization, skilled nursing facility, and hospice utilization rates were calculated. To identify specific illnesses that factor in the demise of a person with PD, we extracted the first ten (all that were available in this datset) DRG (Diagnosis Related Group) codes for each hospitalization that occurred in the year leading to death. Over 500 standard DRG codes are used nationwide to indicate the clinical reason for each admission or diagnosis. These were grouped by organ system or disease process: cardiovascular, infection, pulmonary, malignancy, gastrointestinal, cerebrovascular, musculoskeletal, psychiatric, and other. Hospitalizations for “Degenerative Nervous System Disorders” were assigned to the category “Parkinson disease”. Finally, clinical and survival data for the entire aged Medicare population were extracted from these files to compare PD mortality to other common diseases of the elderly.
Geographical Factors
Residential information was used to assign each PD case to 1) a state/ U.S. territory, 2) a census region (Northeast, Midwest, South, West), and 3) a USDA Rural-Urban Continuum category.24;25 To investigate the impact of passive environmental metal exposure on PD survival in urban areas, we applied our previously developed county-level metal exposure classification, derived from Environmental Protection Agency Toxic Release Inventory data. A Geographical Information System (GIS) was used to spatially link geographical data to the residential, demographic and clinical data, allowing quantitative analysis of survival by state, region, and between urban areas with high or low metal release.
Descriptive Analyses
The race, sex, age and geographic distributions of the study population were determined. We compared the cumulative incidence of dementia in by race, age and sex. For investigation of terminal PD health care consumption we report last-year-of-life hospital, skilled nursing facility and hospice utilization rates for those who died in 2006 or the first quarter of 2007. We also identified the clinical condition categories associated with hospitalization in this terminal PD cohort. To provide comparative mortality data in PD patients, we compared crude mortality rates in incident PD patients to patients in the entire Medicare beneficiary population with myocardial infarction, colorectal cancer, congestive heart failure, ischemic heart disease, chronic obstructive pulmonary disease, Alzheimer dementia, hip fracture and stroke/transient ischemic attack.
Survival Analyses
Survival status was determined from 2002–2008. Cox proportional hazards models estimated the risk of death associated with demographic, clinical and geographic variables. The time to event variable was from the beginning of the study period to the date of death (measured in months). Surviving cases were censored at the end of the calendar year in 2008.
Our primary model examined the risk of death according to race (White, Black, Hispanic or Asian), age at diagnosis and sex. A second model included the diagnosis of dementia as a variable of interest. Separately, we investigated survival according to geographic variables: state, census region and rurality. We then compared survival between PD patients residing in urban counties with the lowest and highest quartiles of lead and manganese release. We adjusted all analyses for race, age, sex, and for socioeconomic, clinical and health care predictors that may influence survival in PD: socioeconomic deprivation26, age-weighted modified comorbidity index and treating physician specialty.27 Finally, we compared the associated with PD to that of common life threatening diseases of the elderly, adjusting the model for race, age, sex, and comorbidity index.
Statistical Analyses
Standard methods were used to produce Odds ratios or Cox proportion hazard coefficients with 95% confidence intervals. Statistical analyses were performed using SPSS v.16 and 17.
Results
Subject Demographics
We identified 138,728 Medicare beneficiaries with incident Parkinson Disease, 99.3% of whom were identified by ICD-9 code “332.0”. Whites comprised 90.6 percent of the cohort, the remaining were Black (6.1%), Hispanic (2.2 %) or Asian (1.1%). The age-adjusted incidence of PD in our cohort was greater in men (537.36 per 100,000) than in women (367.70 per 100,000), consistent with previous studies (Table 1).
Table 1.
Demographic characteristics of Medicare beneficiaries with incident Parkinson disease in the U.S. (year=2002).
| Patient Characteristics |
Incident PD Cases (Total = 138,728) |
|
|---|---|---|
| n | % | |
| Sex | ||
| Males | 65,423 | 47.2 |
| Females | 73,305 | 52.8 |
| Race | ||
| White | 125,660 | 90.6 |
| Black | 8,527 | 6.1 |
| Hispanic | 3,036 | 2.2 |
| Asian | 1,505 | 1.1 |
| Age * | ||
| 67–69 | 9,638 | 6.9 |
| 70–74 | 23,391 | 16.9 |
| 75–79 | 33,789 | 24.4 |
| 80–84 | 35,198 | 25.4 |
| 85+ | 37,812 | 26.5 |
| Population Density ** | ||
| Urban (population >250,000) | 106,602 | 76.8 |
| Rural (population <2,500) | 8,936 | 6.4 |
| Total Person-years of follow up | 832,368 person-years | |
To be designated as an incident case, a beneficiary was required to have two years of Medicare data with no PD claims; therefore, youngest age possible is 67.
According to the United States Department of Agriculture Rural Urban Continuum Code. Data on intermediate classes are not listed.
Dementia had been diagnosed in 69.6% of our study population by the end of the study period. Thirty one percent (n=43621) of PD cases had documented clinical evidence of dementia or cognitive impairment prior to PD diagnosis. The highest frequency of dementia was found in Blacks (78.2%), followed by Hispanics (73.1%). White and Asian PD subjects had lower, similar rates of dementia (69.0% and 66.8%, respectively). Seventy-one percent of women with incident PD were diagnosed with dementia within 6 years of diagnosis, compared to 67.5% of men. Dementia frequency increased with age (Table 2).
Table 2.
Occurrence of Dementia/Cognitive Impairment (CI) in Incident Parkinson Disease Compared to Total Medicare population
| Variable | Dementia %(n) | Adjusted Risk of Dementia** OR (95% CI) |
|---|---|---|
| Sex | ||
| Males | 67.5 (44135) | REF. |
| Females | 71.5 (52424) | 1.13 (1.11– 1.16) |
| Race | ||
| White | 69.0 (86668) | REF. |
| Black | 78.2 (6667) | 1.72(1.63–1.81) |
| Hispanic | 73.1 (2219) | 1.26 (1.16–1.37) |
| Asian | 66.8 (1005) | 0.89 (0.79–0.99) |
| Age at onset * | ||
| 67–69 | 50.2 (4788) | REF. |
| 70–74 | 59.1 (13824) | 1.41 (1.37–1.51) |
| 75–79 | 67.2 (22705) | 2.04 (1.95–2.14) |
| 80–84 | 74.4 (26174) | 2.90 (2.77–3.04) |
| 85+ | 79.0 (29068) | 3.73 (3.56–3.91) |
To be designated as an incident case, a beneficiary was required to have two years of Medicare data with no PD claims; therefore, youngest age possible is 67.
Adjusted for age, race, and sex. Dementia was determined from 1997–2008 in PD cases diagnosed in 2002.
Survival According to Patient Characteristics and Clinical Conditions
Sixty-four percent of Parkinson disease subjects died during the 6 year study period. Blacks had the highest crude death rate (66.4%), followed closely by Whites (64.6%). Hispanics had a lower frequency of death (55.4%); Asians had the lowest death rate (50.8%). Adjusting for age, sex, comorbidity index, socioeconomic deprivation and treating physician specialty with Whites as the reference group, Blacks had a slightly higher risk of death (HR=1.05, 95%CI 1.02–1.08), but Hispanics had a 14% (HR 0.86, 95%CI 0.82–0.91) and Asians had a 27% (HR 0.72, 95%CI 0.65–0.80) lower adjusted likelihood of death. Women with PD had a 26% lower adjusted risk of death than men (HR=0.74, 95%CI: 0.73–0.75). Survival decreased with age. PD with dementia had a lower survival rate (28.1%) than those without dementia (53.9%). Demented PD cases were 72% more likely to die during the six year study period (HR 1.72, 95% CI: 1.69–1.75) (Table 3).
Table 3.
PD Death According to Subject Characteristics and Disease Complications.
| Variable | Unadjusted Death Rate % (n) | Unadjusted Risk of Death HR (95%CI) | Adjusted 6 year Risk of Death* HR (95% CI) |
|---|---|---|---|
| Sex | |||
| Males | 67.1 (43871) | REF. | REF. |
| Females | 62.0 (45437) | 0.87 (0.85–0.88) | 0.74 (0.73–0.75) |
| Race | |||
| White | 64.6 (81203) | REF. | REF. |
| Black | 66.4 (5659) | 1.05 (1.02–1.08) | 1.05 (1.02–1.08) |
| Hispanic | 55.4 (1681) | 0.82 (0.77–0.86) | 0.86 (0.82–0.91) |
| Asian | 50.8 (765) | 0.68 (0.63–0.73) | 0.72 (0.65–0.80) |
| Age ** | |||
| 67–69 | 37.9 (3614) | REF. | REF. |
| 70–74 | 47.0 (10996) | 1.32 (1.27–1.37) | 1.31 (1.26–1.37) |
| 75–79 | 58.1 (19644) | 1.81 (1.75–1.87) | 1.81 (1.74–1.88) |
| 80–84 | 69.4 (24435) | 2.47 (2.39–2.56) | 2.49 (2.40–2.59) |
| 85+ | 83.2 (30619) | 3.82 (3.69–3.95) | 3.9 (3.79–4.01) |
| Disease Complications | |||
| No Dementia | 47.1 (19874) | REF. | REF. |
| Dementia | 71.9 (69434) | 1.85 (1.82–1.87) | 1.72 (1.69–1.75) |
Adjusted for race, sex, age, dementia status, socioeconomic deprivation score, physician specialty and age weighted modified Charlson comorbidity index.
To be designated as an incident case, a beneficiary was required to have two years of Medicare data with no PD claims; therefore, youngest age possible is 67.
Survival According to Geographic Variables
Crude death rates and adjusted likelihood of death were similar across states, between regions of the country, and by rural/urban classification (Table 3). However, adjusted PD death risk was 19% higher in those living in urban areas with high industrial manganese output at the time of diagnosis (HR: 1.19, 95%CI 1.10–1.29), when compared to the adjusted risk in low manganese counties. A sensitivity analysis using only neurologist diagnosed cases reduced the magnitude, but not the direction of this finding. There was no increase in risk of death associated with residence in an urban county with high industrial lead emission.
Comparative Mortality
Beneficiaries with PD have crude mortality rates comparable to Medicare beneficiaries with incident diagnoses of acute myocardial infarction (65.8%), hip fracture (66.6%) and Alzheimer dementia (68.2%). As displayed in table 4, the age, race, and sex adjusted six year risk of death among those with PD is nearly four times greater than those without PD or other common diseases (OR: 3.87, 95% CI 3.82– 3.93). Additionally, those with PD have a significantly higher adjusted mortality than those with new diagnoses of colorectal cancer, stroke/transient ischemic attack, ischemic heart disease and chronic obstructive pulmonary disease (Table 4).
Table 4.
PD Mortality Compared to Common Diseases of the Elderly (2002–2008)
| Disease | Crude Death Rate | Adjusted 6 year Risk of Death** HR (95% CI) | ||
|---|---|---|---|---|
| Percent | n | N | ||
| No Disease * | 24.4 | 7,263,150 | 29,811,565 | REF. |
| Parkinson Disease | 64.4 | 89,308 | 138,728 | 3.87 (3.82–3.83) |
| Alzheimer Dementia | 68.2 | 593,030 | 869,056 | 2.93 (2.92–2.95) |
| Stroke/Transient Ischemic Attack | 52.5 | 348,834 | 664,939 | 2.03 (2.02–2.04) |
| Acute Myocardial Infarction | 65.8 | 44,521 | 67,694 | 3.62 (3.56–3.69) |
| Ischemic Heart Disease | 32.5 | 488,580 | 1,504,725 | 1.46 (1.46–1.47) |
| Congestive Heart Failure | 50.9 | 438,717 | 861,756 | 1.93 (1.92–1.94) |
| Colorectal Cancer | 51.0 | 43,734 | 85,753 | 1.70 (1.67–1.72) |
| Chronic Obstructive Pulmonary Disease | 44.7 | 244,090 | 546,180 | 1.88 (1.87–1.89) |
| Hip Fracture | 76.2 | 106,062 | 157922 | 3.74 (3.70–3.79) |
Indicates those without the following incident diagnoses as identified by Medicare Chronic Condition algorithms: Parkinson disease, Alzheimer dementia, Alzheimer Dementia/Senile Dementia or related conditions, stroke/transient ischemic attack, acute myocardial infarction, diabetes, breast cancer, congestive heart failure, colorectal cancer, lung cancer, chronic kidney disease, chronic obstructive pulmonary disease, ischemic heart disease, hip fracture.
Adjusted for age, race, sex, and age weighted-modified Charlson comorbidity index.
Terminal PD
We identified 12,897 PD cases that died in the year 2006. Hospitalization in the last year of life was very common, 73.5% of terminal PD cases were hospitalized at least once. Hospice services were used frequently as well, by 69.8% of the dying. Skilled nursing facility services were utilized least often, by 44.0% of terminal PD cases.
We identified 44,543 hospitalizations (average 3.4 per person). DRG data was available for 44,505 of these admissions. The most common reasons for hospitalization in terminal PD were infection (20.9 %), cardiovascular disease (18.5 %), and non-infectious pulmonary disease (12.8%). Treatment of/evaluation for gastrointestinal (9.3%), genitourinary (7.4%), musculoskeletal (6.4%), nervous system (5.9%) and endocrine (4.0%) disorders were less common reasons for hospitalization. Otolaryngological, hematological, traumatic, cerebrovascular, psychiatric, and malignant diseases together accounted for the remaining 13.8% of hospitalizations. Notably, PD was the reported as one of the ten primary illness in only 1.0% of hospitalizations.
Discussion
In this nationwide, population-based study we report the survival of Medicare beneficiaries with incident Parkinson disease. Our data suggest that Parkinson disease is associated with a reduced life expectancy compared to common diseases of the elderly. Furthermore, we demonstrate that dementia occurs commonly in incident Parkinson disease occurring after age 65; this had the strongest effect on age-adjusted survival among the variables that we studied. Dying PD patients are hospitalized frequently for cardiovascular and infectious diseases rather than nervous system disorders, and access hospice care. Our exploratory data raise the question that environmental factors may also influence risk of death after diagnosis.
There are several strengths to this study. This cohort of nearly 140,000 PD patients provides substantial power to detect variables with large and small effects on survival. We are also able to provide survival data for women and minorities, who are often absent or underrepresented in PD epidemiology studies. Our study design linked otherwise separate clinical, administrative and environmental datasets to investigate unique combinations of predictors of survival in PD patients.
The use of the Medicare database for case identification also permitted detailed investigation of dementia/cognitive impairment in PD. Previous estimates of dementia in Parkinson disease are variable, suggesting a prevalence of 26% –89% in whites.28 Interestingly, the ethnic pattern of PD associated dementia in our dataset appears to follow that seen in Alzheimer disease, with blacks and women more often affected than whites and men.29 This may suggest a unique pathophysiology of dementia in blacks and women with PD or may reflect the increased susceptibility of women and blacks with PD to develop co-existent Alzheimer Dementia.30 However, given the broad definition of dementia/cognitive impairment used in this study and the difficulties with clinical diagnostic accuracy, clinicopathological studies are needed to clarify the pathologic basis of dementia in women, minorities with PD. However, our data highlight the need for prevention of or treatment for dementia in Parkinson disease, given its effect on survival.
Our methods have also allowed us to identify potential areas of improvement in the care of PD by identifying illnesses temporally associated with death. There are several reasons why PD patients may be hospitalized for cardiovascular disease and infection often prior to death. PD patients are likely susceptible to urinary tract infections and pneumonia secondary to disease-mediated bladder dysfunction and micro aspiration.31;32 Cardiovascular disease is the most common cause of hospitalization in Americans over 65,20 and PD is not thought to confer protection against cardiovascular disease risk factors. Another possible contributor, given that less than half of PD patients are treated by neurologists27, is that the management of PD symptoms consumes the majority of health care encounters. This may lead to less aggressive screening for or treatment of other, common illnesses. Additionally, non-specific symptoms such as fatigue, weakness, or exercise intolerance may be attributed by physician and patient alike to PD, when they in fact represent other illnesses, like sub-acute cardiopulmonary disease. Future studies investigating specific ways by which specialist care reduces PD mortality will be valuable.
Much research has investigated the environmental triggers of neurodegeneration in Parkinson disease, with pesticides and redox-active metals such as lead and manganese implicated in multiple studies. Exposure to a combination of maneb (an herbicide which contains manganese) and paraquat, by virtue of living within 500 meters of application sites, has been associated with an increased risk of being diagnosed with PD (HR 1.75, 95%CI: 1.13–2.73).16 We recently reported that age-, race- and sex- adjusted PD incidence is greater in urban counties with the highest industrial release of manganese (RR 1.78, 95%CI 1.54– 2.07) compared to urban counties with no or low release of this metal, using a non- mobile, neurologist-confirmed cohort.19 This additional finding of a slightly higher adjusted death risk in urban areas with high manganese output, but not just urban areas of the U.S., calls into question whether continued exposure to basal ganglia toxins after symptom onset may accelerate the clinical course of idiopathic PD, or be associated with the development of important comorbidities. Future studies with detailed clinical and exposure data are essential to determine if post symptom onset exposures to neurotoxins (including pesticides and metals) are associated with the development of more severe PD clinical features or more rapid progression.
There are several limitations to this study. Differential misdiagnosis is always a potential bias in studies that rely on clinical or administrative data. It is possible that Parkinson plus syndromes cases, which are more lethal, were included in our cohort. Future studies testing the endurance and robustness of our case definition methods may include prescription data record review (in cases diagnosed after 2007 when the Medicare Prescription Drug Act (ref) was passed) may be helpful. However, these diseases are rare and are unlikely to significantly alter our primary findings. It is possible that dementia in men and whites with PD may be underreported, but a recent study suggests that white males tend to see neurologists more often than PD patients in other demographic groups.27 Differences in health care seeking behaviors or health care access could potentially impact our baseline population, clinical, or survival data. Although we accounted for known demographic, comorbid and physician factors likely to impact survival, there may be undiscovered confounders that would alter the risk ratios we obtained.
Our environmental data analyses were performed primarily to generate hypotheses for future environmental epidemiology research, assess for geographical confounders in survival, and should be interpreted cautiously. We lack historical individual exposure data (community or occupational) which are impossible to obtain retrospectively for an administratively identified cohort over the decades of exposure that may be relevant for an adult onset neurodegenerative disease. The change in risk, although specific to manganese, was modest, and could be explained entirely by unknown confounders. There may be unknown non-neurological mechanisms by which PD mortality is increased in urban areas with high metal emissions. In spite of these limitations, post symptom onset environmental exposures may need to be considered when investigating future neuroprotective therapies in PD as ongoing individual exposures may influence disease course.
Table 5.
PD Mortality According to Geographical Variables (2002–2008)
| Variable | Unadjusted Death Rate % (n) | Unadjusted risk of Death HR (95%CI) | Adjusted 6 Year Risk of Death* HR (95%CI) |
|---|---|---|---|
| Geographical Region ** | |||
| Northeast | 65.1 (20088) | REF. | REF. |
| Midwest | 65.1 (22597) | 0.99 (0.98–1.01) | 1.04 (1.03–1.07) |
| South | 65.5 (33253) | 1.00 (0.99–1.02) | 1.06 (1.05–1.08) |
| West | 60.5 (12316) | 0.89 (0.88–0.92) | 0.93 (0.91–0.95) |
| Population Density † | |||
| Completely Urban (>1,000,000) | 64.7 (68972) | REF. | REF. |
| Completely Rural (<2,500) | 62.4 (5578) | 0.89 (0.84–0.95) | 0.91 (0.88–0.94) |
| Urban Heavy Metal Release ‡ | |||
| Low Manganese (<25th%tile) | 61.9 (3011) | REF. | REF. |
| High Manganese (>75th%tile) | 66.2 (5982) | 1.06 (1.03–1.08) | 1.19 (1.10–1.29) |
| Low Lead (<25th%tile) | 62.9 (1663) | REF. | REF. |
| High Lead (>75th%tile) | 64.4 (13117) | 1.01 (0.96–1.08) | 1.03 (0.98–1.09) |
Adjusted for race, age, sex, physician specialty, socioeconomic deprivation and age-weighted modified Charlson comorbidity index.
According to the United States Department of Interior/Census Geographical Division System.
According to the USDA Rural Urban Continuum Code Classification.
Total Onsite release as reported to the Environmental Protection Agency.
Acknowledgement
This work was supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (5T32NS007205-27); the National Center for Research Resources and National Institutes of Health Roadmap for Medical Research (UL1RR024992, KL2RR024994); National Institute for Environmental Health Sciences at the National Institutes of Health (K24ES017765); the St. Louis Chapter of the American Parkinson Disease Association; the American Parkinson Disease Association, Walter and Connie Donius; and the Robert Renschen Fund.
Footnotes
Author Contributions Dr. Allison Willis performed primary data analysis, primary authorship of the manuscript. Dr. Willis had full access to and takes full responsibility for the accuracy of the data.
Dr. Bradley Evanoff: provided input for study design, manuscript revision.
Dr. Nathan Kung assisted with data analysis, manuscript review.
Dr. Mario Schootman: provided study design input, manuscript review.
Dr. Joel Perlmutter: provided study design input, manuscript review.
Dr. Brad Racette: provided study design input, manuscript review.
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