Loss of Ovarian Hormones and Accelerated Somatic and Mental Aging.

Bilateral oophorectomy in premenopausal women is a unique condition causing the abrupt and premature loss of ovarian hormones, primarily estrogen. Bilateral oophorectomy causes an alteration of several fundamental aging processes at the cellular, tissue, organ, and system levels, leading to multimorbidity, frailty, and reduced survival. However, many questions remain unanswered.

Parkinson disease with and without Dementia: A prevalence study and future projections.

BACKGROUND: Limited population-based information is available on the co-occurrence of dementia and PD. However, projecting the prevalence of PD with and without dementia during the next 50 years is crucial for planning public-health and patient-care initiatives. OBJECTIVES: The objective of this study was to project the prevalence of PD with and without dementia in the United States by 2060. METHODS: We used the Rochester Epidemiology Project medical records-linkage system to identify all persons with PD with or without dementia residing in Olmsted County, Minnesota, on January 1, 2006. A movement disorders specialist reviewed the complete medical records of each person to confirm the presence of PD. We calculated the age- and sex-specific prevalence of PD with and without dementia and projected U.S. prevalence through 2060. RESULTS: We identified 296 persons with PD with and without dementia on the prevalence date (187 men, 109 women); the overall prevalence increased with age from 0.01% (30-39 years) to 2.83% (≥90 years). The prevalence of PD without dementia increased with age from 0.01% (30-39 years) to 1.25% (≥90 years). The prevalence of PD with dementia increased with age from 0.10% (60-69 years) to 1.59% (≥90 years). The prevalence was higher in men than in women for all subtypes and all age groups. We project by 2060 an approximate doubling of the number of persons with PD without dementia and a tripling of the number of persons with PD with dementia in the United States. CONCLUSIONS: The prevalence of PD with and without dementia increases with age and is higher in men than women. We project that the number of persons with PD in the United States will increase substantially by 2060. © 2018 International Parkinson and Movement Disorder Society.

Prevalence of and indications for antipsychotic use in Parkinson's disease.

BACKGROUND: The prevalence of patients with PD taking antipsychotics is unknown. OBJECTIVE: To measure the prevalence of patients with PD taking antipsychotics. METHODS: We used the medical records-linkage system of the Rochester Epidemiology Project to study the use of antipsychotic medication in all persons with Parkinson disease in Olmsted County, Minnesota on 1 January 2006. RESULTS: There were 296 patients with PD in Olmsted County on 1 January 2006. The overall prevalence of antipsychotic use was 9.8% (29 of 296); 95.5% (28 of 29) of the patients had dementia when initiating antipsychotics. The most frequent indication (71.4%; 20 of 28) was psychosis or behavior threatening to the patient or others. CONCLUSIONS: The prevalence of antipsychotic use in patients with PD is lower than expected from previously reported cumulative incidences. Dementia is highly prevalent in those starting antipsychotics. Most of the patients on antipsychotics had a reasonable risk-benefit ratio for taking them. © 2017 International Parkinson and Movement Disorder Society.

Rochester Epidemiology Project Data Exploration Portal.

INTRODUCTION: The goal of this project was to develop an interactive, web-based tool to explore patterns of prevalence and co-occurrence of diseases using data from the expanded Rochester Epidemiology Project (E-REP) medical records-linkage system. METHODS: We designed the REP Data Exploration Portal (REP DEP) to include summary information for people who lived in a 27-county region of southern Minnesota and western Wisconsin on January 1, 2014 (n = 694,506; 61% of the entire population). We obtained diagnostic codes of the International Classification of Diseases, 9th edition, from the medical records-linkage system in 2009 through 2013 (5 years) and grouped them into 717 disease categories. For each condition or combination of 2 conditions (dyad), we calculated prevalence by dividing the number of persons with a specified condition (numerator) by the total number of persons in the population (denominator). We calculated observed-to-expected ratios (OERs) to test whether 2 conditions co-occur more frequently than would co-occur as a result of chance alone. RESULTS: We launched the first version of the REP DEP in May 2017. The REP DEP can be accessed at http://rochesterproject.org/portal/. Users can select 2 conditions of interest, and the REP DEP displays the overall prevalence, age-specific prevalence, and sex-specific prevalence for each condition and dyad. Also displayed are OERs overall and by age and sex and maps of county-specific prevalence of each condition and OER. CONCLUSION: The REP DEP draws upon a medical records-linkage system to provide an innovative, rapid, interactive, free-of-charge method to examine the prevalence and co-occurrence of 717 diseases and conditions in a geographically defined population.

Incidence and time trends of drug-induced parkinsonism: A 30-year population-based study.

BACKGROUND: Epidemiological studies of drug-induced parkinsonism remain limited. OBJECTIVES: To investigate the incidence and time trends of drug-induced parkinsonism over 30 years in a geographically defined American population. METHODS: We used the medical records-linkage system of the Rochester Epidemiology Project to identify all persons in Olmsted County, Minnesota, who received a screening diagnostic code for parkinsonism from 1976 through 2005. A movement disorders specialist reviewed the complete medical records of each person to confirm the presence of drug-induced parkinsonism associated with dopamine-blocking or dopamine-depleting medications. RESULTS: Among 906 incident cases of parkinsonism from 1976 to 2005, 108 persons had drug-induced parkinsonism (11.9%). The average annual incidence rate of drug-induced parkinsonism was 3.3 per 100,000 person-years, was higher in women, and increased with older age. Drug-induced parkinsonism was the fifth-most common type of parkinsonism overall; however, it was the most common type among persons younger than age 40 years. Typical antipsychotic drugs were the most common class of drugs associated with parkinsonism, whereas atypical antipsychotic drugs were rarely involved. The incidence rate of drug-induced parkinsonism decreased 32.0% per decade (relative risk = 0.68; 95% confidence interval: 0.49-0.94) and 68.6% over the 30 years of the study. The decrease was similar in men (65.2%) and women (69.4%); however, the trend was significant only in women. CONCLUSIONS: The incidence of drug-induced parkinsonism increased with older age and was higher in women at all ages. Typical antipsychotic drugs were the most common cause. The incidence of drug-induced parkinsonism decreased over the 30 years of the study because of changes in drug use. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Does where you live influence how your vestibular schwannoma is managed? Examining geographical differences in vestibular schwannoma treatment across the United States.

The management of small- to medium-sized vestibular schwannoma (VS) remains controversial. Despite a lack of compelling evidence supporting one treatment modality over others, many providers and institutions remain highly biased toward one particular therapy-microsurgery, radiation, or primary observation. The objective of the current study was to estimate the impact of geography on disease presentation and initial treatment of VS in the United States. An analysis of the Surveillance, Epidemiology, and End Results (SEER) database identified 9761 patients with VS that were managed across the 16 SEER geographic registry areas. Univariate analyses demonstrated strong associations between geographic location and tumor size at diagnosis (P < 0.0001). When analyzing the 6115 subjects with tumors between 0 and 3 cm in size, multivariable models identified strong associations between place of residence and treatment modality (P < 0.0001). These multivariable models demonstrated that in many cases the impact of place of residence on treatment selection was greater than other established variables such as tumor size and age. To our knowledge, this is the first study to evaluate geographic trends in VS patient demographics, tumor size and management in the United States. These data suggest that disease presentation and treatment modality are significantly influenced by regional referral patterns, provider or institutional treatment preferences, and regional availability of subspecialty expertise. Understanding geographic bias is important for patients, referring physicians, and treatment providers alike. Until there is clear evidence supporting one therapy over others, multidisciplinary consultation with a minimum of a neurotologist, neurosurgeon, and radiation oncologist or radiosurgeon should be offered in order to provide balanced counseling and accurate informed consent.

Vestibular schwannoma and pituitary adenoma in the same patient: coincidence or novel clinical association?

Over the years the authors have evaluated a number of patients with vestibular schwannomas (VS) who have also been diagnosed with a pituitary adenoma (PA). No associations between these tumors have been established to date. The objective of the current study is to investigate the epidemiological association between VS and PA via a population-based study and to supplement these data with a retrospective case series of 12 patients who were evaluated at the authors' center over the past 15 years. An analysis of the Surveillance, Epidemiology, and End Results database including all patients identified with a diagnosis of VS and/or PA was performed. A comparison between the observed and expected annual incidence was calculated and population differences between those with VS + PA were compared with single tumor populations. 9888 patients with VS and 26,577 patients with PA were identified among 822.9 million person-years. Within these populations, 31 patients were diagnosed with both tumor types. Overall, 1 in every 319 patients with VS was also diagnosed with a PA. The average annual incidence for VS was 1.2 per 100,000 persons per year while the average PA rate was 3.2 per 100,000 persons per year. The observed rate of co-incident VS and PA was greater than what is expected by chance alone assuming independence. The cohort of patients with coexisting VS and PA were older and more commonly male compared to VS-only or PA-only groups. These data strongly suggest that a common environmental or genetic predisposition exists for VS and PA development. Further study of this population may help elucidate the cause of tumorigenesis in a subset of patients with seemingly sporadic tumors.

Persistent changes in calcium-regulating hormones and bone turnover markers in living kidney donors more than 20 years after donation.

In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3 months and 36 months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared with matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium- and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89 pg/mL vs. controls 38.79 pg/mL, percent difference = -12.6%; P < .001), increases in both parathyroid hormone (when corrected for ionized calcium; donors mean 52.98 pg/mL vs. controls 46.89 pg/mL,% difference 13%; P = .03) and ionized calcium levels (donors mean 5.13 mg/dL vs. controls 5.04 mg/dL; P < .001), and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency toward thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.

Fracture Risk Among Living Kidney Donors 25 Years After Donation.

Importance: Living kidney donors may have an increased risk of fractures due to reductions in kidney mass, lower concentrations of serum 1,25-dihydroxyvitamin D, and secondary increases in serum parathyroid hormone. Objective: To compare the overall and site-specific risk of fractures among living kidney donors with strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so. Design, Setting, and Participants: This survey study was conducted between December 1, 2021, and July 31, 2023. A total of 5065 living kidney donors from 3 large transplant centers in Minnesota were invited to complete a survey about their bone health and history of fractures, and 16 156 population-based nondonor controls without a history of comorbidities that would have precluded kidney donation were identified from the Rochester Epidemiology Project and completed the same survey. A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Statistical analyses were performed from May to August 2023. Exposure: Living kidney donation. Main Outcomes and Measures: The rates of overall and site-specific fractures were compared between living kidney donors and controls using standardized incidence ratios (SIRs). Results: At the time of survey, the 2132 living kidney donors had a mean (SD) age of 67.1 (8.9) years and included 1245 women (58.4%), and the 2014 controls had a mean (SD) age of 68.6 (7.9) years and included 1140 women (56.6%). The mean (SD) time between donation or index date and survey date was 24.2 (10.4) years for donors and 27.6 (10.7) years for controls. The overall rate of fractures among living kidney donors was significantly lower than among controls (SIR, 0.89; 95% CI, 0.81-0.97). However, there were significantly more vertebral fractures among living kidney donors than among controls (SIR, 1.42; 95% CI, 1.05-1.83). Conclusions and Relevance: This survey study found a reduced rate of overall fractures but an excess of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D3 may reduce the numbers of vertebral fractures and patient morbidity.

Older Tissue Age Derived From Abdominal Computed Tomography Biomarkers of Muscle, Fat, and Bone Is Associated With Chronic Conditions and Higher Mortality.

OBJECTIVE: To determine whether body composition derived from medical imaging may be useful for assessing biologic age at the tissue level because people of the same chronologic age may vary with respect to their biologic age. METHODS: We identified an age- and sex-stratified cohort of 4900 persons with an abdominal computed tomography scan from January 1, 2010, to December 31, 2020, who were 20 to 89 years old and representative of the general population in Southeast Minnesota and West Central Wisconsin. We constructed a model for estimating tissue age that included 6 body composition biomarkers calculated from abdominal computed tomography using a previously validated deep learning model. RESULTS: Older tissue age associated with intermediate subcutaneous fat area, higher visceral fat area, lower muscle area, lower muscle density, higher bone area, and lower bone density. A tissue age older than chronologic age was associated with chronic conditions that result in reduced physical fitness (including chronic obstructive pulmonary disease, arthritis, cardiovascular disease, and behavioral disorders). Furthermore, a tissue age older than chronologic age was associated with an increased risk of death (hazard ratio, 1.56; 95% CI, 1.33 to 1.84) that was independent of demographic characteristics, county of residency, education, body mass index, and baseline chronic conditions. CONCLUSION: Imaging-based body composition measures may be useful in understanding the biologic processes underlying accelerated aging.

Abdominal Body Composition Reference Ranges and Association With Chronic Conditions in an Age- and Sex-Stratified Representative Sample of a Geographically Defined American Population.

BACKGROUND: Body composition can be accurately quantified from abdominal computed tomography (CT) exams and is a predictor for the development of aging-related conditions and for mortality. However, reference ranges for CT-derived body composition measures of obesity, sarcopenia, and bone loss have yet to be defined in the general population. METHODS: We identified a population-representative sample of 4 900 persons aged 20 to 89 years who underwent an abdominal CT exam from 2010 to 2020. The sample was constructed using propensity score matching an age and sex stratified sample of persons residing in the 27-county region of Southern Minnesota and Western Wisconsin. The matching included race, ethnicity, education level, region of residence, and the presence of 20 chronic conditions. We used a validated deep learning based algorithm to calculate subcutaneous adipose tissue area, visceral adipose tissue area, skeletal muscle area, skeletal muscle density, vertebral bone area, and vertebral bone density from a CT abdominal section. RESULTS: We report CT-based body composition reference ranges on 4 649 persons representative of our geographic region. Older age was associated with a decrease in skeletal muscle area and density, and an increase in visceral adiposity. All chronic conditions were associated with a statistically significant difference in at least one body composition biomarker. The presence of a chronic condition was generally associated with greater subcutaneous and visceral adiposity, and lower muscle density and vertebrae bone density. CONCLUSIONS: We report reference ranges for CT-based body composition biomarkers in a population-representative cohort of 4 649 persons by age, sex, body mass index, and chronic conditions.

Risk factors for Parkinson's disease may differ in men and women: an exploratory study.

Although several environmental and genetic risk or protective factors have been associated with Parkinson's disease (PD), their interactions overall and in men and women separately remain unknown. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. We considered the following 12 risk or protective factors: personal history of head trauma, pesticide use, immunologic diseases, anemia, hysterectomy (in women only), cigarette smoking, coffee consumption, and education; and family history of parkinsonism, essential tremor, dementia, or psychiatric disorders. We used recursive partitioning analyses to explore interactions overall and in men and women separately and used logistic regression analyses to test for interactions. In the overall group, we observed the independent effects of anemia, lack of coffee consumption (never vs. ever), and head trauma; however, the findings were different in men and women. In men, we observed the independent effects of lack of coffee consumption (never vs. ever), head trauma, and pesticide use, and a suggestive synergistic interaction between immunologic diseases and family history of dementia. By contrast, in women, anemia was the most important factor and we observed a suggestive synergistic interaction between anemia and higher education. Risk factors for PD and their interactions may differ in men and women.

Completion of the human papillomavirus vaccination series lags in Somali adolescents.

OBJECTIVE: It is unknown whether the Somali population in the United States is likely to participate in human papillomavirus (HPV) vaccination. We aimed to determine whether Somali girls living in a US community are following the recommendations for HPV vaccination. MATERIALS AND METHODS: We conducted a study of HPV vaccination among Somali girls seen at Mayo Clinic, Rochester, MN. Each Somali subject was matched by year of birth to white/non-Hispanic subjects in a 1:3 ratio. We abstracted information between August 1, 2006, and December 31, 2009, related to HPV vaccine series initiation and completion. Initiation and completion frequencies were compared between study groups using the χ(2) test. RESULTS: A total of 251 Somali and 727 white/non-Hispanic girls were identified, using the Rochester Epidemiology Project, who met all inclusion criteria for final analysis. A total of 114 Somali girls (45%) and 334 white/non-Hispanic girls (46%) initiated the series (odds ratio = 0.98; 95% confidence interval = 0.73-1.31), but only 59 Somali girls (52%) completed the vaccination series, compared with 240 (72%) of the white/non-Hispanic girls (odds ratio = 0.42; 95% confidence interval = 0.27-0.65). CONCLUSIONS: We found Somali girls to be generally accepting of initiating the HPV vaccine series but less likely to complete the series as compared with white non-Hispanic girls of the same age.

Integrating Environmental Data with Medical Data in a Records-Linkage System to Explore Groundwater Nitrogen Levels and Child Health Outcomes.

Background: The Rochester Epidemiology Project (REP) medical records-linkage system offers a unique opportunity to integrate medical and residency data with existing environmental data, to estimate individual-level exposures. Our primary aim was to provide an archetype of this integration. Our secondary aim was to explore the association between groundwater inorganic nitrogen concentration and adverse child and adolescent health outcomes. Methods: We conducted a nested case-control study in children, aged seven to eighteen, from six counties of southeastern Minnesota. Groundwater inorganic nitrogen concentration data were interpolated, to estimate exposure across our study region. Residency data were then overlaid, to estimate individual-level exposure for our entire study population (n = 29,270). Clinical classification software sets of diagnostic codes were used to determine the presence of 21 clinical conditions. Regression models were adjusted for age, sex, race, and rurality. Results: The analyses support further investigation of associations between nitrogen concentration and chronic obstructive pulmonary disease and bronchiectasis (OR: 2.38, CI: 1.64-3.46) among boys and girls, thyroid disorders (OR: 1.44, CI: 1.05-1.99) and suicide and intentional self-inflicted injury (OR: 1.37, CI: >1.00-1.87) among girls, and attention deficit conduct and disruptive behavior disorders (OR: 1.34, CI: 1.24-1.46) among boys. Conclusions: Investigators with environmental health research questions should leverage the well-enumerated population and residency data in the REP.

Synergistic interactions of obesity with sex, education, and smoking and accumulation of multi-morbidity (MM) across the lifespan.

Objectives: Obesity is a potentially modifiable risk factor that has been consistently associated with the development and progression of multi-morbidity (MM). However, obesity may be more problematic for some persons compared to others because of interactions with other risk factors. Therefore, we studied the effect of interactions between patient characteristics and overweight and obesity on the rate of accumulation of MM. Methods: We studied 4 cohorts of persons ages 20-, 40-, 60-, and 80-years residing in Olmsted County, Minnesota between 2005 and 2014 using the Rochester Epidemiology Project (REP) medical records-linkage system. Body mass index, sex, race, ethnicity, education, and smoking status were extracted from REP indices. The rate of accumulation of MM was calculated as the number of new chronic conditions accumulated per 10 person years through 2017. Poisson rate regression models were used to identify associations between characteristics and rate of MM accumulation. Additive interactions were summarized using relative excess risk due to interaction, attributable proportion of disease, and the synergy index. Results: Greater than additive synergistic associations were observed between female sex and obesity in the 20- and 40-year cohorts, between low education and obesity in the 20-year cohort (both sexes), and between smoking and obesity in the 40-year cohort (both sexes). Conclusions: Interventions targeted at women, persons with lower education, and smokers who also have obesity may result in the greatest reduction in the rate of MM accumulation. However, interventions may need to focus on persons prior to mid-life to have the greatest effect.

Convergence of four measures of multi-morbidity.

Objectives: To compare the agreement between percentile ranks from 4 multi-morbidity scores. Design: Population-based descriptive study. Setting: Olmsted County, Minnesota (USA). Participants: We used the medical records-linkage system of the Rochester Epidemiology Project (REP; http://www.rochesterproject.org) to identify all residents of Olmsted County, Minnesota who reached one or more birthdays between 1 January 2005 and 31 December 2014 (10 years). Methods: For each person, we calculated 4 multi-morbidity scores using readily available diagnostic code lists from the US Department of Health and Human Services, the Clinical Classifications Software, and the Elixhauser Comorbidity Index. We calculated scores using diagnostic codes received in the 5 years before the index birthday and fit quantile regression models across age and separately by sex to transform unweighted, simple counts of conditions into percentile ranks as compared to peers of same age and of same sex. We compared the percentile ranks of the 4 multi-morbidity scores using intra-class correlation coefficients (ICCs). Results: We assessed agreement in 181,553 persons who reached a total of 1,075,433 birthdays at ages 18 years through 85 years during the study period. In general, the percentile ranks of the 4 multi-morbidity scores exhibited high levels of agreement in 6 score-to-score pairwise comparisons. The agreement increased with older age for all pairwise comparisons, and ICCs were consistently greater than 0.65 at ages 50 years and older. Conclusions: The assignment of percentile ranks may be a simple and intuitive way to assess the underlying trait of multi-morbidity across studies that use different measures.

Metabolic markers or conditions preceding Parkinson's disease: a case-control study.

Several metabolic markers or conditions have been explored as possible risk or protective factors for Parkinson's disease (PD); however, results remain conflicting. We further investigated these associations using a case-control study design. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to abstract information about body mass index (BMI), cholesterol level, hypertension, and diabetes mellitus preceding the onset of PD (or the index year). There were no significant differences between cases and controls for the metabolic markers or conditions investigated. No significant associations were found using 2 cutoffs for BMI level (BMI ≥ 25 or BMI ≥ 30 kg/m(2) ) and 3 cutoffs for cholesterol levels (>200, >250, or >300 mg/dL). Neither a diagnosis of hypertension or the documented use of antihypertensive medications was significantly associated with the subsequent risk of PD (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.65-1.54; P = .99) nor was a diagnosis of diabetes mellitus or the use of glucose-lowering medications (OR, 0.77; 95% CI, 0.37-1.57; P = .47). Our study, based on historical information from a records-linkage system, does not support an association between BMI, cholesterol level, hypertension, or diabetes mellitus with later development of PD.

Epilepsy-related mortality is low in children: a 30-year population-based study in Olmsted County, MN.

PURPOSE: Epilepsy is a common childhood neurologic disorder, affecting 0.5-1% of children. Increased mortality occurs due to progression of underlying disease, seizure-related accidents, suicide, status epilepticus, aspiration during seizures, and sudden unexplained death in epilepsy (SUDEP). Previous studies show mortality rates of 2.7-6.9 per 1,000 person-years. Potential risk factors include poor seizure control, intractable epilepsy, status epilepticus, tonic-clonic seizures, mental retardation, and remote symptomatic cause of epilepsy. Few population-based studies of mortality and SUDEP in childhood-onset epilepsy have been published. The purpose of this study is to report mortality and SUDEP from a 30-year population-based cohort of children with epilepsy. METHODS: The Medical Diagnostic Index of the Rochester Epidemiology Project was searched for all codes related to seizure and convulsion in children living in Olmsted County, Minnesota and of ages birth through 17 years from 1980 through 2009. The medical records of these children were reviewed to identify all those with new-onset epilepsy, and to abstract other baseline and follow-up information. Potential risk factors including seizure type, epilepsy syndrome, history of status epilepticus, the presence and severity of neurologic impairment, and epilepsy outcome was reviewed. Epilepsy outcome was characterized by seizure frequency, number of antiseizure medications (antiepileptic drugs, AEDs) used, and number of AEDs failed due to lack of efficacy, and epilepsy intractability at 1 year and 2, 3, 5, 10, 15, and 20 years after epilepsy onset. We followed all children through their most recent visit to determine vital status, cause of death, and whether autopsy was performed. KEY FINDINGS: From 1980 to 2009, there were 467 children age birth through 17 years diagnosed with epilepsy while residents of Olmsted County, Minnesota, and who had follow-up beyond the time of epilepsy diagnosis. Children were followed for a median of 7.87 years after the time of diagnosis (range 0.04-29.49 years) for a total of 4558.5 person-years. Sixteen (3.4%) of the children died, or 3.51 deaths per 1,000 person-years. Two deaths were epilepsy related (12.5%) for a rate of 0.44 per 1,000 person-years. One of these children died of probable SUDEP and one died of aspiration during a seizure. The remaining 14 deaths (87.5%) were caused by other complications of underlying disease. Several risk factors for mortality were found, including abnormal cognition, abnormal neurologic examination, structural/metabolic etiology for epilepsy, and poorly controlled epilepsy. SIGNIFICANCE: Although mortality in children with epilepsy was higher than what would be expected in the general pediatric population, death occurred significantly more in children with neurologic impairment and poorly controlled epilepsy. Epilepsy-related death, including SUDEP, was rare and mortality due to epilepsy alone was similar to the expected mortality in the general population (observed deaths = 2, expected deaths = 1.77; standardized mortality ratio 1.13, 95% confidence interval 0.19-3.73, p = 0.86). By contrast, most children died of complications of the underlying neurologic disease or unrelated disease rather than the epilepsy.

Hysterectomy, oophorectomy, estrogen, and the risk of dementia.

BACKGROUND: The long-term cognitive effects of hysterectomy and oophorectomy remain controversial. OBJECTIVE: To explore the association of hysterectomy and oophorectomy with the subsequent risk of cognitive impairment or dementia. METHODS: We combined the results from two cohort studies graphically and conducted additional analyses. RESULTS: Combined results from the Mayo Clinic Cohort Study of Oophorectomy and Aging and from a Danish nationwide cohort study suggest that the extent of gynecologic surgery may correlate with a stepwise increase in the risk of cognitive impairment or dementia. Compared with women with no gynecologic surgeries, the risk of cognitive impairment or dementia was increased in women who had hysterectomy alone, further increased in women who had hysterectomy with unilateral oophorectomy, and further increased in women who had hysterectomy with bilateral oophorectomy. The risk increased with younger age at the time of the surgery. CONCLUSION: We hypothesize that both hysterectomy and oophorectomy may have harmful brain effects via direct endocrinological mechanisms or other more complex mechanisms. Estrogen deficiency appears to play a key role in these associations, and estrogen therapy may partly offset the negative effects of the surgeries.