Publications by authors named "Walter A Rocca"

197 Publications

Factors Associated With Severe COVID-19 Infection Among Persons of Different Ages Living in a Defined Midwestern US Population.

Mayo Clin Proc 2021 Jul 5. Epub 2021 Jul 5.

Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.

Objective: To identify risk factors associated with severe COVID-19 infection in a defined Midwestern US population overall and within different age groups.

Patients And Methods: We used the Rochester Epidemiology Project research infrastructure to identify persons residing in a defined 27-county Midwestern region who had positive results on polymerase chain reaction tests for COVID-19 between March 1, 2020, and September 30, 2020 (N=9928). Age, sex, race, ethnicity, body mass index, smoking status, and 44 chronic disease categories were considered as possible risk factors for severe infection. Severe infection was defined as hospitalization or death caused by COVID-19. Associations between risk factors and severe infection were estimated using Cox proportional hazard models overall and within 3 age groups (0 to 44, 45 to 64, and 65+ years).

Results: Overall, 474 (4.8%) persons developed severe COVID-19 infection. Older age, male sex, non-White race, Hispanic ethnicity, obesity, and a higher number of chronic conditions were associated with increased risk of severe infection. After adjustment, 36 chronic disease categories were significantly associated with severe infection. The risk of severe infection varied significantly across age groups. In particular, persons 0 to 44 years of age with cancer, chronic neurologic disorders, hematologic disorders, ischemic heart disease, and other endocrine disorders had a greater than 3-fold increased risk of severe infection compared with persons of the same age without those conditions. Associations were attenuated in older age groups.

Conclusion: Older persons are more likely to experience severe infections; however, severe cases occur in younger persons as well. Our data provide insight regarding younger persons at especially high risk of severe COVID-19 infection.
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http://dx.doi.org/10.1016/j.mayocp.2021.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255113PMC
July 2021

Cardiometabolic Outcomes and Mortality in Patients with Adrenal Adenomas: A Population-Based Cohort Study.

J Clin Endocrinol Metab 2021 Jun 29. Epub 2021 Jun 29.

Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.

Context: While adrenal adenomas have been linked with cardiovascular morbidity in convenience samples of patients from specialized referral centers, large-scale population-based data is lacking.

Objective: To determine the prevalence and incidence of cardiometabolic disease and assess mortality in a population-based cohort of patients with adrenal adenomas.

Design: Population-based cohort study.

Setting: Olmsted County, Minnesota.

Patients: Patients diagnosed with adrenal adenomas without overt hormone excess and age- and sex-matched referent subjects without adrenal adenomas.

Main Outcome Measure: Prevalence, incidence of cardiometabolic outcomes, mortality.

Results: Adrenal adenomas were diagnosed in 1,004 patients (58% women, median age 63 years). At baseline, patients with adrenal adenomas were more likely to have hypertension (aOR 1.96, 95% CI 1.58-2.44), dysglycemia (aOR 1.63, 95% CI 1.33-2.00), peripheral vascular disease (aOR 1.59, 95% CI 1.32-2.06), heart failure (aOR 1.64, 95% CI 1.15-2.33), and myocardial infarction (aOR 1.50, 95% CI 1.02-2.22) compared to referent subjects. During median follow-up of 6.8 years, patients with adrenal adenomas were more likely than referent subjects to develop de novo chronic kidney disease(aHR 1.46, 95% CI 1.14-1.86), cardiac arrhythmia(aHR 1.31, 95% CI 1.08-1.58), peripheral vascular disease (aHR 1.28, 95% CI 1.05-1.55), cardiovascular events (aHR 1.33, 95% CI 1.01-1.73), and venous thromboembolic events (aHR 2.15, 95% CI 1.48-3.13). Adjusted mortality was similar between the two groups.

Conclusion: Adrenal adenomas are associated with an increased prevalence and incidence of adverse cardiometabolic outcomes in a population-based cohort.
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http://dx.doi.org/10.1210/clinem/dgab468DOI Listing
June 2021

Longitudinal cohorts for harnessing the electronic health record for disease prediction in a US population.

BMJ Open 2021 06 8;11(6):e044353. Epub 2021 Jun 8.

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA

Purpose: The depth and breadth of clinical data within electronic health record (EHR) systems paired with innovative machine learning methods can be leveraged to identify novel risk factors for complex diseases. However, analysing the EHR is challenging due to complexity and quality of the data. Therefore, we developed large electronic population-based cohorts with comprehensive harmonised and processed EHR data.

Participants: All individuals 30 years of age or older who resided in Olmsted County, Minnesota on 1 January 2006 were identified for the discovery cohort. Algorithms to define a variety of patient characteristics were developed and validated, thus building a comprehensive risk profile for each patient. Patients are followed for incident diseases and ageing-related outcomes. Using the same methods, an independent validation cohort was assembled by identifying all individuals 30 years of age or older who resided in the largely rural 26-county area of southern Minnesota and western Wisconsin on 1 January 2013.

Findings To Date: For the discovery cohort, 76 255 individuals (median age 49; 53% women) were identified from which a total of 9 644 221 laboratory results; 9 513 840 diagnosis codes; 10 924 291 procedure codes; 1 277 231 outpatient drug prescriptions; 966 136 heart rate measurements and 1 159 836 blood pressure (BP) measurements were retrieved during the baseline time period. The most prevalent conditions in this cohort were hyperlipidaemia, hypertension and arthritis. For the validation cohort, 333 460 individuals (median age 54; 52% women) were identified and to date, a total of 19 926 750 diagnosis codes, 10 527 444 heart rate measurements and 7 356 344 BP measurements were retrieved during baseline.

Future Plans: Using advanced machine learning approaches, these electronic cohorts will be used to identify novel sex-specific risk factors for complex diseases. These approaches will allow us to address several challenges with the use of EHR.
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http://dx.doi.org/10.1136/bmjopen-2020-044353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190051PMC
June 2021

Risk of de novo severe carpal tunnel syndrome after bilateral oophorectomy: a population-based cohort study.

Menopause 2021 May 24;28(9):1026-1036. Epub 2021 May 24.

Women's Health Research Center, Mayo Clinic, Rochester, MN.

Objective: The incidence of carpal tunnel syndrome (CTS) is higher in women, and peaks around the age of menopause. Therefore, we investigated whether bilateral oophorectomy is associated with an increased risk of severe CTS.

Methods: We included all of the 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication between 1988 and 2007, and a random sample of 1,653 age-matched referent women who did not undergo bilateral oophorectomy in Olmsted County, MN. Diagnoses of CTS assigned to women over their entire lifetime were identified in these two cohorts. The risk of de novo severe CTS after bilateral oophorectomy (or index date) was evaluated using Cox proportional hazards models adjusted for potential confounders.

Results: Bilateral oophorectomy was associated with an increased risk of severe CTS (adjusted hazard ratio 1.65, 95% confidence interval 1.20-2.25). The risk was suggestively greater in women with lower body mass index, nulliparity, and with a benign ovarian indication for oophorectomy (nonsignificant interactions). We did not observe a protective effect of estrogen therapy after the oophorectomy. The findings were similar in secondary analyses considering the incidence of CTS of any severity or idiopathic CTS.

Conclusions: The risk of severe CTS, common in perimenopausal women, is increased after bilateral oophorectomy. The association may be causal or due to confounding. Therefore, the precise biological mechanisms explaining the association and the absence of a mitigating effect of estrogen therapy should be further investigated.
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http://dx.doi.org/10.1097/GME.0000000000001804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403136PMC
May 2021

Implementing the US Department of Health and Human Services definition of multimorbidity: a comparison between billing codes and medical record review in a population-based sample of persons 4084 years old.

BMJ Open 2021 04 24;11(4):e042870. Epub 2021 Apr 24.

Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.

Objective: To assess the validity of the US Department of Health and Human Services (DHHS) definition of multimorbidity using International Classification of Diseases, ninth edition (ICD-9) codes from administrative data.

Design: Cross-sectional comparison of two ICD-9 billing code algorithms to data abstracted from medical records.

Setting: Olmsted County, Minnesota, USA.

Participants: An age-stratified and sex-stratified random sample of 1509 persons ages 40-84 years old residing in Olmsted County on 31 December 2010.

Study Measures: Seventeen chronic conditions identified by the US DHHS as important in studies of multimorbidity were identified through medical record review of each participant between 2006 and 2010. ICD-9 administrative billing codes corresponding to the 17 conditions were extracted using the Rochester Epidemiology Project records-linkage system. Persons were classified as having each condition using two algorithms: at least one code or at least two codes separated by more than 30 days. We compared the ICD-9 code algorithms with the diagnoses obtained through medical record review to identify persons with multimorbidity (defined as ≥2, ≥3 or ≥4 chronic conditions).

Results: Use of a single code to define each of the 17 chronic conditions resulted in sensitivity and positive predictive values (PPV) ≥70%, and in specificity and negative predictive values (NPV) ≥70% for identifying multimorbidity in the overall study population. PPV and sensitivity were highest in persons 65-84 years of age, whereas NPV and specificity were highest in persons 40-64 years. The results varied by condition, and by age and sex. The use of at least two codes reduced sensitivity, but increased specificity.

Conclusions: The use of a single code to identify each of the 17 chronic conditions may be a simple and valid method to identify persons who meet the DHHS definition of multimorbidity in populations with similar demographic, socioeconomic, and health care characteristics.
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http://dx.doi.org/10.1136/bmjopen-2020-042870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074567PMC
April 2021

Multimorbidity, ageing and mortality: normative data and cohort study in an American population.

BMJ Open 2021 03 19;11(3):e042633. Epub 2021 Mar 19.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

Objectives: To describe the percentile distribution of multimorbidity across age by sex, race and ethnicity, and to demonstrate the utility of multimorbidity percentiles to predict mortality.

Design: Population-based descriptive study and cohort 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 obtained the count of chronic conditions (out of 20 conditions) present on each birthday by extracting all of the diagnostic codes received in the 5 years before the index birthday from the electronic indexes of the REP. To compare each person's count to peers of same age, the counts were transformed into percentiles of the total population and displayed graphically across age by sex, race and ethnicity. In addition, quintiles 1, 2, 4 and 5 were compared with quintile 3 (reference) to predict the risk of death at 1 year, 5 years and through end of follow-up using time-to-event analyses. Follow-up was passive using the REP.

Results: We identified 238 010 persons who experienced a total of 1 458 094 birthdays during the study period (median of 6 birthdays per person; IQR 3-10). The percentiles of multimorbidity across age did not vary noticeably by sex, race or ethnicity. In general, there was an increased risk of mortality at 1 and 5 years for quintiles 4 and 5 of multimorbidity. The risk of mortality for quintile 5 was greater for younger age groups and for women.

Conclusions: The assignment of multimorbidity percentiles to persons in a population may be a simple and intuitive tool to assess relative health status, and to predict short-term mortality, especially in younger persons and in women.
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http://dx.doi.org/10.1136/bmjopen-2020-042633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986688PMC
March 2021

Moving Beyond Reflexive and Prophylactic Gynecologic Surgery.

Mayo Clin Proc 2021 02;96(2):291-294

Women's Health Research Center, Mayo Clinic, Rochester, MN; Department of Neurology, Mayo Clinic, Rochester, MN; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.

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http://dx.doi.org/10.1016/j.mayocp.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088594PMC
February 2021

Association of Premenopausal Bilateral Oophorectomy With Restless Legs Syndrome.

JAMA Netw Open 2021 02 1;4(2):e2036058. Epub 2021 Feb 1.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

Importance: Restless legs syndrome is a common neurologic disorder that is more prevalent in women than in men, and it has been suggested that female hormones may be involved in the disorder's pathophysiology.

Objective: To determine whether women who underwent premenopausal bilateral oophorectomy were at increased risk of restless legs syndrome.

Design, Setting, And Participants: This cohort study was performed using data from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2 for a population in Olmsted County, Minnesota. There were 1653 women who underwent premenopausal bilateral oophorectomy before the age of 50 years for a benign indication between 1988 and 2007 and 1653 age-matched women (of same age plus or minus 1 year) in a reference group. Follow-up was conducted until the end of the study period (ie, December 31, 2014). Data were analyzed from January to July 2020.

Exposures: Undergoing bilateral oophorectomy, as shown in medical record documentation.

Main Outcomes And Measures: Diagnosis of restless legs syndrome, as defined using Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria, was recorded.

Results: Among 3306 women, the median (interquartile range) age at baseline was 44.0 (40.0-47.0) years. Women who underwent bilateral oophorectomy, compared with women who did not undergo this procedure, had a greater number of chronic conditions at the index date (eg, 300 women [18.1%] vs 171 women [10.3%] with ≥3 chronic conditions; overall P < .001), were more likely to have obesity (576 women [34.8%] vs 442 women [27.1%]; overall P < .001), and were more likely to have a history of anemia of any type (573 women [34.7%] vs 225 women [13.6%]; P < .001), iron deficiency anemia (347 women [21.0%] vs 135 women [8.2%]; P < .001), and restless legs syndrome before the index date (32 women [1.9%] vs 14 women [0.8%]; P = .008). Women who underwent bilateral oophorectomy prior to natural menopause had a higher risk of restless legs syndrome after the index date compared with women in the reference group (120 diagnoses vs 74 diagnoses), with an adjusted hazard ratio (HR) of 1.44 (95% CI, 1.08-1.92; P = .01). After stratification by indication for the bilateral oophorectomy, there was an increased risk of restless legs syndrome among women without a benign ovarian condition (HR, 1.52; 95% CI, 1.03-2.25; P = .04) but not among women with a benign condition (HR, 1.25; 95% CI, 0.80-1.96; P = .34). Treatment with estrogen therapy through the age of 46 years in women who underwent bilateral oophorectomy at younger ages was not associated with a difference in risk.

Conclusions And Relevance: This cohort study found that risk of restless legs syndrome was increased among women who underwent bilateral oophorectomy prior to menopause, especially those without a benign ovarian indication.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.36058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851733PMC
February 2021

Reproductive history and progressive multiple sclerosis risk in women.

Brain Commun 2020 17;2(2):fcaa185. Epub 2020 Nov 17.

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.

Being a woman is one of the strongest risk factors for multiple sclerosis. The natural reproductive period from menarche to natural menopause corresponds to the active inflammatory disease period in multiple sclerosis. The fifth decade marks both the peri-menopausal transition in the reproductive aging and a transition from the relapsing-remitting to the progressive phase in multiple sclerosis. A short reproductive period with premature/early menopause and/or low number of pregnancies may be associated with an earlier onset of the progressive multiple sclerosis phase. A cross-sectional study of survey-based reproductive history in a multiple sclerosis clinical series enriched for patients with progressive disease, and a case-control study of multiple sclerosis and age/sex matched controls from a population-based cohort were conducted. Menarche age, number of complete/incomplete pregnancies, menopause type and menopause age were compared between 137 cases and 396 control females. Onset of relapsing-remitting phase of multiple sclerosis, progressive disease onset and reaching severe disability (expanded disability status scale 6) were studied as multiple sclerosis-related outcomes ( = 233). Menarche age was similar between multiple sclerosis and control females ( = 0.306). Females with multiple sclerosis had fewer full-term pregnancies than the controls ( < 0.001). Non-natural menopause was more common in multiple sclerosis (40.7%) than in controls (30.1%) ( = 0.030). Age at natural menopause was similar between multiple sclerosis (median, interquartile range: 50 years, 48-52) and controls (median, interquartile range: 51 years, 49-53) ( = 0.476). Nulliparous females had earlier age at progressive multiple sclerosis onset (mean ± standard deviation: 41.9 ± 12.5 years) than females with ≥1 full-term pregnancies (mean ± standard deviation: 47.1 ± 9.7 years) ( = 0.069) with a pregnancy-dose effect [para 0 (mean ± standard deviation: 41.9 ± 12.5 years), para 1-3 (mean ± standard deviation: 46.4 ± 9.2 years), para ≥4 (mean ± standard deviation: 52.6 ± 12.9 years) ( = 0.005)]. Menopause age was associated with progressive multiple sclerosis onset age (  = 0.359,  < 0.001). Duration from onset of relapses to onset of progressive multiple sclerosis was shorter for females with premature/early menopause ( = 26; mean ± standard deviation: 12.9 ± 9.0 years) than for females with normal menopause age ( = 39; mean ± standard deviation: 17.8 ± 10.3 years) but was longer than for males (mean  ±standard deviation: 10.0 ± 9.4 years) ( = 0.005). There was a pregnancy-dose effect of age at expanded disability status scale 6 (para 0: 43.0 ± 13.2 years, para 1-3: 51.7 ± 11.3 years, para ≥4: 53.5 ± 4.9 years) ( = 0.013). Age at menopause was associated with age at expanded disability status scale 6 (  = 0.229,  < 0.003). Premature/early menopause or nulliparity was associated with earlier onset of progressive multiple sclerosis with a 'dose effect' of pregnancies on delaying progressive multiple sclerosis and severe disability. Although causality remains uncertain, our results suggest a beneficial impact of oestrogen in delaying progressive multiple sclerosis. If confirmed in prospective studies, our findings have implications for counselling women with multiple sclerosis about pregnancy, surgical menopause and menopausal hormone therapy.
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http://dx.doi.org/10.1093/braincomms/fcaa185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772117PMC
November 2020

Association of adverse childhood experiences with menopausal symptoms: Results from the Data Registry on Experiences of Aging, Menopause and Sexuality (DREAMS).

Maturitas 2021 Jan 14;143:209-215. Epub 2020 Oct 14.

Center for Women's Health, Mayo Clinic, 200 First St SW, Rochester, MN, USA; Division of General Internal Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, USA.

Objective: To examine the association of adverse childhood experiences (ACEs) with overall menopausal symptom burden in midlife women.

Study Design: This was a cross-sectional study of women between the ages of 40 and 65 years who were seen for specialty consultation in the Menopause and Women's Sexual Health Clinic, Mayo Clinic, Rochester, MN between May 1, 2015 and December 31, 2016.

Main Outcome Measures: Participants completed the ACE questionnaire to assess childhood abuse and neglect, the Menopause Rating Scale (MRS) to assess menopausal symptom burden, the Patient Health Questionnaire (PHQ-9) to assess depression, the Generalized Anxiety Disorder questionnaire (GAD-7) to assess anxiety, and provided information on current abuse (physical, sexual and verbal/emotional).

Results: Women meeting inclusion criteria (N = 1670) had a median age of 53.7 years (interquartile range: 49.1, 58.0). Of these women, 977 (58.5 %) reported any ACE and 288 (17.2 %) reported ≥4 ACEs. As menopausal symptoms increased in severity from the first to fourth quartile, the odds ratio of ACE 1-3 (vs. 0) increased from 1 to 2.50 (trend p < 0.01), and the odds ratio of ACE ≥ 4 (vs. 0) increased from 1 to 9.61 (trend p < 0.01), a pattern that was consistent across all menopausal symptom domains. The association between severe menopausal symptoms and higher childhood adversity (ACE score 1-3 or ≥4 vs. ACE = 0) remained significant after adjusting for age, partner status, education, employment, depression, anxiety, and hormone therapy use (OR 1.84 and 4.51, p < 0.01).

Conclusion: In this large cross-sectional study, there was a significant association between childhood adversity and self-reported menopausal symptoms that persisted even after adjustment for multiple confounders. These associations highlight the importance of screening women with bothersome menopausal symptoms for childhood adversity, and of offering appropriate management and counseling for the adverse experiences, when indicated.
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http://dx.doi.org/10.1016/j.maturitas.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880696PMC
January 2021

Association of Infant Antibiotic Exposure With Childhood Health Outcomes.

Mayo Clin Proc 2021 01 16;96(1):66-77. Epub 2020 Nov 16.

Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To investigate the extent to which antibiotic exposure in the first 2 years of life is associated with the risk of immunological, metabolic, and neurobehavioral health conditions with childhood onset.

Patients And Methods: In this population-based cohort study, we identified all children born in Olmsted County, Minnesota, between January 1, 2003, and December 31, 2011, through the Rochester Epidemiology Project medical records-linkage system. Demographic characteristics, antibiotic prescriptions, and diagnostic codes through June 30, 2017, were retrieved using the Rochester Epidemiology Project infrastructure. Time-to-event analysis was performed to assess the impact of antibiotic exposure on the risk of several adverse health conditions.

Results: This study included 14,572 children (7026 girls and 7546 boys), of whom 70% (10,220) received at least 1 antibiotic prescription during the first 2 years of life. Early antibiotic exposure was associated with an increased risk of childhood-onset asthma, allergic rhinitis, atopic dermatitis, celiac disease, overweight, obesity, and attention deficit hyperactivity disorder (hazard ratios ranging from 1.20 to 2.89; P<.05 for all). The associations were influenced by the number, type, and timing of antibiotic exposure. Moreover, children exposed to antibiotics had a higher probability of having combinations of conditions, particularly when given multiple prescriptions.

Conclusion: The present study finds significant associations between early life antibiotic exposure and several distinct health conditions with childhood onset. Additional research is warranted to establish practical guidelines to optimize the benefit and minimize the risk of antibiotics in children.
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http://dx.doi.org/10.1016/j.mayocp.2020.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796951PMC
January 2021

Ascertainment of delirium status using natural language processing from electronic health records.

J Gerontol A Biol Sci Med Sci 2020 Oct 30. Epub 2020 Oct 30.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Background: Delirium is underdiagnosed in clinical practice, and is not routinely coded for billing. Manual chart review can be used to identify the occurrence of delirium, however, it is labor-intensive and impractical for large-scale studies. Natural language processing (NLP) has the capability to process raw text in electronic health records (EHRs) and determine the meaning of the information. We developed and validated NLP algorithms to automatically identify the occurrence of delirium from EHRs.

Methods: This study used a randomly selected cohort from the population-based Mayo Clinic Biobank (n=300, age>=65). We adopted the standardized evidence-based framework confusion assessment method (CAM) to develop and evaluate NLP algorithms to identify the occurrence of delirium using clinical notes in EHRs. Two NLP algorithms were developed based on CAM criteria; one based on the original CAM (NLP-CAM; delirium vs. no delirium) and another based on our modified CAM (NLP-mCAM; definite, possible, and no delirium). The sensitivity, specificity, and accuracy were used for concordance in delirium status between NLP algorithms and manual chart review as the gold standard. The prevalence of delirium cases was examined using ICD-9, NLP-CAM, and NLP-mCAM.

Results: NLP-CAM demonstrated a sensitivity, specificity and accuracy of 0.919, 1.000 and 0.967, respectively. NLP-mCAM demonstrated sensitivity, specificity and accuracy of 0.827, 0.913 and 0.827, respectively. The prevalence analysis of delirium showed that the NLP-CAM algorithm identified 12,651 (9.4%) delirium patients, the NLP-mCAM algorithm identified 20,611 (15.3%) definite delirium cases and 10,762 (8.0%) possible cases.
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http://dx.doi.org/10.1093/gerona/glaa275DOI Listing
October 2020

Epidemiology of adrenal tumours in Olmsted County, Minnesota, USA: a population-based cohort study.

Lancet Diabetes Endocrinol 2020 11;8(11):894-902

Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Adrenal tumours are commonly encountered in clinical practice, but epidemiological data mainly originate from referral centres. We aimed to determine incidence, prevalence, and rates of malignancy and hormone excess in patients with adrenal tumours in a standardised geographically well defined population.

Methods: In this retrospective population-based cohort study we assessed the standardised incidence rate of adrenal tumours in all patients with tumours who lived in Olmsted County, MN, USA, from Jan 1, 1995, to Dec 31, 2017. The Rochester Epidemiology Project infrastructure, which links medical records across all health-care providers for the entire population of Olmsted County since 1966, was used to allow researchers to identify individuals with specific diagnoses, surgical interventions, and other procedures, and to locate their medical records, which were then used in the analysis. Incidence rates and prevalence were standardised for age and sex according to the 2010 US Population.

Findings: An adrenal tumour was diagnosed in 1287 patients (median age 62 years; 713 (55·4%) were women; and 13 (1·0%) were children). Standardised incidence rates increased from 4·4 (95% CI 0·3-8·6) per 100 000 person-years in 1995 to 47·8 (36·9-58·7) in 2017, mainly because of the incidental discovery of adenomas less than 40 mm in diameter in patients older than 40 years. Prevalence of adrenal tumours in 2017 was 532 per 100 000 inhabitants, ranging from 13 per 100 000 in children (aged <18 years) to 1900 per 100 000 in patients older than 65 years. 111 (8·6%) of 1287 patients were diagnosed with malignancy (96 [7·5%] of whom has metastases), 14 (1·1%) with phaeochromocytoma, and 53 (4·1%) with overt steroid hormone excess. Malignancy was more common in children (62%) versus those older than 18 years (8%; p<0·0001), tumours discovered during cancer-staging or follow-up (43% vs 3% for incidentalomas; p<0·0001), tumours more than 40 mm in diameter (34% vs 6% for tumours <20 mm; p<0·0001), tumours with unenhanced CT attenuation of 30 Hounsfield units or more (20% vs 1% for <20 Hounsfield units; p<·0001), and bilateral masses (16% vs 7% for unilateral, p=0·0004).

Interpretation: Adrenal tumour standardised incidence rates increased 10 times from 1995 to 2017. Population-based data revealed lower rates of malignancy, phaeochromocytoma, and overt steroid hormone excess than previously reported.

Funding: National Institutes of Health.
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http://dx.doi.org/10.1016/S2213-8587(20)30314-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601441PMC
November 2020

Correction to: Neighborhood socioeconomic disadvantage is associated with multimorbidity in a geographically-defined community.

BMC Public Health 2020 09 16;20(1):1412. Epub 2020 Sep 16.

Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12889-020-09527-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495881PMC
September 2020

Difficult decisions in women at high genetic risk for cancer: toward an individualized approach.

Authors:
Walter A Rocca

Menopause 2020 07;27(7):727-729

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN; Department of Neurology, Mayo Clinic, Rochester, MN; Women's Health Research Center, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1097/GME.0000000000001572DOI Listing
July 2020

Conjugal multiple system atrophy: Be wary of implicating transmissibility.

Parkinsonism Relat Disord 2020 06 13;75:121. Epub 2020 Mar 13.

Department of Neurology, Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1016/j.parkreldis.2020.03.004DOI Listing
June 2020

Aneurysmal subarachnoid hemorrhage: long-term trends in incidence and survival in Olmsted County, Minnesota.

J Neurosurg 2020 Feb 21;134(3):878-883. Epub 2020 Feb 21.

1Department of Neurologic Surgery, and.

Objective: Recent population-based and hospital cohort studies have reported a decreasing incidence of aneurysmal subarachnoid hemorrhage (aSAH) and declining aSAH-associated case-fatality rates. Principal drivers of these trends are debated, but improvements in smoking cessation and hypertension control may be critical factors.

Methods: The population-based medical records linkage system of the Rochester Epidemiological Project was used to document aSAH incidence and 30-day case fatality rates during a 20-year study period (1996-2016) in Olmsted County, Minnesota. Incidence rates in the study period were compared with data from a previous Olmsted County study concerning aSAH incidence from 1965 to 1995 and with regional trends in tobacco use.

Results: One hundred nineteen incident cases of aSAH were included. The median age at hemorrhage was 59 years (range 16-94 years), and 74 patients were female (62.2%). The overall average annual aSAH incidence rate was 4.2/100,000 person-years (P-Y). The aSAH incidence rate decreased from 5.7/100,000 in 1996 to 3.5/100,000 P-Y in 2011-2016. The overall aSAH-associated 30-day case-fatality rate was 21.9% and declined by approximately 0.5% annually. An accelerated decline in the fatality rate (0.9%/year) was observed from 2006-2016. Smoking among adult Olmsted County residents decreased from 20.4% in 2000 to 9.1% in 2018.

Conclusions: A decline in the incidence of aSAH and 30-day case-fatality rate from 1996 to 2016 was observed, as well as an accelerated decline of the fatality rate from 2006 to 2016. These findings confirm and extend the trends reported by prior studies in the same population. The decrease in aSAH in the years studied paralleled a noticeable reduction in the population smoking rates.
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http://dx.doi.org/10.3171/2019.12.JNS192468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130583PMC
February 2020

Neighborhood socioeconomic disadvantage is associated with multimorbidity in a geographically-defined community.

BMC Public Health 2020 Jan 6;20(1):13. Epub 2020 Jan 6.

Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: Persons with low socioeconomic status may be disproportionately at risk for multimorbidity.

Methods: Adults aged ≥20 years on 4/1/2015 from 7 counties in Minnesota were identified using the Rochester Epidemiology Project (population-based sample). A composite measure of neighborhood socioeconomic disadvantage, the area deprivation index (ADI), was estimated at the census block group level (n = 251). The prevalence of 21 chronic conditions was obtained to calculate the proportion of persons with multimorbidity (≥2 chronic conditions) and severe multimorbidity (≥5 chronic conditions). Hierarchical logistic regression was used to estimate the association of ADI with multimorbidity and severe multimorbidity using odds ratios (OR).

Results: Among 198,941 persons (46.7% male, 30.6% aged ≥60 years), the age- and sex-standardized (to the United States 2010 census) median prevalence (Q1, Q3) was 23.4% (21.3%, 25.9%) for multimorbidity and 4.8% (4.0%, 5.7%) for severe multimorbidity. Compared with persons in the lowest quintile of ADI, persons in the highest quintile had a 50% increased risk of multimorbidity (OR 1.50, 95% CI 1.39-1.62) and a 67% increased risk of severe multimorbidity (OR 1.67, 95% CI 1.51-1.86) after adjusting for age, sex, race, and ethnicity. Associations were stronger after further adjustment for individual level of education; persons in the highest quintile had a 78% increased risk of multimorbidity (OR 1.78, 95% CI 1.62-1.96) and a 92% increased risk of severe multimorbidity (OR 1.92, 95% CI 1.72-2.13). There was evidence of interactions between ADI and age, between ADI and sex, and between ADI and education. After age 70 years, no difference in the risk of multimorbidity was observed across quintiles of ADI. The pattern of increasing multimorbidity with increasing ADI was more pronounced in women. Finally, there was less variability across quintiles of ADI for the most highly educated group.

Conclusions: Higher ADI was associated with increased risk of multimorbidity, and the associations were strengthened after adjustment for individual level of education, suggesting that neighborhood context plays a role in health above and beyond individual measures of socioeconomic status. Furthermore, associations were more pronounced in younger persons and women, highlighting the importance of interventions to prevent chronic conditions in younger women, in particular.
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http://dx.doi.org/10.1186/s12889-019-8123-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945427PMC
January 2020

Identifying incident Parkinson's disease using administrative diagnostic codes: a validation study.

Clin Park Relat Disord 2020 2;3. Epub 2020 Jun 2.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Background: Administrative databases that capture diagnostic codes are increasingly being used worldwide for research because they can save time and reduce costs. However, assessing validity is necessary before defining diseases using only diagnostic codes in research applications.

Objective: Our objective was to assess the validity of using diagnostic codes to identify incident Parkinson's disease (PD) cases in Olmsted County, Minnesota using an established standard for comparison (1976-2005).

Methods: Cases were identified solely using computer programs applied to administrative diagnostic code indexes from the Rochester Epidemiology Project (REP). Two codes >30 days apart or one code on the death certificate constituted PD. The standard was a clinical diagnosis by movement disorders specialists based on medical record review. Validity was assessed using positive predictive value (PPV) and sensitivity. Numbers of incident cases and incidence rates were compared between the two ascertainment methods by sex.

Results: The codes only method over-counted the number of incident PD cases by 73% (804 versus 464), and this over-counting generally increased with calendar year. Sensitivity was 80% (95% CI [76%, 84%]) and PPV was 46% (95% CI [34%, 50%]). Disease status misclassification accounted for two-thirds of falsely identified cases, where individuals were found to not have PD (43%) or even parkinsonism (23%) after medical record review. The codes only method also over-estimated the incidence rate time trend for men and women by approximately two-fold.

Conclusion: In our context, using administrative diagnostic codes only to identify incident PD cases is not recommended unless more accurate algorithms are developed.
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http://dx.doi.org/10.1016/j.prdoa.2020.100061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218579PMC
June 2020

Sex and time: A new complexity in research.

Authors:
Walter A Rocca

Maturitas 2020 05 8;135:80-81. Epub 2019 Nov 8.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address:

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http://dx.doi.org/10.1016/j.maturitas.2019.10.016DOI Listing
May 2020

Multimorbidity, functional limitations, and outcomes: Interactions in a population-based cohort of older adults.

J Comorb 2019 Jan-Dec;9:2235042X19873486. Epub 2019 Sep 9.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Objective: To understand the interaction of multimorbidity and functional limitations in determining health-care utilization and survival in older adults.

Methods: Olmsted County, Minnesota, residents aged 60-89 years in 2005 were categorized into four cohorts based on the presence or absence of multimorbidity (≥3 chronic conditions from a list of 18) and functional limitations (≥1 limitation in an activity of daily living from a list of 9), and were followed through December 31, 2016. Andersen-Gill and Cox regression estimated hazard ratios (HRs) for emergency department (ED) visits, hospitalizations, and death using persons with neither multimorbidity nor functional limitations as the reference (interaction analyses).

Results: Among 13,145 persons, 34% had neither multimorbidity nor functional limitations, 44% had multimorbidity only, 4% had functional limitations only, and 18% had both. Over a median follow-up of 11 years, 5906 ED visits, 2654 hospitalizations, and 4559 deaths occurred. Synergistic interactions on an additive scale of multimorbidity and functional limitations were observed for all outcomes; however, the magnitude of the interactions decreased with advancing age. The HR (95% confidence interval) for death among persons with both multimorbidity and functional limitations was 5.34 (4.40-6.47) at age 60-69, 4.16 (3.59-4.83) at age 70-79, and 2.86 (2.45-3.35) at age 80-89 years.

Conclusion: The risk of ED visits, hospitalizations, and death among persons with both multimorbidity and functional limitations is greater than additive. The magnitude of the interaction was strongest for the youngest age group, highlighting the importance of interventions to prevent and effectively manage multimorbidity and functional limitations early in life.
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http://dx.doi.org/10.1177/2235042X19873486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734596PMC
September 2019

Historical vignette: Leonard T. Kurland, FACE (1921-2001), the rise of neuroepidemiology, and the Rochester Epidemiology Project.

Ann Epidemiol 2019 09 2;37:1-3. Epub 2019 Aug 2.

Division of Epidemiology and the Department of Neurology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

The creation of the field of neuroepidemiology was one of the two principal professional achievements of the American College of Epidemiology Fellow Leonard T. Kurland (1921-2001), the other being the establishment of the Rochester Project. In the former, Kurland established the role of the neuroepidemiologists in the development of the corpus of knowledge needed to control and prevent the occurrence of neurological conditions. Two examples of his endeavors in this regard were his work on the Guamanian focus of neurodegenerative diseases and his seminal investigations into the epidemiology of multiple sclerosis. He was also instrumental in the development of the Rochester, Minnesota community as a population laboratory within which epidemiologic investigations could be mounted. This pioneering achievement created a resource used by many generations of epidemiologists and clinicians to examine health and disease in the population.
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http://dx.doi.org/10.1016/j.annepidem.2019.07.017DOI Listing
September 2019

Mental health conditions diagnosed before bilateral oophorectomy: a population-based case-control study.

Menopause 2019 12;26(12):1395-1404

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

Objective: We studied eight mental health conditions diagnosed before bilateral oophorectomy performed for nonmalignant indications.

Methods: We identified 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication in Olmsted County, Minnesota, during a 20-year period (1988-2007). Each woman was matched by age (±1 year) to one population-based control who had not undergone bilateral oophorectomy before the index date (age range: 21-49 years). Both cases and controls were identified using the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org). For eight mental health conditions, we calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) adjusted for race, education, and income using conditional logistic regression.

Results: Pre-existing mood disorders, anxiety disorders, and somatoform disorders were associated with increased risk of bilateral oophorectomy in overall analyses. These associations were also significant in women ≤45 years of age at index date. Personality disorders were associated with increased risk only in overall analyses and adjustment disorders only in women 46 to 49 years of age. Some of the associations were significantly different across strata by age at index date and by indication. There was also a linear trend of increasing adjusted ORs from 1.55 (95% CI 1.31-1.83) for one mental health condition to 2.19 (95% CI 1.40-3.41) for three or more conditions (trend P < 0.001).

Conclusions: We identified several mental health conditions that were associated with bilateral oophorectomy for nonmalignant indications. Awareness of these associations may guide women and physicians in future decision-making and limit unindicated bilateral oophorectomies. VIDEO SUMMARY:: http://links.lww.com/MENO/A458.
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http://dx.doi.org/10.1097/GME.0000000000001413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893116PMC
December 2019

Long-term risk of de novo mental health conditions after hysterectomy with ovarian conservation: a cohort study.

Menopause 2020 01;27(1):33-42

Department of Surgery, Mayo Clinic, Rochester, MN.

Objective: The aim of this research was to study the long-term risk of de novo mental health conditions in women who underwent hysterectomy with bilateral ovarian conservation compared with age-matched referent women.

Methods: Using the Rochester Epidemiology Project records-linkage system, we identified a historical cohort of 2,094 women who underwent hysterectomy with ovarian conservation for benign indications at age ≥18 years and with an index date between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman residing in the same county who had not undergone hysterectomy or any oophorectomy before the index date. These two cohorts were followed historically to identify de novo mental health conditions. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) using Cox proportional hazards models adjusted for 20 preexisting chronic conditions and other potential confounders. We also calculated absolute risk increases (ARIs) and reductions (ARRs) at 30 years of follow-up.

Results: Over a median follow-up of 21.9 years, women who underwent hysterectomy at any age experienced increased risks of de novo depression (adjusted HR 1.26; 95% CI, 1.12-1.41; ARI 6.6%) and anxiety (adjusted HR 1.22; 95% CI, 1.08-1.38; ARI 4.7%). The association for depression increased significantly with younger age at hysterectomy, but did not vary significantly by indication. Interactions were not significant for anxiety.

Conclusions: Hysterectomy, even with ovarian conservation, is associated with an increased long-term risk of de novo depression and anxiety, especially when performed in women who are younger. : Video Summary:http://links.lww.com/MENO/A465.
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http://dx.doi.org/10.1097/GME.0000000000001415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089568PMC
January 2020

Risk factors of neurovascular ageing in women.

J Neuroendocrinol 2020 01 3;32(1):e12777. Epub 2019 Sep 3.

Division of Epidemiology, Department of Health Sciences Research and Department of Neurology, Mayo Clinic, Rochester, MN, USA.

Biological sex and changes in sex hormones throughout life influence all aspects of health and disease. In women, changes in sex hormonal status reflect ovarian function, pregnancy and the use of exogenous hormonal treatments. Longitudinal data from defined cohorts of women will help to identify mechanisms by which the hormonal milieu contributes to cerebrovascular ageing, brain structure and ultimately cognition. This review summarises the phenotypes of three cohorts of women identified through the medical records-linkage system of the Rochester Epidemiology Project and the Mayo Clinic Specialized Center of Research Excellence (SCORE) on Sex Differences: (i) menopausal women with histories of normotensive or hypertensive pregnancies; (ii) women who had bilateral oophorectomy ≤45 years of age; and (iii) women who experienced natural menopause and used menopausal hormone treatments for 4 years. Data from these cohorts will influence the design of follow-up studies concerning how sex hormonal status affects neurovascular ageing in women.
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http://dx.doi.org/10.1111/jne.12777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982564PMC
January 2020

Prevalence of Biologically vs Clinically Defined Alzheimer Spectrum Entities Using the National Institute on Aging-Alzheimer's Association Research Framework.

JAMA Neurol 2019 Jul 15. Epub 2019 Jul 15.

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

Importance: A National Institute on Aging-Alzheimer's Association (NIA-AA) workgroup recently published a research framework in which Alzheimer disease is defined by neuropathologic or biomarker evidence of β-amyloid plaques and tau tangles and not by clinical symptoms.

Objectives: To estimate the sex- and age-specific prevalence of 3 imaging biomarker-based definitions of the Alzheimer disease spectrum from the NIA-AA research framework and to compare these entities with clinically defined diagnostic entities commonly linked with Alzheimer disease.

Design, Setting, And Participants: The Mayo Clinic Study of Aging (MCSA) is a population-based cohort study of cognitive aging in Olmsted County, Minnesota. The MCSA in-person participants (n = 4660) and passively ascertained (ie, through the medical record rather than in-person) individuals with dementia (n = 553) aged 60 to 89 years were included. Subsets underwent amyloid positron emission tomography (PET) (n = 1524) or both amyloid and tau PET (n = 576). Therefore, this study included 3 nested cohorts examined between November 29, 2004, and June 5, 2018. Data were analyzed between February 19, 2018, and March 26, 2019.

Main Outcomes And Measures: The sex- and age-specific prevalence of the following 3 biologically defined diagnostic entities was estimated: Alzheimer continuum (abnormal amyloid regardless of tau status), Alzheimer pathologic change (abnormal amyloid but normal tau), and Alzheimer disease (abnormal amyloid and tau). These were compared with the prevalence of 3 clinically defined diagnostic groups (mild cognitive impairment or dementia, dementia, and clinically defined probable Alzheimer disease).

Results: The median (interquartile range) age was 77 (72-83) years in the clinical cohort (n = 5213 participants), 77 (70-83) years in the amyloid PET cohort (n = 1524 participants), and 77 (69-83) years in the tau PET cohort (n = 576 participants). There were roughly equal numbers of women and men. The prevalence of all diagnostic entities (biological and clinical) increased rapidly with age, with the exception of Alzheimer pathologic change. The prevalence of biological Alzheimer disease was greater than clinically defined probable Alzheimer disease for women and men. Among women, these values were 10% (95% CI, 6%-14%) vs 1% (95% CI, 1%-1%) at age 70 years and 33% (95% CI, 25%-41%) vs 10% (95% CI, 9%-12%) at age 85 years (P < .001). Among men, these values were 9% (95% CI, 5%-12%) vs 1% (95% CI, 0%-1%) at age 70 years and 31% (95% CI, 24%-38%) vs 9% (95% CI, 8%-11%) at age 85 years (P < .001). The only notable difference by sex was a greater prevalence of the mild cognitive impairment or dementia clinical category among men than women.

Conclusions And Relevance: Results of this study suggest that biologically defined Alzheimer disease is more prevalent than clinically defined probable Alzheimer disease at any age and is 3 times more prevalent at age 85 years among both women and men. This difference is mostly driven by asymptomatic individuals with biological Alzheimer disease. These findings illustrate the magnitude of the consequences on public health that potentially exist by intervening with disease-specific treatments to prevent symptom onset.
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http://dx.doi.org/10.1001/jamaneurol.2019.1971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632154PMC
July 2019

Associations of Amyloid, Tau, and Neurodegeneration Biomarker Profiles With Rates of Memory Decline Among Individuals Without Dementia.

JAMA 2019 06;321(23):2316-2325

Department of Neurology, Mayo Clinic, Rochester, Minnesota.

Importance: A National Institute on Aging and Alzheimer's Association workgroup proposed a research framework for Alzheimer disease in which biomarker classification of research participants is labeled AT(N) for amyloid, tau, and neurodegeneration biomarkers.

Objective: To determine the associations between AT(N) biomarker profiles and memory decline in a population-based cohort of individuals without dementia age 60 years or older, and to determine whether biomarkers provide incremental prognostic value beyond more readily available clinical and genetic information.

Design, Setting, And Participants: Population-based cohort study of cognitive aging in Olmsted County, Minnesota, that included 480 nondemented Mayo Clinic Study of Aging participants who had a clinical evaluation and amyloid positron emission tomography (PET) (A), tau PET (T), and magnetic resonance imaging (MRI) cortical thickness (N) measures between April 16, 2015, and November 1, 2017, and at least 1 clinical evaluation follow-up by November 12, 2018.

Exposures: Age, sex, education, cardiovascular and metabolic conditions score, APOE genotype, and AT(N) biomarker profiles. Each of A, T, or (N) can be abnormal (+) or normal (-), resulting in 8 AT(N) profiles.

Main Outcomes And Measures: Primary outcome was a composite memory score measured longitudinally at 15-month intervals. Analyses measured the associations between predictor variables and the memory score, and whether AT(N) biomarker profiles significantly improved prediction of memory z score rates of change beyond a model with clinical and genetic variables only.

Results: Participants were followed up for a median of 4.8 years (interquartile range [IQR], 3.8-5.1) and 44% were women (211/480). Median (IQR) ages ranged from 67 years (65-73) in the A-T-(N)- group to 83 years (76-87) in the A+T+(N)+ group. Of the participants, 92% (441/480) were cognitively unimpaired but the A+T+(N)+ group had the largest proportion of mild cognitive impairment (30%). AT(N) biomarkers improved the prediction of memory performance over a clinical model from an R2 of 0.26 to 0.31 (P < .001). Memory declined fastest in the A+T+(N)+, A+T+(N)-, and A+T-(N)+ groups compared with the other 5 AT(N) groups (P = .002). Estimated rates of decline in the 3 fastest declining groups were -0.13 (95% CI, -0.17 to -0.09), -0.10 (95% CI, -0.16 to -0.05), and -0.10 (95% CI, -0.13 to -0.06) z score units per year, respectively, for an 85-year-old APOE ε4 noncarrier.

Conclusions And Relevance: Among older persons without baseline dementia followed for a median of 4.8 years, a prediction model that included amyloid PET, tau PET, and MRI cortical thickness resulted in a small but statistically significant improvement in predicting memory decline over a model with more readily available clinical and genetic variables. The clinical importance of this difference is uncertain.
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http://dx.doi.org/10.1001/jama.2019.7437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582267PMC
June 2019

Frequency and predictors of the potential overprescribing of antidepressants in elderly residents of a geographically defined U.S. population.

Pharmacol Res Perspect 2019 02 23;7(1):e00461. Epub 2019 Jan 23.

Department of Psychiatry & Psychology Mayo Clinic Rochester Minnesota.

The purpose of this study was to estimate the extent of potential antidepressant overprescribing in a geographically defined U.S. population, and to determine the indications and factors that account for it. We conducted a cohort study of new antidepressant prescriptions for elderly residents of Olmsted County, Minnesota, 2005-2012, using the Rochester Epidemiology Project medical records-linkage system. Indications for antidepressants were abstracted from health records for all cohort members. Potential antidepressant overprescribing was defined based on regulatory approval, the level of evidence identified from a standardized drug information database, and multidisciplinary expert review. Predictors of potential antidepressant overprescribing were investigated using logistic regression models, stratified by general antidepressant indication (general medical indication, specific psychiatric diagnosis, and non-specific psychiatric symptoms). Potential antidepressant overprescribing occurred in 24% of 3199 incident antidepressant prescriptions during the study period, and involved primarily newer antidepressants that were prescribed for non-specific psychiatric symptoms and subthreshold diagnoses. Potential antidepressant overprescribing was associated with nursing home residence, having a higher number of comorbid medical conditions and outpatient prescribers, taking more concomitant medications, having greater use of urgent or acute care services in the year preceding the index antidepressant prescription, and being prescribed antidepressants via telephone, e-mail, or patient portal. In conclusion, potential antidepressant overprescribing occurred in elderly persons and involved mainly newer antidepressants used for non-specific psychiatric symptoms and subthreshold diagnoses, and was associated with indicators of higher clinical complexity or severity and with prescribing without face-to-face patient contact.
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http://dx.doi.org/10.1002/prp2.461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344796PMC
February 2019

Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy.

Menopause 2018 11;25(11):1275-1285

Divisions of Epidemiology.

Objective: We studied the long-term risk of depressive and anxiety symptoms in women who underwent bilateral oophorectomy before menopause.

Design: We conducted a cohort study among all women residing in Olmsted County, MN, who underwent bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the bilateral oophorectomy cohort was matched by age with a referent woman from the same population who had not undergone an oophorectomy. In total, we studied 666 women with bilateral oophorectomy and 673 referent women. Women were followed for a median of 24 years, and depressive and anxiety symptoms were assessed using a structured questionnaire via a direct or proxy telephone interview performed from 2001 through 2006.

Results: Women who underwent bilateral oophorectomy before the onset of menopause had an increased risk of depressive symptoms diagnosed by a physician (hazard ratio = 1.54, 95% CI: 1.04-2.26, adjusted for age, education, and type of interview) and of anxiety symptoms (adjusted hazard ratio = 2.29, 95% CI: 1.33-3.95) compared with referent women. The findings remained consistent after excluding depressive or anxiety symptoms that first occurred within 10 years after oophorectomy. The associations were greater with younger age at oophorectomy but did not vary across indications for the oophorectomy. In addition, treatment with estrogen to age 50 years in women who underwent bilateral oophorectomy at younger ages did not modify the risk.

Conclusions: Bilateral oophorectomy performed before the onset of menopause is associated with an increased long-term risk of depressive and anxiety symptoms.
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http://dx.doi.org/10.1097/GME.0000000000001229DOI Listing
November 2018

Association of Bilateral Salpingo-Oophorectomy Before Menopause Onset With Medial Temporal Lobe Neurodegeneration.

JAMA Neurol 2019 01;76(1):95-100

Department of Radiology, Mayo Clinic, Rochester, Minnesota.

Importance: There is an increased risk of cognitive impairment or dementia in women who undergo bilateral salpingo-oophorectomy (BSO) before menopause. However, data are lacking on the association of BSO before menopause with imaging biomarkers that indicate medial temporal lobe neurodegeneration and Alzheimer disease pathophysiology.

Objective: To investigate medial temporal lobe structure, white matter lesion load, and β-amyloid deposition in women who underwent BSO before age 50 years and before reaching natural menopause.

Design, Setting, And Participants: This nested case-control study of women in the population-based Mayo Clinic Cohort Study of Oophorectomy and Aging-2 (MOA-2) and in the Mayo Clinic Study of Aging (MCSA) in Olmsted County, Minnesota, included women who underwent BSO from 1988 through 2007 and a control group from the intersection of the 2 cohorts. Women who underwent BSO and control participants who underwent a neuropsychological evaluation, magnetic resonance imaging (MRI), and Pittsburgh compound B positron emission tomography (PiB-PET) were included in the analysis. Data analysis was performed from November 2017 to August 2018.

Exposure: Bilateral salpingo-oophorectomy in premenopausal women who were younger than 50 years.

Main Outcomes And Measures: Cortical β-amyloid deposition on PiB-PET scan was calculated using the standard uptake value ratio. White matter hyperintensity volume and biomarkers for medial temporal lobe neurodegeneration (eg, amygdala volume, hippocampal volume, and parahippocampal-entorhinal cortical thickness) on structural MRI and entorhinal white matter fractional anisotropy on diffusion tensor MRI were also measured.

Results: Forty-one women who underwent BSO and 49 control participants were recruited. One woman was excluded from the BSO group after diagnosis of an ovarian malignant condition, and 6 women were excluded from the control group after undergoing BSO after enrollment. Twenty control participants and 23 women who had undergone BSO completed all examinations. The median (interquartile range [IQR]) age at imaging was 65 (62-68) years in the BSO group and 63 (60-66) years in the control group. Amygdala volume was smaller in the BSO group (median [IQR], 1.74 [1.59-1.91] cm3) than the control group (2.15 [2.05-2.37] cm3; P < .001). The parahippocampal-entorhinal cortex was thinner in the BSO group (median [IQR], 3.91 [3.64-4.00] mm) than the control group (3.97 [3.89-4.28] mm; P = .046). Entorhinal white matter fractional anisotropy was lower in the BSO group (median [IQR], 0.19 [0.18-0.22]) than the control group (0.22 [0.20-0.23]; P = .03). Women were treated with estrogen in both groups (BSO, n = 22 of 23 [96%]; control, n = 10 of 19 [53%]). Global cognitive status test results did not differ between the groups.

Conclusions And Relevance: Abrupt hormonal changes associated with BSO in premenopausal women may lead to medial temporal lobe structural abnormalities later in life. Longitudinal evaluation is needed to determine whether cognitive decline follows.
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http://dx.doi.org/10.1001/jamaneurol.2018.3057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439881PMC
January 2019
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