Category: Internal Medicine

Hot Topics: Gum Disease a Warning Sign for Diabetes

Teeuw WJ, Kosho MXF, Poland DCW, Gerdes VEA, Loos BG. Periodontitis as a possible early sign of diabetes mellitus. BMJ Open Diab Res Care. 2017;5(1). http://dx.doi.org/10.1136/bmjdrc-2016-000326.

Objective The early diagnosis of (pre)diabetes mellitus is essential for the prevention of diabetes complications. It has been suggested that gum disease (periodontitis) might be an early complication of diabetes and may be a useful risk indicator for diabetes screening. Therefore, a dental office could be a good location for screening for (pre)diabetes in patients with periodontitis using a validated glycated hemoglobin (HbA1c) dry spot analysis.

Research design and methods A total of 313 individuals from a university dental clinic participated. From 126 patients with mild/moderate periodontitis, 78 patients with severe periodontitis and 109 subjects without periodontitis, HbA1c values were obtained by the analysis of dry blood spots. Differences in mean HbA1c values and the prevalence of (pre)diabetes between the groups were analyzed.

Results The mild/moderate and severe periodontitis groups showed significantly higher HbA1c values (6.1%±1.4% (43 mmol/mol±15 mmol/mol) and 6.3%±1.3% (45 mmol/mol±15 mmol/mol), respectively) compared with the control group (5.7%±0.7% (39 mmol/mol±8 mmol/mol), p=0.003). In addition, according to the American Diabetes Association (ADA) guidelines for diagnosis, there was a significant over-representation of subjects with suspected diabetes (23% and 14%) and pre-diabetes (47% and 46%) in the severe periodontitis group and mild/moderate periodontitis groups, respectively, compared with the control group (10% and 37%, p=0.010). Notably, 18.1% of patients with suspected new diabetes were found among subjects with severe periodontitis compared with 9.9% and 8.5% among subjects with mild/moderate periodontitis and controls, respectively (p=0.024).

Conclusions The dental office, with particular focus on patients with severe periodontitis, proved to be a suitable location for screening for (pre)diabetes; a considerable number of suspected new diabetes cases were identified. The early diagnosis and treatment of (pre)diabetes help to prevent more severe complications and benefit the treatment of periodontitis.

Posted in Diabetes, Hot Topics in Research

Hot Topics: Stem Cell Transplants May Slow Progression of Multiple Sclerosis

Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Muraro PA, Pasquini M, Atkins HL,et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurology. 2017. http://dx.doi.org/10.1001/jamaneurol.2016.5867.

Importance  Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies.

Objective  To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.

Design, Setting, and Participants  Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015.

Exposures  Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen.

Main Outcomes and Measures  The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models.

Results  Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95).

Conclusions and Relevance  In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.

Posted in Hot Topics in Research, Neurology

Hot Topics: Financial Concerns Hinder Younger Cancer Survivors’ Treatment Compliance

Do cancer survivors change their prescription drug use for financial reasons? Findings from a nationally representative sample in the United States

Zheng Z, Han X, Guy GP, et al. Do cancer survivors change their prescription drug use for financial reasons? Findings from a nationally representative sample in the United States. Cancer. 2017:n/a-n/a. http://dx.doi.org/10.1002/cncr.30560.

BACKGROUND
There is limited evidence from nationally representative samples about changes in prescription drug use for financial reasons among cancer survivors in the United States.
METHODS
The 2011 to 2014 National Health Interview Survey was used to identify adults who reported ever having been told they had cancer (cancer survivors; n = 8931) and individuals without a cancer history (n = 126,287). Measures of changes in prescription drug use for financial reasons included: 1) skipping medication doses, 2) taking less medicine, 3) delaying filling a prescription, 4) asking a doctor for lower cost medication, 5) buying prescription drugs from another country, and 6) using alternative therapies. Multivariable logistic regression analyses were controlled for demographic characteristics, number of comorbid conditions, interactions between cancer history and number of comorbid conditions, and health insurance coverage. Main analyses were stratified by age (nonelderly, ages 18-64 years; elderly, ages ≥65 years) and time since diagnosis (recently diagnosed, <2 years; previously diagnosed, ≥2 years).
RESULTS
Among nonelderly individuals, both recently diagnosed (31.6%) and previously diagnosed (27.9%) cancer survivors were more likely to report any change in prescription drug use for financial reasons than those without a cancer history (21.4%), with the excess percentage changes for individual measures ranging from 3.5% to 9.9% among previously diagnosed survivors and from 2.6% to 2.7% among recently diagnosed survivors (P < .01). Elderly cancer survivors and those without a cancer history had comparable rates of changes in prescription drug use for financial reasons.
CONCLUSIONS
Nonelderly cancer survivors are particularly vulnerable to changes in prescription drug use for financial reasons, suggesting that targeted efforts are needed. Cancer 2017. © 2017 American Cancer Society.
Posted in Hot Topics in Research, Oncology

Hot Topics: Larger Racial Disparity in Cervical Cancer Gap Than Previously Estimated

Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States

Beavis AL, Gravitt PE, Rositch AF. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017. http://dx.doi.org/10.1002/cncr.30507.

BACKGROUND
The objectives of this study were to determine the age-standardized and age-specific annual US cervical cancer mortality rates after correction for the prevalence of hysterectomy and to evaluate disparities by age and race.

METHODS
Estimates for deaths due to cervical cancer stratified by age, state, year, and race were derived from the National Center for Health Statistics county mortality data (2000-2012). Equivalently stratified data on the prevalence of hysterectomy for women 20 years old or older from the Behavioral Risk Factor Surveillance System survey were used to remove women who were not at risk from the denominator. Age-specific and age-standardized mortality rates were computed, and trends in mortality rates were analyzed with Joinpoint regression.

RESULTS
Age-standardized rates were higher for both races after correction. For black women, the corrected mortality rate was 10.1 per 100,000 (95% confidence interval [CI], 9.6-10.6), whereas the uncorrected rate was 5.7 per 100,000 (95% CI, 5.5-6.0). The corrected rate for white women was 4.7 per 100,000 (95% CI, 4.6-4.8), whereas the uncorrected rate was 3.2 per 100,000 (95% CI, 3.1-3.2). Without the correction, the disparity in mortality between races was underestimated by 44%. Black women who were 85 years old or older had the highest corrected rate: 37.2 deaths per 100,000. A trend analysis of corrected rates demonstrated that white women’s rates decreased at 0.8% per year, whereas the annual decrease for black women was 3.6% (P < .05).

CONCLUSIONS
A correction for hysterectomy has revealed that cervical cancer mortality rates are underestimated, particularly in black women. The highest rates are seen in the oldest black women, and public health efforts should focus on appropriate screening and adequate treatment in this population. Cancer 2017. © 2017 American Cancer Society.

Posted in Front Page, Hot Topics in Research, Oncology

Hot Topics: New Free Database Crowdsources Cancer Mutation Research

CIViC is a Community Knowledgebase for Expert Crowdsourcing the Clinical Interpretation of Variants in Cancer

Griffith M, Spies NC, Krysiak K, et al. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nat Genet. 2017;49(2):170-174. http://dx.doi.org/10.1038/ng.3774.

CIViC is an expert-crowdsourced knowledgebase for Clinical Interpretation of Variants in Cancer describing the therapeutic, prognostic, diagnostic and predisposing relevance of inherited and somatic variants of all types. CIViC is committed to open-source code, open-access content, public application programming interfaces (APIs) and provenance of supporting evidence to allow for the transparent creation of current and accurate variant interpretations for use in cancer precision medicine.

Posted in Front Page, Hot Topics in Research, Oncology

Hot Topics: Women in Poverty More at Risk for Heart Attacks Than Men

Sex differences in the relationship between socioeconomic status and cardiovascular disease: A systematic review and meta-analysis

Backholer K, Peters SAE, Bots SH, Peeters A, Huxley RR, Woodward M. Sex differences in the relationship between socioeconomic status and cardiovascular disease: A systematic review and meta-analysis. Journal of Epidemiology and Community Health. 2016. http://dx.doi.org/10.1136/jech-2016-207890.

Background Low socioeconomic status (SES) is a known risk factor for cardiovascular disease (CVD) but whether its effects are comparable in women and men is unknown.

Methods PubMed MEDLINE was systematically searched. Studies that reported sex-specific estimates, and associated variability, of the relative risk (RR) for coronary heart disease (CHD), stroke or CVD according to a marker of SES (education, occupation, income or area of residence), for women and men were included. RRs were combined with those derived from cohort studies using individual participant data. Data were pooled using random effects meta-analyses with inverse variance weighting. Estimates of the ratio of the RRs (RRR), comparing women with men, were computed.

Results Data from 116 cohorts, over 22 million individuals, and over 1 million CVD events, suggest that lower SES is associated with increased risk of CHD, stroke and CVD in women and men. For CHD, there was a significantly greater excess risk associated with lower educational attainment in women compared with men; comparing lowest with highest levels, the age-adjusted RRR was 1.24 (95% CI 1.09 to 1.41) and the multiple-adjusted RRR was 1.34 (1.09 to 1.63). For stroke, the age-adjusted RRR was 0.93 (0.72 to 1.18), and the multiple-adjusted was RRR 0.79 (0.53 to 1.19). Corresponding results for CVD were 1.18 (1.03 to 1.36), 1.23 (1.03 to 1.48), respectively. Similar results were observed for other markers of SES for all three outcomes.

Conclusions Reduction of socioeconomic inequalities in CHD and CVD outcomes might require different approaches for men and women.

Posted in Cardiology, Front Page, Hot Topics in Research

Hot Topics: Bed Cycling Safe for ICU Patients

TryCYCLE: A Prospective Study of the Safety and Feasibility of Early In-Bed Cycling in Mechanically Ventilated Patients

Kho ME, Molloy AJ, Clarke FJ, et al. TryCYCLE: A prospective study of the safety and feasibility of early in-bed cycling in mechanically ventilated patients. PLOS ONE. 2016;11(12):e0167561.

Introduction

The objective of this study was to assess the safety and feasibility of in-bed cycling started within the first 4 days of mechanical ventilation (MV) to inform a future randomized clinical trial.

Methods

We conducted a 33-patient prospective cohort study in a 21-bed adult academic medical-surgical intensive care unit (ICU) in Hamilton, ON, Canada. We included adult patients (≥ 18 years) receiving MV who walked independently pre-ICU. Our intervention was 30 minutes of in-bed supine cycling 6 days/week in the ICU. Our primary outcome was Safety (termination), measured as events prompting cycling termination; secondary Safety (disconnection or dislodgement) outcomes included catheter/tube dislodgements. Feasibility was measured as consent rate and fidelity to intervention. For our primary outcome, we calculated the binary proportion and 95% confidence interval (CI).

Results

From 10/2013-8/2014, we obtained consent from 34 of 37 patients approached (91.9%), 33 of whom received in-bed cycling. Of those who cycled, 16(48.4%) were female, the mean (SD) age was 65.8(12.2) years, and APACHE II score was 24.3(6.7); 29(87.9%) had medical admitting diagnoses. Cycling termination was infrequent (2.0%, 95% CI: 0.8%-4.9%) and no device dislodgements occurred. Cycling began a median [IQR] of 3 [2, 4] days after ICU admission; patients received 5 [3, 8] cycling sessions with a median duration of 30.7 [21.6, 30.8] minutes per session. During 205 total cycling sessions, patients were receiving invasive MV (150 [73.1%]), vasopressors (6 [2.9%]), sedative or analgesic infusions (77 [37.6%]) and dialysis (4 [2.0%]).

Conclusions

Early cycling within the first 4 days of MV among hemodynamically stable patients is safe and feasible. Research to evaluate the effect of early cycling on patient function is warranted.

Posted in Critical Care, Hot Topics in Research, January, Physical Therapy

Hot Topics: Lifestyle Makes a Difference in Heart Disease

Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease

Khera AV, Emdin CA, Drake I, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med. 2016;375(24):2349-2358. http://dx.doi.org/10.1056/NEJMoa1605086.

BACKGROUND
Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown.

METHODS
Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts — 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women’s Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) — and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet.

RESULTS
The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval [CI], 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category.

CONCLUSIONS
Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle. (Funded by the National Institutes of Health and others.)

Posted in Cardiology, Hot Topics in Research, Internal Medicine, January

Hot Topics: Experimental Ebola Vaccine Gives 100% Protection

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!)

Henao-Restrepo A, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing ebola virus disease: Final results from the guinea ring vaccination, open-label, cluster-randomised trial (ebola ça suffit!). The Lancet. http://dx.doi.org/10.1016/S0140-6736(16)32621-6.

Background
rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.

Methods
We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6–17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.

Findings
In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3–100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae.

Interpretation
The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters.

Henao-Restrepo A, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing ebola virus disease: Final results from the guinea ring vaccination, open-label, cluster-randomised trial (ebola ça suffit!). The Lancet. http://dx.doi.org/10.1016/S0140-6736(16)32621-6.

Posted in Hot Topics in Research, Infectious Disease, Internal Medicine, January

A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012

A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012

Importance  The aging of the US population is expected to lead to a large increase in the number of adults with dementia, but some recent studies in the United States and other high-income countries suggest that the age-specific risk of dementia may have declined over the past 25 years. Clarifying current and future population trends in dementia prevalence and risk has important implications for patients, families, and government programs.

Objective  To compare the prevalence of dementia in the United States in 2000 and 2012.

Design, Setting, and Participants  We used data from the Health and Retirement Study (HRS), a nationally representative, population-based longitudinal survey of individuals in the United States 65 years or older from the 2000 (n = 10 546) and 2012 (n = 10 511) waves of the HRS.

Main Outcomes and Measures  Dementia was identified in each year using HRS cognitive measures and validated methods for classifying self-respondents, as well as those represented by a proxy. Logistic regression was used to identify socioeconomic and health variables associated with change in dementia prevalence between 2000 and 2012.

Results  The study cohorts had an average age of 75.0 years (95% CI, 74.8-75.2 years) in 2000 and 74.8 years (95% CI, 74.5-75.1 years) in 2012 (P = .24); 58.4% (95% CI, 57.3%-59.4%) of the 2000 cohort was female compared with 56.3% (95% CI, 55.5%-57.0%) of the 2012 cohort (P < .001). Dementia prevalence among those 65 years or older decreased from 11.6% (95% CI, 10.7%-12.7%) in 2000 to 8.8% (95% CI, 8.2%-9.4%) (8.6% with age- and sex-standardization) in 2012 (P < .001). More years of education was associated with a lower risk for dementia, and average years of education increased significantly (from 11.8 years [95% CI, 11.6-11.9 years] to 12.7 years [95% CI, 12.6-12.9 years]; P < .001) between 2000 and 2012. The decline in dementia prevalence occurred even though there was a significant age- and sex-adjusted increase between years in the cardiovascular risk profile (eg, prevalence of hypertension, diabetes, and obesity) among older US adults.

Conclusions and Relevance  The prevalence of dementia in the United States declined significantly between 2000 and 2012. An increase in educational attainment was associated with some of the decline in dementia prevalence, but the full set of social, behavioral, and medical factors contributing to the decline is still uncertain. Continued monitoring of trends in dementia incidence and prevalence will be important for better gauging the full future societal impact of dementia as the number of older adults increases in the decades ahead.

 

Kenneth M. Langa, MD, PhD1,2,3,4; Eric B. Larson, MD, MPH5; Eileen M. Crimmins, PhD6; et alJessica D. Faul, PhD3; Deborah A. Levine, MD, MPH; Mohammed U. Kabeto, MS; David R. Weir, PhD 
JAMA Intern Med. Published online November 21, 2016. doi:10.1001/jamainternmed.2016.6807
Posted in Alzheimer Disease, December, Dementia, Hot Topics in Research