INTRODUCTION Reducing racial/ethnic disparities is a primary objective of the National Alzheimer’s Plan (NAPA), yet direct comparisons within large samples representing diversity of the United States are lacking. METHODS Dementia incidence from 1/1/2000-12/31/2013 and 25-year cumulative risk in 274,283 healthcare members aged 64+ (n=18,778 African-American, n=4,543 American Indian/Alaska Native (AIAN), n=21,000 Latino, n=440 Pacific Islander, n=206,490 White, n=23,032 Asian-Americans). Cox proportional hazard models were adjusted for age, sex, medical utilization, and comorbidities. RESULTS Dementia incidence (N=59,555) was highest for African-Americans (26.6/1,000 person-years) and AIANs (22.2/1,000 person-years); intermediate for Latinos (19.6/1,000 person-years), Pacific Islanders (19.6/1,000 person-years), and Whites (19.3/1,000 person-years); and lowest among Asian-Americans (15.2/1,000 person-years). Risk was 65% greater for African-Americans (hazard ratio=1.65; 95% confidence interval=1.58-1.72) versus Asian-Americans. Cumulative 25-year risk at age 65 was: 38% African-Americans, 35% AIANs, 32% Latino, 25% Pacific Islanders, 30% White, and 28% Asian-Americans. DISCUSSION Dementia rates varied over 60% between groups, providing a comprehensive benchmark for the NAPA goal of reducing disparities.

OBJECTIVEChronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.RESEARCH DESIGN AND METHODSWe examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998–1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.RESULTSIndividuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10–6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.CONCLUSIONSWe demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.

Objective To evaluate trials of drugs that target amyloid to determine whether reductions in amyloid levels are likely to improve cognition. Design Instrumental variable meta-analysis. Setting 14 randomized controlled trials of drugs for the prevention or treatment of Alzheimer’s disease that targeted an amyloid mechanism, identified from ClinicalTrials.gov. Population Adults enrolled in randomized controlled trials of amyloid targeting drugs. Inclusion criteria for trials vary, but typically include adults aged 50 years or older with a diagnosis of mild cognitive impairment or Alzheimer’s disease, and amyloid positivity at baseline. Main outcome measures Analyses included trials for which information could be obtained on both change in brain amyloid levels measured with amyloid positron emission tomography and change in at least one cognitive test score reported for each randomization arm. Results Pooled results from the 14 randomized controlled trials were more precise than estimates from any single trial. The pooled estimate for the effect of reducing amyloid levels by 0.1 standardized uptake value ratio units was an improvement in the mini-mental state examination score of 0.03 (95% confidence interval −0.06 to 0.1) points. This study provides a web application that allows for the re-estimation of the results when new data become available and illustrates the magnitude of the new evidence that would be necessary to achieve a pooled estimate supporting the benefit of reducing amyloid levels. Conclusions Pooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.

Background/Objective Higher late life body mass index (BMI) is unrelated to or even predicts lower risk of dementia in late-life, a phenomenon that may be explained by reverse causation due to weight loss during pre-clinical phases of dementia. We aim to investigate the association of baseline BMI and changes in BMI with dementia in a large prospective cohort, and to examine whether weight loss predicts cognitive function. Methods Using a national cohort of adults average age 58 at baseline in 1994 (n=7,029), we investigated the associations between baseline BMI in 1994 and memory scores from 2000 to 2010. We also examined the association of BMI change from 1994 to 1998 with memory scores from 2000 to 2010. Lastly, to investigate reverse causation, we examined whether memory scores in 1996 predicted BMI trajectories from 2000 to 2010. Results Baseline overweight predicted better memory scores 6 to 16 years later (β=0.012, 95%CI=0.001; 0.023). Decline in BMI predicted lower memory scores over the subsequent 12 years (β= −0.026, 95%CI= −0.041; −0.011). Lower memory scores at mean age 60 in 1996 predicted faster annual rate of BMI decline during follow-up (β= −0.158 kg/m2 per year, 95% CI= −0.223;−0.094). Conclusion Consistent with reverse causation, greater decline in BMI over the first four years of the study was associated with lower memory scores over the next decade and lower memory scores was associated with a decline in BMI. These findings suggest that pre-clinical dementia predicts weight loss for people as early as their late 50s.

Background This study was conducted to compare oral contraceptive (OC) pharmacokinetics (PK) in normal weight (BMI 19.0-24.9) and obese (BMI 30.0-39.9) women. Study Design During the third week of the third cycle of OC use, we admitted 15 normal weight and 15 obese women for collection of 12 venous specimens over 24 h. Using RIA techniques, we measured levels of ethinyl estradiol (EE) and levonorgestrel (LNG). During the same cycle, women underwent twice-weekly sonography to assess ovarian follicular development and blood draws to measure endogenous estradiol (E2) and progesterone levels. Results Obese women had a lower area under the curve (AUC; 1077.2 pg*h/mL vs 1413.7 pg*h/mL) and lower maximum values (85.7 pg/mL vs 129.5 pg/mL) for EE than normal weight women (p = 0.04 and 0.01, respectively); EE trough levels were similar between BMI groups. The similar, but smaller, differences in their LNG levels for AUC and maximum values (Cmax) were not statistically significant. While peak values differed somewhat, the LNG trough levels were similar for obese and normal weight women (2.6 ng/mL and 2.5 ng/mL, respectively). Women with greater EE AUC had smaller follicular diameters (p = 0.05) and lower E2 levels (p = 0.04). While follicular diameters tended to be larger among obese women, these differences were not statistically significant. Conclusion OC hormone peak levels are lower among obese women compared to normal weight women, but their trough levels are similar. In this small study, the observed PK differences did not translate into more ovarian follicular activity among obese OC users.