Faculty Bibliography

AIMS/HYPOTHESIS:The aim of this work was to evaluate whether the association of prediabetes with dementia is explained by the intervening onset of diabetes. METHODS:39-46 mmol/mol (5.7-6.4%) and subsequent incident diabetes as a self-reported physician diagnosis or use of diabetes medication. Incident dementia was ascertained via active surveillance and adjudicated. We quantified the association of prediabetes with dementia risk before and after accounting for the subsequent development of diabetes among ARIC participants without diabetes at baseline (1990-1992; participants aged 46-70 years). We also evaluated whether age at diabetes diagnosis modified the risk of dementia. RESULTS:Among 11,656 participants without diabetes at baseline, 2330 (20.0%) had prediabetes. Before accounting for incident diabetes, prediabetes was significantly associated with the risk of dementia (HR 1.12 [95% CI 1.01, 1.24]). After accounting for incident diabetes, the association was attenuated and non-significant (HR 1.05 [95% CI 0.94, 1.16]). Earlier age of onset of diabetes had the strongest association with dementia: HR 2.92 (95% CI 2.06, 4.14) for onset before 60 years; HR 1.73 (95% CI 1.47, 2.04) for onset at 60-69 years; and HR 1.23 (95% CI 1.08, 1.40) for onset at 70-79 years. CONCLUSIONS/INTERPRETATION:Prediabetes is associated with dementia risk but this risk is explained by the subsequent development of diabetes. Earlier age of onset of diabetes substantially increases dementia risk. Preventing or delaying progression of prediabetes to diabetes will reduce dementia burden.

INTRODUCTION:The fraction of dementia attributable to hypertension might vary depending on the age of the population considered and the age through which dementia occurs. METHODS:In the Atherosclerosis Risk in Communities study, we quantified population attributable fractions (PAF) of dementia by age 80 and 90 from hypertension assessed at ages of 45-54 (n = 7572), 55-64 (n = 12,033), 65-74 (n = 6561), and 75-84 (n = 2086). RESULTS:The PAF for dementia by age 80 from all non-normal blood pressure at ages 45-54 was 15.3% (95% confidence interval [CI] = 6.9%-22.3%), 19.1% (95% CI = 9.9%-26.9%) at ages 55-64, and 19.9% (95% CI = -4.4%-38.5%) at ages 65-74. The strongest PAFs were from stage 2 hypertension (11.9%-21.3%). For dementia by age 90, PAFs from non-normal blood pressure up through age 75 were smaller (10.9%-13.8%), and non-significant by age 75-84. DISCUSSION:Interventions targeting hypertension even in early late life might reduce a sizeable proportion of dementia. HIGHLIGHTS:We estimated prospective population attributable risks of dementia for hypertension. 15%-20% of dementia cases by age 80 are from non-normal blood pressure (BP). Associations between hypertension and dementia persisted through age 75. Midlife to early late-life BP control might reduce a large proportion of dementia.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Older adults initiating dialysis have a high risk of mortality and that risk may be related to potentially inappropriate medications (PIMs). Our objective was to identify and validate mortality risk associated with American Geriatrics Society Beers Criteria PIM classes and concomitant PIM use. METHODS:We used US Renal Data System data to establish a cohort of adults aged ≥ 65 years initiating dialysis (2013-2014) and had no PIM prescriptions in the 6 months prior to dialysis initiation. In a development cohort (40% sample), adjusted Cox proportional hazards models were performed to determine which of 30 PIM classes were associated with mortality (or "high-risk" PIMs). Adjusted Cox models were performed to assess the association of the number of "high-risk" PIM fills/month with mortality. All models were repeated in the validation cohort (60% sample). RESULTS:In the development cohort (n = 15,570), only 13 of 30 PIM classes were associated with a higher mortality risk. Compared with those with no "high-risk" PIM fills/month, patients having one "high-risk" PIM fill/month had a 1.29-fold (95% confidence interval 1.21-1.38) increased risk of death; those with two or more "high-risk" PIM fills/month had a 1.40-fold (95% confidence interval 1.24-1.58) increased risk. These findings were similar in the validation cohort (n = 23,569). CONCLUSIONS:Only a minority of Beers Criteria PIM classes may be associated with mortality in the older dialysis population; however, mortality risk increases with concomitant use of "high-risk" PIMs. Additional studies are needed to confirm these associations and their underlying mechanisms.

Approximately half of the brain's circuits are involved in vision and control of eye movements. Therefore, visual dysfunction is a common symptom of concussion, the mildest form of traumatic brain injury (TBI). Photosensitivity, vergence dysfunction, saccadic abnormalities, and distortions in visual perception have been reported as vision-related symptoms following concussion. Impaired visual function has also been reported in populations with a lifetime history of TBI. Consequently, vision-based tools have been developed to detect and diagnose concussion in the acute setting, and characterize visual and cognitive function in those with a lifetime history of TBI. Rapid automatized naming (RAN) tasks have provided widely accessible and quantitative measures of visual-cognitive function. Laboratory-based eye tracking approaches demonstrate promise in measuring visual function and validating results from RAN tasks in patients with concussion. Optical coherence tomography (OCT) has detected neurodegeneration in patients with Alzheimer's disease and multiple sclerosis and may provide critical insight into chronic conditions related to TBI, such as traumatic encephalopathy syndrome. Here, we review the literature and discuss the future directions of vision-based assessments of concussion and conditions related to TBI.

OBJECTIVES:3,4-Methylenedioxymethamphetamine (MDMA) (also known as "ecstasy" or "Molly") has regained attention in recent years for its efficacy in treating posttraumatic stress disorder, and the drug was granted breakthrough therapy designation for such use by the US Food and Drug Administration in 2017. However, little is known about the current epidemiology of recreational ecstasy/MDMA use. METHODS:We estimated past-year prevalence and correlates of ecstasy/MDMA use based on a representative sample of noninstitutionalized US individuals 12 years or older from the 2015-2020 National Survey on Drug Use and Health (N = 315,661). RESULTS:An estimated 0.9% (95% confidence interval [CI] = 0.9-1.0) of individuals used ecstasy/MDMA in the past year. Compared with those ages 35-49 years, all younger age groups were at increased odds for use, while those older than 50 years (adjusted odds ratio [aOR] = 0.14, 95% CI = 0.08-0.23) were at low odds for use. Compared with heterosexual men, those identifying as bisexual women (aOR = 1.32, 95% CI = 1.02-1.72) were at increased odds for use, and compared with White individuals, those identifying as Asian (aOR = 1.92, 95% CI = 1.42-2.59), Black (aOR = 1.70, 95% CI = 1.41-2.06), or multiracial (aOR = 1.61, 95% CI = 1.19-2.16) were at increased odds for use. Past-year use of other drugs (e.g., cannabis, ketamine), prescription drug misuse (e.g., pain relievers, stimulants), nicotine dependence (aOR = 1.21, 95% CI = 1.00-1.45), and alcohol use disorder (aOR = 1.41, 95% CI = 1.25-1.58) were also associated with increased odds for use. CONCLUSIONS:While use of ecstasy/MDMA continues to be relatively rare, findings from this study can help inform prevention and harm reduction strategies, especially among certain subpopulations that are at high risk for use.

Incarceration among Black sexual minority men and Black transgender women (BSMM/BTW) is disproportionately high in the United States. Limited research has documented the disruptive effect of incarceration on sexual networks and sexual partnership exchange among BSMM/BTW. We estimate the influence of incarceration on selling sex and mediating pathways among 1169 BSMM/BTW enrolled in the HIV Prevention Trials Network (HPTN) 061 cohort to assess this relationship. Mediators investigated were social support, violence, illicit drug use, and distress due to experienced racism and homophobia. During the 6 months following baseline, 14% of the cohort was incarcerated, including 24% of BTW. After adjustment, recent incarceration was associated with 1.57 (95% CI 1.02, 2.42) times the risk of subsequently selling sex. The hypothesized mediators together explained 25% of the relationship, with an indirect effect risk ratio of 1.09 (95% CI 0.97, 1.24). Our results document an association and call for more research investigating mechanisms.

BACKGROUND:Recent studies have demonstrated considerable interindividual variability in postprandial glucose response (PPGR) to the same foods, suggesting the need for more precise methods for predicting and controlling PPGR. In the Personal Nutrition Project, the investigators tested a precision nutrition algorithm for predicting an individual's PPGR. OBJECTIVE:This study aimed to compare changes in glycemic variability (GV) and HbA1c in 2 calorie-restricted weight loss diets in adults with prediabetes or moderately controlled type 2 diabetes (T2D), which were tertiary outcomes of the Personal Diet Study. METHODS:The Personal Diet Study was a randomized clinical trial to compare a 1-size-fits-all low-fat diet (hereafter, standardized) with a personalized diet (hereafter, personalized). Both groups received behavioral weight loss counseling and were instructed to self-monitor diets using a smartphone application. The personalized arm received personalized feedback through the application to reduce their PPGR. Continuous glucose monitoring (CGM) data were collected at baseline, 3 mo and 6 mo. Changes in mean amplitude of glycemic excursions (MAGEs) and HbA1c at 6 mo were assessed. We performed an intention-to-treat analysis using linear mixed regressions. RESULTS:We included 156 participants [66.5% women, 55.7% White, 24.1% Black, mean age 59.1 y (standard deviation (SD) = 10.7 y)] in these analyses (standardized = 75, personalized = 81). MAGE decreased by 0.83 mg/dL per month for standardized (95% CI: 0.21, 1.46 mg/dL; P = 0.009) and 0.79 mg/dL per month for personalized (95% CI: 0.19, 1.39 mg/dL; P = 0.010) diet, with no between-group differences (P = 0.92). Trends were similar for HbA1c values. CONCLUSIONS:Personalized diet did not result in an increased reduction in GV or HbA1c in patients with prediabetes and moderately controlled T2D, compared with a standardized diet. Additional subgroup analyses may help to identify patients who are more likely to benefit from this personalized intervention. This trial was registered at clinicaltrials.gov as NCT03336411.

INTRODUCTION:Beverage taxes are associated with declines in sugar-sweetened beverage sales and consumption, but few studies have evaluated the associations of these taxes with health outcomes. This study analyzed changes in dental decay after the implementation of the Philadelphia sweetened beverage tax. METHODS:Electronic dental record data were obtained on 83,260 patients living in Philadelphia and control areas from 2014 to 2019. Difference-in-differences analyses compared the number of new Decayed, Missing, and Filled Teeth with that of new Decayed, Missing, and Filled Surfaces before (January 2014-December 2016) and after (January 2019-December 2019) tax implementation in Philadelphia and control patients. Analyses were conducted in older children/adults (aged ≥15 years) and younger children (aged <15 years). Subgroup analyses stratified by Medicaid status. Analyses were conducted in 2022. RESULTS:The number of new Decayed, Missing, and Filled Teeth did not change after tax implementation in Philadelphia in panel analyses of older children/adults (difference-in-differences= -0.02, 95% CI= -0.08, 0.03) or younger children (difference-in-differences=0.07, 95% CI= -0.08, 0.23). There were similarly no post-tax changes in the number of new Decayed, Missing, and Filled Surfaces. However, in cross-sectional samples of patients on Medicaid, the number of new Decayed, Missing, and Filled Teeth was lower after tax implementation in older children/adults (difference-in-differences= -0.18, 95% CI= -0.34, -0.03; -22% decline) and younger children (difference-in-differences= -0.22, 95% CI= -0.46, 0.01; -30% decline), with similar results for number of new Decayed, Missing, and Filled Surfaces. CONCLUSIONS:The Philadelphia beverage tax was not associated with reduced tooth decay in the general population, but it was associated with reduced tooth decay in adults and children on Medicaid, suggesting potential health benefits for low-income populations.

HIV stigma remains a barrier in achieving optimal HIV treatment. We studied the prevalence and predictors of HIV stigma among adolescents and youth with HIV (AYWHIV) ages 15-24 years in Western Kenya. Of 1011 AYWHIV, 69% were female with a median age of 18 years. Most (59%) attended adolescent clinic days, and 40% attended support groups. One-quarter (27%) had experienced physical, 18% emotional, and 7% sexual violence. The majority of AYWHIV (88%) reported disclosure concerns, 48% reported perceived community stigma, 36% experienced, and 24% internalized stigma. Compared to AYWHIV attending adolescent clinics, those in general/adult clinics had higher internalized stigma. Similarly, having dropped out of school was associated with higher internalized stigma. AYWHIV in sexual relationships had higher experienced stigma and disclosure concerns. Lastly, exposure to violence was associated with higher experienced, internalized, perceived community stigma and disclosure concerns. These risk factors can be targeted when developing stigma-prevention interventions.