Effects of Candesartan vs Lisinopril on Neurocognitive Function in Older Adults With Executive Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Observational studies have suggested that angiotensin receptor blockers are associated with a unique cognitive protection. It is unclear if this is due to reduced blood pressure (BP) or angiotensin receptors type 1 blockade. Objective: To determine neurocognitive effects of candesartan vs lisinopril in older adults with mild cognitive impairment (MCI). Design, Setting, and Participants: This randomized clinical trial included participants aged 55 years or older with MCI and hypertension. Individuals were withdrawn from prior antihypertensive therapy and randomized in a 1 to 1 ratio to candesartan or lisinopril from June 2014 to December 2018. Participants underwent cognitive assessments at baseline and at 6 and 12 months. Brain magnetic resonance images were obtained at baseline and 12 months. This intent-to-treat study was double-blind and powered for a sample size accounting for 20% dropout. Data were analyzed from May to October 2019. Interventions: Escalating doses of oral candesartan (up to 32 mg) or lisinopril (up to 40 mg) once daily. Open-label antihypertensive drug treatments were added as needed to achieve BP less than 140/90 mm Hg. Main Outcomes and Measures: The primary outcome was executive function (measured using the Trail Making Test, Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research tool) and secondary outcomes were episodic memory (measured using the Hopkins Verbal Learning Test-Revised) and microvascular brain injury reflected by magnetic resonance images of white matter lesions. Results: Among 176 randomized participants (mean [SD] age, 66.0 [7.8] years; 101 [57.4%] women; 113 [64.2%] African American), 87 were assigned to candesartan and 89 were assigned to lisinopril. Among these, 141 participants completed the trial, including 77 in the candesartan group and 64 in the lisinopril group. Although the lisinopril vs candesartan groups achieved similar BP (12-month mean [SD] systolic BP: 130 [17] mm Hg vs 134 [20] mm Hg; P = .20; 12-month mean [SD] diastolic BP: 77 [10] mm Hg vs 78 [11] mm Hg; P = .52), candesartan was superior to lisinopril on the primary outcome of executive function measured by Trail Making Test Part B (effect size [ES] = -12.8 [95% CI, -22.5 to -3.1]) but not Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research score (ES = -0.03 [95% CI, -0.08 to 0.03]). Candesartan was also superior to lisinopril on the secondary outcome of Hopkins Verbal Learning Test-Revised delayed recall (ES = 0.4 [95% CI, 0.02 to 0.8]) and retention (ES = 5.1 [95% CI, 0.7 to 9.5]). Conclusions and Relevance: These findings suggest that in older adults with MCI, 1-year treatment with candesartan had superior neurocognitive outcomes compared with lisinopril. These effects are likely independent of the BP-lowering effect of candesartan. Trial Registration: ClinicalTrials.gov Identifier: NCT01984164.

Perceived Stress is Associated with Alzheimer's Disease Cerebrospinal Fluid Biomarkers in African Americans with Mild Cognitive Impairment.

BACKGROUND: African Americans (AA) have a higher Alzheimer's disease (AD) prevalence and report more perceived stress than White Americans. The biological basis of the stress-AD link is unclear. This study investigates the connection between stress and AD biomarkers in a biracial cohort. OBJECTIVE: Establish biomarker evidence for the observed association between stress and AD, especially in AA. METHODS: A cross-sectional study (n = 364, 41.8% AA) administering cognitive tests and the perceived stress scale (PSS) questionnaire. A subset (n = 309) provided cerebrospinal fluid for measurement of Aß42, Tau, Ptau, Tau/Aß42 (TAR), and Ptau/Aß42 (PTAR). Multivariate linear regression, including factors that confound racial differences in AD, was performed. RESULTS: Higher PSS scores were associated with higher Ptau (ß= 0.43, p = 0.01) and PTAR (ß= 0.005, p = 0.03) in AA with impaired cognition (mild cognitive impairment). CONCLUSION: Higher PSS scores were associated with Tau-related AD biomarker indices in AA/MCI, suggesting a potential biological connection for stress with AD and its racial disparity.

Respiratory Syncytial Virus-Associated Hospitalizations Among Young Children: 2015-2016.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalized acute respiratory illness (ARI) among young children. With RSV vaccines and immunoprophylaxis agents in clinical development, we sought to update estimates of US pediatric RSV hospitalization burden. METHODS: Children <5 years old hospitalized for ARI were enrolled through active, prospective, population-based surveillance from November 1, 2015, to June 30, 2016, at 7 US pediatric hospital sites. Clinical information was obtained from parent interviews and medical records. Midturbinate nasal and throat flocked swabs were collected and tested for RSV by using molecular diagnostic assays at each site. We conducted descriptive analyses and calculated population-based rates of RSV-associated hospitalizations. RESULTS: Among 2969 hospitalized children included in analyses, 1043 (35%) tested RSV-positive; 903 (87%) children who were RSV-positive were <2 years old, and 526 (50%) were <6 months old. RSV-associated hospitalization rates were 2.9 per 1000 children <5 years old and 14.7 per 1000 children <6 months old; the highest age-specific rate was observed in 1-month-old infants (25.1 per 1000). Most children who were infected with RSV (67%) had no underlying comorbid conditions and no history of preterm birth. CONCLUSIONS: During the 2015-2016 season, RSV infection was associated with one-third of ARI hospitalizations in our study population of young children. Hospitalization rates were highest in infants <6 months. Most children who were RSV-positive had no history of prematurity or underlying medical conditions, suggesting that all young children could benefit from targeted interventions against RSV.

Racial Disparity in Cerebrospinal Fluid Amyloid and Tau Biomarkers and Associated Cutoffs for Mild Cognitive Impairment.

Importance: Prior evidence suggests that racial differences exist in tau biomarkers in mild cognitive impairment (MCI) and Alzheimer disease (AD). Whether this reported disparity is associated with a differential level of neurodegeneration and disease stage or with underlying mechanisms separate from amyloid or tau is unclear. Objectives: To compare cerebrospinal fluid (CSF) biomarkers in African American and white individuals with normal cognition and MCI, to estimate race-based cutoffs for these biomarkers that maximize diagnostic discrimination between normal cognition and MCI, and to study the association of demographic characteristics, cognitive performance, and common vascular risk factors with these differences. Design, Setting, and Participants: This case-control study conducted from March 1, 2016, through January 31, 2019, included participants in the Brain Stress Hypertension and Aging Research Program cohort undergoing baseline assessment. Participants were 50 years or older and recruited from the Atlanta, Georgia, area. Exposures: Self-reported race and cognitive status categorized using modified Petersen criteria and clinical consensus diagnosis. Main Outcomes and Measures: Levels of ß-amyloid 1-42 (Aß1-42), tau, and phosphorylated tau 181 (pTau181), the ratio of tau or pTau181 to Aß1-42, and hippocampal volume on magnetic resonance imaging of the brain. Results: Data from 362 study participants were analyzed (mean [SD] age, 65.6 [7.9] years), of whom 152 (42.0%) were African American, 230 (63.5%) were women, and 189 (52.2%) had MCI. After adjustment for demographic characteristics and cognitive performance, lower mean (SE) levels were observed in African American vs white individuals with MCI for tau (52.40 [5.90] vs 78.98 [5.02] pg/mL; P = .001) and pTau181 (15.42 [2.06] vs 25.24 [1.75] pg/mL; P = .001) and a lower pTau181 to Aß1-42 ratio (0.07 [0.02] vs 0.14 [0.01]; P = .003). There were no racial differences in the normal cognition group or in hippocampal volumes in the MCI group. Cutoffs for CSF biomarkers were higher for Aß1-42 in African American relative to white individuals (208 [95% CI, 126-321] vs 197 [95% CI, 183-245] pg/mL) and lower for tau (51 [95% CI, 31-59] vs 59 [95% CI, 56-92] pg/mL) and pTau181 (12 [95% CI, 12-19] vs 20 [95% CI, 12-27] pg/mL) levels. Cutoffs for the pTau181 to Aß1-42 ratio were 0.05 (95% CI, 0.03-0.12) for African American participants and 0.05 (95% CI, 0.05-0.13) for white participants. Conclusions and Relevance: This study found that African American individuals had lower levels of tau-based biomarkers that were not likely explained by the degree of disease stage or neurodegeneration reflected by hippocampal volumes. This study suggests that race is an important factor when interpreting CSF biomarkers, especially in the clinical diagnosis of prodromal AD. It appears that using the pTau181 to Aß1-42 ratio may ameliorate these differences.

The Impacts of Residential Location on the Risk of HIV Virologic Failure Among ART Users in Durban, South Africa.

Using a case-control study of patients receiving antiretroviral treatment (ART) in 2010-2012 at McCord Hospital in Durban, South Africa, we sought to understand how residential locations impact patients' risk of virologic failure (VF). Using generalized estimating equations to fit logistic regression models, we estimated the associations of VF with socioeconomic status (SES) and geographic access to care. We then determined whether neighborhood-level poverty modifies the association between individual-level SES and VF. Automobile ownership for men and having non-spouse family members pay medical care for women remained independently associated with increased odds of VF for patients dwelling in moderately and severely poor neighborhoods. Closer geographic proximity to medical care was positively associated with VF among men, while higher neighborhood-level poverty was positively associated with VF among women. The programmatic implications of our findings include developing ART adherence interventions that address the role of gender in both the socioeconomic and geographical contexts.

Prevalence of Human Papillomavirus Among Females After Vaccine Introduction-National Health and Nutrition Examination Survey, United States, 2003-2014.

Background: Human papillomavirus (HPV) vaccine was recommended in 2006 for routine vaccination of US females aged 11-12 years. Most vaccine used through 2014 was quadrivalent vaccine (4vHPV), which prevents HPV-6, -11, -16, and -18 infection. To evaluate vaccine impact, we measured HPV prevalence in the National Health and Nutrition Examination Survey (NHANES). Methods: We analyzed HPV DNA types detected in self-collected cervicovaginal specimens and demographic, sexual behavior, and self-reported vaccination data from females 14-34 years old. We estimated HPV prevalence in the prevaccine (2003-2006) and vaccine eras (2007-2010 and 2011-2014). Results: Among 14- to 19-year-olds, 4vHPV-type prevalence decreased from 11.5% (95% confidence interval [CI], 9.1%-14.4%) in 2003-2006 to 3.3% (95% CI, 1.9%-5.8%) in 2011-2014, when ≥1-dose coverage was 55%. Among 20- to 24-year-olds, prevalence decreased from 18.5% (95% CI, 14.9%-22.8%) in 2003-2006 to 7.2% (95% CI, 4.7%-11.1%) in 2011-2014, when ≥1-dose coverage was 43%. Compared to 2003-2006, 4vHPV prevalence in sexually active 14- to 24-year-olds in 2011-2014 decreased 89% among those vaccinated and 34% among those unvaccinated. Vaccine effectiveness was 83%. Conclusions: Within 8 years of vaccine introduction, 4vHPV-type prevalence decreased 71% among 14- to 19-year-olds and 61% among 20- to 24-year-olds. Estimated vaccine effectiveness was high. The decrease in 4vHPV-type prevalence among unvaccinated females suggests herd protection.

Novel Predictors of Poor Retention Following a Down-Referral from a Hospital-Based Antiretroviral Therapy Program in South Africa.

Worldwide, HIV care is becoming increasingly decentralized. For patients in care at centralized facilities, this requires down-referral to local clinics for their HIV care. Information on the real-world experience and predictors of retention in care at the time of down-referral is lacking. We sought to evaluate the effect of patient-level factors on retention in care surrounding a period of down-referral to new clinics for patients with and without virologic failure (VF) on their first-line ART. We conducted a secondary analysis of a case-control study of people living with HIV attending the Sinikethemba (SKT) Clinic at McCord Hospital in Durban, South Africa. Cases (VF) and controls (no VF) responded to a questionnaire focused on individual-level factors. Subsequently, participants self-reported either changing service provider (retained in care), were unable to be reached, died or reported not attending a new provider visit (not retained in care). Multivariate logistic regression was conducted with factors associated with not being retained in care in a univariate analysis. In all, 458 patients were enrolled in the parent study (158 cases and 300 controls) with a median age of 38 years old and with 65% women. A total of 436 (95%) participants successfully established care at the down-referral clinic. In the multivariate analysis, not being pleased with the clinic (SKT), lower adherence scores, and shorter duration of ART predicted failure of down-referral. Down-referral was successful even for patients with VF. Individual-level factors could act as predictors for patients at increased risk for poor retention during the down-referral process to a local clinic.