Objective Compared to older Caucasians, older African Americans have higher risks of developing Alzheimer’s disease (AD), and lower cerebrospinal fluid (CSF) tau biomarker levels. It is not known whether tau-related differences begin earlier in life, and whether race modifies other AD-related biomarkers such as inflammatory proteins. Methods We performed multiplex cytokine analysis in a healthy middle-aged cohort with family history of AD (n=68) and an older cohort (n=125) with normal cognition (NC), mild cognitive impairment (MCI), or AD dementia. After identifying baseline IL-9 level and AD-associated IL-9 change to differ according to race, we performed immunohistochemical analysis for proteins mechanistically linked to IL-9 in brains of African Americans and Caucasians (n=38), and analyzed post-mortem IL-9-related gene expression profiles in the publically available Mount Sinai cohort (26 African Americans and 180 Caucasians). Results Compared to Caucasians with NC, African Americans with NC had lower CSF tau, p-Tau181, and IL-9 levels in both living cohorts. Conversely, AD was only correlated with increased CSF IL-9 levels in African Americans but not Caucasians. Immunohistochemical analysis revealed peri-vascular, neuronal, and glial cells immunoreactive to IL-9, and quantitative analysis in two independent US cohorts showed AD to correlate with molecular changes (upstream differentiation marker and downstream effector cell marker) of IL-9 upregulation only in African Americans but not Caucasians. Interpretation Baseline and AD-associated IL-9 differences between African Americans and Caucasians point to distinct molecular phenotypes for AD according to ancestry. Genetic and non-genetic factors need to be considered in future AD research involving unique populations.

Background: The rate of AD for AAs is 64% higher than for non-Hispanic White Americans (Whites). It is hypothesized that poor peripheral vascular function, in combination with genetics, stress and inflammation may directly contribute to the accumulation of AD pathologic biomarkers. These risk factors may disproportionately affect AAs. Objective: Our objective was to determine if in a healthy middle-aged cohort at risk for AD (1) AD biomarkers in CSF differ by race, (2) peripheral vascular dysfunction and cognition are related to a higher burden of CSF AD biomarkers, and (3) these relationships differ by race. Methods: We enrolled 82 cognitively normal, middle-aged (45 and older) adults including AAs and Whites at high risk for AD due to parental history. Study procedures included lumbar puncture, vascular ultrasound and cognitive testing. Results: While participants were in overall good health, AAs exhibited poorer indices of preclinical vascular health, including higher central SBP, central MAP, and EndoPAT AI, a marker of arterial stiffness. AAs also had significantly less CSF tau burden than Whites. After polynomial regression analysis, adjusted for age, gender, education, and ApoE4 status, race significantly modified the relationship between total tau, phospho-tau and Trails b, a marker of executive function. Small differences in tau correlated with poorer cognition in AAs. Conclusion: In a healthy middle-aged cohort at risk for AD, AAs had worse peripheral vascular health and worse cognition than Whites. Despite lower tau burden overall, race modified the relationship between tau and cognition, such that small differences in tau between AAs was related to worse cognition when compared to Whites.

Research indicates that certain antihypertensive medications alter Alzheimer's disease (AD) biomarkers in Caucasians. The renin angiotensin system (RAS) regulates blood pressure (BP) in the body and the brain and may directly influence AD biomarkers, including amyloid-β (Aβ) neuropathology, cerebral blood flow (CBF), and inflammatory markers. This hypothesis is supported by studies, including ours, showing that antihypertensives targeting the RAS reduce the risk and slow the progression of AD in Caucasians. While mounting evidence supports a protective role of RAS medications in Caucasians, this mechanism has not been explored in African Americans. To assess the mechanism by which RAS medications modify the brain RAS, cerebrospinal fluid (CSF) Aβ, CBF, and inflammatory markers in African Americans, we are conducting an eight month, Phase Ib randomized, placebo controlled trial, enrolling 60 middle-aged (45-70 years), non-demented individuals, at risk for AD by virtue of a parental history. Participants include normotensive and treated hypertensives that have never been exposed to a RAS medication. Participants are randomized (1 : 1:1) by gender and BP medication use (yes/no) to one of three groups: placebo, or 20 mg, or 40 mg telmisartan (Micardis), to determine the dose required to penetrate the CNS. Our overarching hypothesis is that, compared to placebo, both doses of telmisartan will penetrate the CNS and produce salutary, dose dependent effects on the brain RAS as well as CSF Aβ, CBF, and CSF inflammatory markers in African Americans, over eight months. This manuscript describes the trial rationale and design.

Purpose Symptoms of depression and anxiety in pregnancy have been linked to later impaired caregiving. However, mood symptoms are often elevated in pregnancy and may reflect motherhood-specific concerns. In contrast, little is known about the effects of pre-pregnancy depression and anxiety on postpartum caregiving. Understanding these developmental risk factors is especially important when childbearing also occurs during adolescence. Methods The sample comprised 188 adolescent mothers (ages 12–19 years) who had participated in a longitudinal study since childhood. Mothers were observed in face-to-face interaction with the infant at 4 months postpartum, and caregiving behaviors (sensitivity, hostile-intrusive behavior and mental state talk) were coded independently. Data on self-reported depression and anxiety gathered in the five years prior to childbirth were drawn from the large-scale longitudinal study. Results Parallel process latent growth curve models revealed unique effects of distal anxiety and slow decline in anxiety over time on lower levels of maternal mental state talk after accounting for the overlap with depression symptom development. Depressive symptoms showed significant stability from distal measurement to the postpartum period, but only concurrent postpartum mood was associated with poorer quality of maternal speech. Conclusions The results highlight specific targets for well-timed preventive interventions with vulnerable dyads.

Background: African Americans (AA) are more likely to develop Alzheimer’s disease (AD) than Caucasians (CC). Dietary modification may have the potential to reduce the risk of developing AD. Objective: The objective of this study is to investigate the relationship between Southern and Prudent diet patterns and cognitive performance in individuals at risk for developing AD. Design: Cross-sectional observational study. Participants: Sixty-six cognitively normal AA and CC individuals aged 46-77 years with a parental history of AD were enrolled. Measurements: Participants completed a Food Frequency questionnaire, cognitive function testing, which consisted of 8 neuropsychological tests, and cardiovascular risk factor assessments, including evaluation of microvascular and macrovascular function and ambulatory blood pressure monitoring. Results: Results revealed a relationship between the Southern diet and worse cognitive performance among AAs. AAs who consumed pies, mashed potatoes, tea, and sugar drinks showed worse cognitive performance (p<0.05) compared with CCs. In addition, gravy (p=0.06) and cooking oil/fat (p=0.06) showed negative trends with cognitive performance in AAs. In both CC and AA adults, greater adherence to a Prudent dietary pattern was associated with better cognitive outcomes. Cardiovascular results show that participants are overall healthy. AAs and CCs did not differ on any vascular measure including BP, arterial stiffness and endothelial function. Conclusion: Research shows that dietary factors can associate with cognitive outcomes. This preliminary cross-sectional study suggests that foods characteristic of the Southern and Prudent diets may have differential effects on cognitive function in middle-aged individuals at high risk for AD. Results suggest that diet could be a non-pharmaceutical tool to reduce cognitive decline in racially diverse populations. It is possible that the increased prevalence of AD in AA could be partially reduced via diet modification.