Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants.

INTRODUCTION: We estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle-aged and older adults. METHODS: Among 45,616 dementia-free participants aged 45-80, linear regressions tested whether genetic risk score for AD (AD-GRS) had age-dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume. RESULTS: AD-GRS modified the estimated effect of age (per decade) on the amygdala (-0.41 mm3 [-0.42, -0.40]); hippocampus (-0.45 mm3 [-0.45, -0.44]), nucleus accumbens (-0.55 mm3 [-0.56, -0.54]), thalamus (-0.38 mm3 [-0.39, -0.37]), and medial orbitofrontal cortex (-0.23 mm3 [-0.24, -0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD-GRS excluding apolipoprotein E (APOE) was additionally associated with entorhinal and middle temporal cortices. DISCUSSION: APOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.

Associations of Everyday and Lifetime Experiences of Discrimination With Willingness to Undergo Alzheimer Disease Predictive Testing.

BACKGROUND AND OBJECTIVES: Rapid developments in Alzheimer disease (AD) biomarker research suggest that predictive testing may become widely available. To ensure equal access to AD predictive testing, it is important to understand factors that affect testing interest. Discrimination may influence attitudes toward AD testing, particularly among racially and ethnically minoritized populations, because of structural racism in health care systems. This study examined whether everyday or lifetime discrimination experiences shape interest in AD predictive testing. METHODS: In the 2010 and 2012 biennial Health and Retirement Study waves, respondents were randomly selected to complete questions on interest in receiving free testing that could determine whether they would develop AD in the future. The exposures were everyday discrimination (6 items) and lifetime discrimination (7 items); both were transformed into a binary variable. Logistic regression models predicting interest in AD testing were controlled for deciles of propensity scores for each discrimination measure. Odds ratios were re-expressed as risk differences (RDs). RESULTS: Our analytic sample included 1,499 respondents. The mean age was 67 (SD = 10.2) years, 57.4% were women, 65.7% were White, and 80% endorsed interest in AD predictive testing. Most of the participants (54.7%) experienced everyday discrimination in at least one domain; 24.1% experienced major lifetime discrimination in at least one domain. Those interested in predictive testing were younger (66 vs 70 years) and more likely to be Black (20% vs 15%) or Latinx (14% vs 8%) than participants uninterested in testing. The probability of wanting an AD test was not associated with discrimination for Black (RD everyday discrimination = -0.026; 95% CI [-0.081 to 0.029]; RD lifetime discrimination = -0.012; 95% CI [-0.085 to 0.063]) or Latinx (RD everyday discrimination = -0.023, 95% CI [-0.082 to 0.039]; RD lifetime discrimination = -0.011; 95% CI [-0.087 to 0.064]) participants. DISCUSSION: Despite historical and contemporary experiences of discrimination, Black and Latinx individuals express interest in AD testing. However, Black and Latinx individuals remain underrepresented in AD research, including research on AD testing. Interest in personalized information about dementia risk may be a pathway to enhance their inclusion in research and clinical trials.

Association of systemic inflammation with posttraumatic stress disorder after a myocardial infarction.

Background: Adverse mental health conditions including depression, posttraumatic stress disorder (PTSD), and anxiety are prevalent among patients who survive myocardial infarctions (MI) and are associated with adverse outcomes. The mechanisms underlying these associations, however, are not well understood. Inflammatory pathways may mediate the cardiovascular outcomes of patients with mental health disorders. We examined the bidirectional association between PTSD symptoms and inflammatory biomarkers in a young/middle-aged post MI population. We further examined how this association may differ between women and men as well as between Black and non-Black individuals. Methods: Participants included individuals with early onset MI between the ages 25 and 60. Mental health scores for depression, PTSD, perceived stress, and anxiety as well as inflammatory biomarkers, interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), were collected at baseline and at six-month follow up. We examined the bidirectional changes in mental health symptoms and inflammatory biomarkers between baseline and follow-up. Results: Among 244 patients in the study (mean age: 50.8, 48.4% female, 64.3% Black), the geometric means for IL-6 level and hsCRP at rest were 1.7 pg/mL and 2.76 mg/L, respectively. Mental health scores at baseline did not consistently predict changes in inflammatory biomarkers at follow-up. However, baseline levels of both IL-6 and hsCRP were robustly associated with an increase in re-experiencing PTSD symptoms at 6 months: in adjusted linear mixed models, there was a 1.58-point increase in re-experiencing PTSD symptoms per unit of baseline hsCRP (p = 0.01) and 2.59-point increase per unit of baseline IL-6 (p = 0.02). Once the analysis was stratified by race, the association was only noted in Black individuals. Baseline inflammation was not associated with change in any of the other mental health symptom scores. Conclusion: Markers of inflammation are associated with an increase in post-event PTSD symptoms in younger or middle-aged patients who experienced an MI, especially Black patients. These results suggest a mechanistic link between inflammation and the development of PTSD among individuals with cardiovascular disease.