Lower in vivo locus coeruleus integrity is associated with lower cortical thickness in older individuals with elevated Alzheimer's pathology: a cohort study.

BACKGROUND: Autopsy work indicates that the widely-projecting noradrenergic pontine locus coeruleus (LC) is among the earliest regions to accumulate hyperphosphorylated tau, a neuropathological Alzheimer's disease (AD) hallmark. This early tau deposition is accompanied by a reduced density of LC projections and a reduction of norepinephrine's neuroprotective effects, potentially compromising the neuronal integrity of LC's cortical targets. Previous studies suggest that lower magnetic resonance imaging (MRI)-derived LC integrity may signal cortical tissue degeneration in cognitively healthy, older individuals. However, whether these observations are driven by underlying AD pathology remains unknown. To that end, we examined potential effect modifications by cortical beta-amyloid and tau pathology on the association between in vivo LC integrity, as quantified by LC MRI signal intensity, and cortical neurodegeneration, as indexed by cortical thickness. METHODS: A total of 165 older individuals (74.24 ± 9.72 years, ~ 60% female, 10% cognitively impaired) underwent whole-brain and dedicated LC 3T-MRI, Pittsburgh Compound-B (PiB, beta-amyloid) and Flortaucipir (FTP, tau) positron emission tomography. Linear regression analyses with bootstrapped standard errors (n = 2000) assessed associations between bilateral cortical thickness and i) LC MRI signal intensity and, ii) LC MRI signal intensity interacted with cortical FTP or PiB (i.e., EC FTP, IT FTP, neocortical PiB) in the entire sample and a low beta-amyloid subsample. RESULTS: Across the entire sample, we found a direct effect, where lower LC MRI signal intensity was associated with lower mediolateral temporal cortical thickness. Evaluation of potential effect modifications by FTP or PiB revealed that lower LC MRI signal intensity was related to lower cortical thickness, particularly in individuals with elevated (EC, IT) FTP or (neocortical) PiB. The latter result was present starting from subthreshold PiB values. In low PiB individuals, lower LC MRI signal intensity was related to lower EC cortical thickness in the context of elevated EC FTP. CONCLUSIONS: Our findings suggest that LC-related cortical neurodegeneration patterns in older individuals correspond to regions representing early Braak stages and may reflect a combination of LC projection density loss and emergence of cortical AD pathology. This provides a novel understanding that LC-related cortical neurodegeneration may signal downstream consequences of AD-related pathology, rather than being exclusively a result of aging.

The relationship between state-level structural racism and disparities between the non-hispanic black and non-hispanic white populations in multiple health outcomes.

AIMS: While several studies have examined the impact of individual indicators of structural racism on single health outcomes, few have explicitly modeled racial disparities in a wide range of health outcomes using a multidimensional, composite structural racism index. This paper builds on the previous research by examining the relationship between state-level structural racism and a wider array of health outcomes, focusing on racial disparities in mortality from firearm homicide, infant mortality, stroke, diabetes, hypertension, asthma, HIV, obesity, and kidney disease. METHODS: We used a previously developed state structural racism index that consists of a composite score derived by averaging eight indicators across five domains: (1) residential segregation; (2) incarceration; (3) employment; (4) economic status/wealth; and (5) education. Indicators were obtained for each of the 50 states using Census data from 2020. We estimated the Black-White disparity in each health outcome in each state by dividing the age-adjusted mortality rate for the non-Hispanic Black population by the age-adjusted mortality rate for the non-Hispanic White population. These rates were obtained from the CDC WONDER Multiple Cause of Death database for the combined years 1999-2020. We conducted linear regression analyses to examine the relationship between the state structural racism index and the Black-White disparity in each health outcome across the states. In multiple regression analyses, we controlled for a wide range of potential confounding variables. RESULTS: Our calculations revealed striking geographic differences in the magnitude of structural racism, with the highest values generally being observed in the Midwest and Northeast. Higher levels of structural racism were significantly associated with greater racial disparities in mortality for all but two of the health outcomes. CONCLUSIONS: There is a robust relationship between structural racism and Black-White disparities in multiple health outcomes across states. Programs and policies to reduce racial heath disparities must include strategies to help dismantle structural racism and its consequences.

Gamblers' Perception of the Playscan Risk Assessment: A Mixed-Methods Study.

Responsible gambling (RG) tools are globally widespread; they aim to prevent or decrease the harm caused by gambling. However, existing research suggests that several included features do not decrease gambling or significantly reduce the subsequent harm. Most of the previous studies have used gambling data to understand the changes in gambling behavior. However, the literature lacks research regarding gamblers' experience and perception of RG tools, which may provide insight into increasing the usage and effectiveness of RG tools. This mixed-methods study aimed to explore gamblers' perception of their risk assessment in the RG tool Playscan regarding developing harmful gambling problems. Overall, 757 participants rated the perceived accuracy of their risk assessment and their perception of the overall RG tool that conducted the assessment. Participants were also allowed to leave a comment providing feedback, which was analyzed using thematic analysis. Quantitative data was analyzed using logistic regression and structural equation modeling. Qualitative analyses revealed that most of the participants were pleased with the risk assessment and found it helpful. Moderated mediation analysis showed that participants' assessment agreement partially mediated the association between expressing a negative view and their general view of Playscan. These results highlight the need to decrease the level of disagreement for promoting a better general view of RG tools to potentially increase their usage and effectiveness.