Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV.

Importance: Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women. Objective: To determine whether baseline or 1-year changes in plasma amyloid-ß40 (Aß40), Aß42, ratio of Aß42 to Aß40, total tau (t-tau), phosphorylated tau 231 (p-tau231), glial fibrillary acidic protein (GFAP), and/or neurofilament light chain (NFL) are associated with neuropsychological performance (NP) among women living with HIV (WLWH) and women living without HIV (WLWOH). Design, Setting, and Participants: This longitudinal, prospective, cohort study with 1-year repeated clinical measures (NP only measured once) and biospecimen collection occurred between 2017 and 2019. Participants were women aged 40 years or older from 10 clinical research sites in cities across the US that were part of the Women's Interagency HIV Study. Data analysis was conducted from April to December 2022. Exposure: Laboratory-confirmed HIV status and AD biomarkers. Main Outcomes and Measures: Sociodemographically adjusted NP T-scores (attention and working memory, executive function, processing speed, memory, learning, verbal fluency, motor function, and global performance) were the primary outcomes. Baseline and 1-year fasting plasma Aß40, Aß42, t-tau, p-tau231, GFAP, and NFL levels were measured and analyzed using multivariable linear regression. Results: The study consisted of 307 participants (294 aged ≥50 years [96%]; 164 African American or Black women [53%]; 214 women with a high school education or higher [70%]; 238 women who were current or former smokers [78%]; and 236 women [77%] who were overweight or obese [body mass index >25]) including 209 WLWH and 98 WLWOH. Compared with WLWOH at baseline, WLWH performed worse on learning (mean [SD] T-score 47.8 [11.3] vs 51.4 [10.5]), memory (mean [SD] T-score 48.3 [11.6] vs 52.4 [10.2]), verbal fluency (mean [SD] T-score 48.3 [9.8] vs 50.7 [8.5]), and global (mean [SD] T-score 49.2 [6.8] vs 51.1 [5.9]) NP assessments. Baseline median Aß40, GFAP, and NFL levels were higher among WLWH vs WLWOH. There were no differences in 1-year biomarker change by HIV serostatus. Lower learning, memory, and motor NP were associated with 1-year Aß40 increase; lower learning and motor with Aß42 increase; lower motor with p-tau231 increase; and lower processing speed, verbal fluency and motor with NFL increase in the entire sample. Among WLWH, a 1-year increase in Aß40 from baseline to follow-up was associated with worse learning, memory, and global NP; a 1-year increase in t-tau with worse executive function; and a 1-year increase in NFL with worse processing speed. Among WLWOH, a 1-year increase in Aß40 and Aß42 were associated with poorer memory performance and NFL was associated with poorer motor performance. Conclusions and Relevance: These findings suggest that increases in certain plasma AD biomarkers are associated with NP in WLWH and WLWOH and may be associated with later onset of AD, and measuring these biomarkers could be a pivotal advancement in monitoring aging brain health and development of AD among women with and without HIV.

Targeting Microglial Polarization to Improve TBI Outcomes.

Traumatic Brain Injury (TBI) is still the worldwide leading cause of mortality and morbidity in young adults. Improved safety measures and advances in critical care have increased chances of surviving a TBI, however, numerous secondary mechanisms contribute to the injury in the weeks and months that follow TBI. The past 4 decades of research have addressed many of the metabolic impairments sufficient to mitigate mortality, however, an enduring secondary mechanism, i.e. neuroinflammation, has been intractable to current therapy. Neuroinflammation is particularly difficult to target with pharmacological agents due to lack of specificity, the blood brain barrier, and an incomplete understanding of the protective and pathologic influences of inflammation in TBI. Recent insights into TBI pathophysiology have established microglial activation as a hallmark of all types of TBI. The inflammatory response to injury is necessary and beneficial while the death of activated microglial is not. This review presents new insights on the therapeutic and maladaptive features of the immune response after TBI with an emphasis on microglial polarization, followed by a discussion of potential targets for pharmacologic and non-pharmacologic treatments. In aggregate, this review presents a rationale for guiding TBI inflammation towards neural repair and regeneration rather than secondary injury and degeneration, which we posit could improve outcomes and reduce lifelong disease burden in TBI survivors.

The Current State of Neurosurgery in Haiti.

BACKGROUND: Even though surgical conditions account for as much as 32% of the global burden of disease, 5 billion people worldwide do not have access to timely, affordable surgical and anesthetic care. Access to surgical care is separated along socioeconomic divides, and these disparities are most pronounced in low-and middle-income countries, such as the Caribbean nation of Haiti, where the availability of specialty surgical services like neurosurgery are scant, or completely absent. METHODS: This paper provides a narrative account of current neurosurgery-related activity in Haiti, a nation whose social, political, and economic context is unique in the Americas. RESULTS: After some background information and a bibliometric analysis of recent research efforts, we provide brief biographical sketches of Haiti's local neurosurgical leaders and an overview of recent initiatives in Haitian neurosurgical capacity building. CONCLUSIONS: The paper concludes with recommendations to guide the international neurosurgery community in future contributions.