Global Brain Health Institute

The 4th UN General Assembly declaration on non-communicable diseases (NCDs) and mental health, adopted on Dec 15, 2025, was notable for its explicit inclusion of dementia, bringing dementia prevention into focus as an international public policy priority.1 A central question therefore becomes how dementia prevention will be prioritised, resourced, and implemented and how it will be integrated into existing NCD policies and health-system strategies (appendix).

BackgroundDespite the availability of effective vaccines, flu and COVID-19 uptake remains suboptimal, including among Indigenous communities in California who face unique barriers to accessing public health information. While previous research has evaluated health communication message content and design, fewer studies have systematically compared different dissemination strategies for the same intervention, leaving gaps in understanding optimal approaches for reaching marginalized populations.ObjectiveThis protocol describes a three-arm dissemination study designed to compare the effectiveness of different strategies for distributing COVID-19 and flu vaccine promotion videos among Indigenous Peoples residing in California, including American Indian and Alaska Natives, and migrant Indigenous Peoples from Latin America.MethodsFollowing extensive formative work, including cross-sectional surveys, social network analyses, a discrete choice experiment, and qualitative focus groups conducted with guidance from an Indigenous Community Advisory Board, we developed four 30-second vaccine promotion videos available in English and Spanish, two targeting American Indian and Alaska Native communities and 2 targeting Latin American communities. Videos will be translated to four Indigenous languages (Purépecha, Mam, Zapoteco, and Mixteco). The study compared three dissemination strategies implemented over a two-month period: (1) targeted social media advertisements on Facebook and Instagram, (2) distribution through community-based organizations using their established communication channels, and (3) peer-to-peer sharing through Indigenous community members (“seeds”) recruited from previous research. Primary outcomes focus on dissemination effectiveness, defined by measures of reach (eg, link shares, clicks and video views), engagement (eg, watch time and survey completion), and message impact (eg, trust in the message and vaccination intent), assessed using Bitly link tracking, YouTube analytics, and follow-up surveys. Descriptive and comparative analyses will be conducted to assess differences across dissemination strategies.ResultsThe study was funded in January 2023. Intervention development was completed in July 2025. Dissemination activities and data collection across all three study arms were conducted between October 6, 2025, to November 28, 2025, aligned with the COVID-19 and influenza vaccination season in the United States. Data consolidation, cleaning, and analyses began January 2026 and primary results are expected to be submitted for publication in Spring 2026.ConclusionsThis study addresses a critical gap in health communication research by providing a systematic methodology for comparing digital dissemination strategies within Indigenous communities. The combination of community-informed recruitment, multilingual accessibility, and comprehensive digital tracking tools offers a replicable model for evaluating how public health messages spread through different channels, particularly for populations historically excluded from traditional outreach efforts.

Over 80% of tuberculosis cases in the United States are due to reactivation of untreated latent tuberculosis infection (LTBI), most of whom were foreign born. LTBI treatment can greatly lower the risk of progression to active TB disease, and shorter treatment regimens increase the potential of migrants and other persons in vulnerable conditions, to complete treatment. We conducted across-sectional study to assess willingness to complete a one-month course of LTBI treatment among internal and international migrants living in Tijuana, BC, Mexico, and to identify factors associated with treatment unwillingness between November 2020 and April 2021. Prior to administering TB skin tests (TST), participants were asked if they would accept LTBI treatment if indicated by test results and clinical examination. Recruitment occurred in migrant shelters throughout Tijuana and at a storefront office conducting research and harm reduction services for people who use drugs. Among 595 participants, 80.4% were living in shelters, 3.5% were recruited at shelters but living independently, and 16.1% were recruited through the storefront office. Overall, 71 (11.9%) indicated that they were unwilling to take LTBI treatment and 109 (18.3%) had positive TST results. Unwillingness to take LTBI treatment was more common among participants from the storefront office compared to the shelter (64.6% vs. 1.8%, p<0.001). Since only 1.8% of shelter participants were unwilling to receive treatment, multivariable Poisson regression with robust variance estimation via GEE for identifying factors independently associated with LTBI treatment unwillingness was restricted to storefront participants. Treatment unwillingness among storefront participants was positively associated with perceiving health status as "good" or "very good" (prevalence ratio [PR]=2.37, 95% confidence interval [CI]: 1.52, 3.99) and heroin use in the past six months (PR=1.70; 95% CI: 1.33, 2.19). Unstable housing was reported as a barrier to treatment. These findings suggest that most migrants in Tijuana were willing to receive short-course LTBI treatment if indicated, yet willingness was lower among those at greatest risk of TB. Efforts to increase testing and treatment, as well as further research on overcoming barriers to treatment willingness are needed.

BackgroundWithdrawal of life-sustaining treatments (WLST) is a leading cause of death in patients with severe acquired brain injuries (ABI). These decisions often occur under conditions of prognostic uncertainty and time-critical therapeutic windows and may be shaped by a complex interplay of factors. Elucidating these influences is essential to ensure that WLST decisions are made in an informed, unbiased, and transparent manner, and in alignment with wishes of the patients as well as their surrogate decision makers.ObjectiveConduct a scoping review of literature to identify, elaborate and analyze the various factors that influence decisions to WLST in adult patients with ABI. This review aims to provide a comprehensive understanding of current practices.MethodsThis scoping review, conducted according to PRISMA-ScR guidelines, examined literature on WLST in adult ABI, in whom brain death had not been declared. The search was conducted in PubMed and Web of Science, up to August 2024. Studies were screened by title/abstract and full text, with data systematically extracted. Only original, peer-reviewed articles focusing on WLST in adult severe ABI patients were included. N = 2,963 independent papers were initially found, of which N = 2,881 were excluded. A final count of N = 81 independent papers were included.ResultsDemographic factors (age, sex, race, socioeconomic status, etc.; n = 50), prognosis and clinical factors (n = 59), family preferences (n = 28), physician-related factors and institutional context (n = 31), formal medical directive (n = 13), ethical/legal frameworks (n = 13), geographical differences (n = 9) and religious beliefs (n = 5) all played pivotal roles in WLST decisions. Older age consistently emerged as a determinant for WLST, as well as poor prognosis and white race.ConclusionWLST decisions are most often made for older adults, with age consistently identified as a key predictor, independent of the clinical severity of ABI. Additional factors such as race, socioeconomic status, advance directives, and variations in healthcare provider attitudes and institutional policies further contribute to disparities in WLST practices. Understanding these intersecting influences is essential to recognizing potential biases and promoting more equitable, patient-centered end-of-life decision-making.

While higher pyrazinamide and isoniazid exposures and slow NAT2 acetylator status were each associated with increased hepatotoxicity, only pyrazinamide exposure was associated when considering pharmacokinetic variables together. Rifampin exposure was not associated with hepatotoxicity, supporting further evaluation of doses up to 20 mg/kg/day in a larger trial.

ABSTRACT INTRODUCTION Alzheimer’s disease (AD) diagnostic guidelines emphasize subjective cognitive decline (SCD) preceding mild cognitive impairment (MCI), implicitly assuming awareness of cognitive decline (ACD) is preserved in preclinical AD. This study aimed to evaluate associations of decreased ACD with multimodal core AD biomarkers in cognitively unimpaired (CU) individuals. METHODS We analyzed data from CU individuals with baseline CSF biomarkers and 3-year longitudinal neuropsychological assessment (ALFA+ cohort). Decreased ACD was defined by concurrent decline in episodic memory and awareness using robust longitudinal references (Free and Cued Selective Reminding Test, Memory Binding Test, Wechsler Memory Scale, and Subjective Cognitive Decline Questionnaire). Biomarker outcomes included plasma and CSF p-tau181, p-tau181/Aβ42, p-tau217; Aβ ([¹⁸F]flutemetamol) and tau PET ([¹⁸F]RO948). Associations of ACD with AD biomarkers were evaluated using linear regression models. Sensitivity analyses were restricted to individuals with memory decline. RESULTS 350 CU individuals were included (mean age 61 years; 60% female; mean education 14 years; 35% CSF Aβ-positive). Episodic memory decline was identified in 61 (17%) individuals, of whom 25 (41%) also exhibited awareness decline; meeting criteria for decreased ACD. This group demonstrated greater levels of AD pathology compared to the remaining sample. Among fluid biomarkers, CSF p-tau217 showed the strongest association. Neuroimaging revealed elevated frontoparietal Aβ PET, alongside temporal, insular, and frontal tau PET deposition. Sensitivity analyses showed that, at the same threshold of memory decline, decreased ACD reflects greater AD pathology. DISCUSSION Standardized assessment of cognitive awareness, integrating objective neuropsychological performance with subjective reports, may provide a crucial extension of current clinical frameworks.

ABSTRACT.Severe febrile illness (SFI), a major cause of child mortality in Sub-Saharan Africa (SSA), is frequently caused by bloodstream infections (BSI), increasingly caused by antimicrobial-resistant organisms. However, antimicrobial resistance (AMR) prevalence and patterns in this population are largely unknown. We conducted a prospective cohort study of children aged 28 days to 14 years with SFI at a referral hospital in Tanzania (July 2022–September 2023) to determine the prevalence, pathogen profile, and AMR patterns of BSIs. Blood cultures were performed on all participants. Isolates underwent AMR testing and whole genome sequencing (WGS) to identify AMR genes and assess genetic relatedness. The association between BSI and mortality was assessed using logistic regression. Among the 392 enrolled children (median age 17.8 months), 5.2% (n = 20) had culture-confirmed BSI, with a case fatality rate of 45%. Gram-negative bacteria predominated (Escherichia coli, Klebsiella pneumoniae), with 79% of isolates exhibiting phenotypic resistance to ceftriaxone, a first-line antimicrobial. WGS revealed extended–spectrum β-lactamase genes (CTX-M-15, CTX-M-27) in most Enterobacterales isolates and identical isolates among 2/4 patients with Streptococcus pneumoniae and 2/3 Candida albicans infections. Children with BSI had significantly higher mortality than those without BSI (adjusted odds ratio 3.9; 95% CI: 1.5–10.1, P <0.01). These findings emphasize the urgent need for expanded AMR surveillance systems, empiric antibiotic regimens tailored to local AMR patterns, and culture-independent diagnostics in SSA. These data are critical for understanding the cause of severe infection and have the potential to guide policy aimed at reducing child mortality from BSI.

Plasma biomarkers have emerged as robust indicators of Alzheimer's disease (AD) pathology, offering accessible tools for staging and stratification. However, their expression across globally diverse populations remains poorly characterized. The aim of this study was to evaluate whether the combination of plasma biomarkers could distinguish different stages along the AD continuum and assess their clinical associations in a Latin American cohort. We evaluated plasma amyloid, tau, and neurodegeneration (ATN) biomarkers in 318 older adults from a Chilean community- and clinic-based cohort, including individuals with subjective cognitive complaints (SCC), mild cognitive impairment (MCI), and Alzheimer's disease dementia (ADD), alongside cognitively unimpaired (CU) participants. Plasma ATN biomarkers (Aβ42/Aβ40, p-tau217, NfL, and GFAP) were quantified using Simoa technology. Global cognition was assessed with the Addenbrooke's Cognitive Examination (ACE), memory with the Free and Cued Selective Reminding Test (FCSRT), and functional ability with the Technology-Activities of Daily Living Questionnaire (T-ADLQ). Group differences in plasma biomarkers were examined using ANCOVA models adjusted for age, sex, and education, and associations with cognitive performance were evaluated through linear regression analyses. In addition, supervised machine-learning models were implemented to classify participants across diagnostic categories based on plasma biomarker profiles, using cross-validation to evaluate predictive performance. We observed a progressive decline in the Aβ42/Aβ40 ratio and elevations in p-tau217 and GFAP across the clinical continuum. Additionally, p-tau217 and NfL levels were inversely associated with cognitive, memory, and functional performance. Notably, p-tau217 distinguished ADD from CU with high accuracy (AUC = 0.88), although its performance in earlier stages was limited. These findings support the biological consistency of plasma biomarkers in AD-related neurodegeneration and provide novel evidence from a Latin American population. Further studies are needed to improve early-stage detection and to better understand how genetic, environmental, and health factors shape biomarker expressions in underrepresented regions.