The DAWN study aims to investigate Alzheimer's disease (AD) genetics and underlying biological markers in a global population including African Americans (AA: 4,000) and Hispanic/Latinos (HI: 4,000) ascertained in the US and indigenous Africans (AF: 5,000) through collaboration with the African Dementia Consortium (AfDC) from 10 African counties. These 13,000 participants include AD cases and individuals with mild (MCI) or no cognitive impairment (NCI). To understand the underlying blood-based AD biomarkers profile of this unique cohort, we are analyzing the plasma levels of pTau181, neurofilament light chain (NFL), and Glial fibrillary acidic protein (GFAP). We measured pTau181 and NFL, and GFAP with Simoa chemistry using the pTau181 AdvantageV2 and NEUROLOGY 4-PLEX A assays, respectively, on the Quanterix HD-X instrument. Our preliminary cohort consisted of 174 AF (86 AD; 88 NCI) from Nigeria and Ghana study sites, 254 AA (24 AD; 102 MCI; 85 NCI), and 166 HI (44 AD; 61 MCI; 62 NCI). Linear mixed-effect regression models adjusted for age, sex, population substructure and relatedness followed by Bonferroni correction were applied to identify biomarker differences. There were no significant differences between the ancestral groups within the diagnostic categories for any of the biomarkers measured. Plasma pTau181 concentrations were increased in AD relative to NCI in all three populations ( p  = 5.1x10 -4 , 9.6x10 -5 , 5.1x10-4 in AA, AF, and HI respectively) and AD relative to MCI ( p  = 0.012, 0.0014 in AA and HI respectively), though no differences were noted between MCI and NCI. Interestingly, GFAP and NFL were highly significantly increased in AF AD vs NCI ( p  = 4.5x10 -9 , 7.9x10 -7 for GFAP and NFL respectively) and in HI ( p  = 7.9x10 -8 , 1.6x10 -6 for GFAP and NFL respectively), but no differences noted in AA. These results suggest AD biomarkers are generalizable across global populations, with baseline values being consistent. However, there are notable differences, particularly in NFL and GFAP levels, which may reflect underlying differences in environmental or genetic influences on AD. Ultimately, increasing sample sizes and combining genomic, biomarker, and social and environmental data will increase understanding of genetic risk of AD.

In low- and middle-income countries, Alzheimer's disease (AD) constitutes a growing public health burden. However, AD biomarkers research remains underrepresented in African populations. This study assesses core biomarkers of AD and their relevance in the African context as potential aid in clinical diagnosis. Nigerian older adults from VALIANT cohort (n = 967) underwent biomarker quantification in plasma (p-tau217, GFAP, NfL, Aβ42 and Aβ40) employing both the Single Molecule Assay (Simoa, Quanterix) and Nucleic acid-Linked Immuno-Sandwich Assay (NULISA, Alamar). Biomarkers were associated with disease severity in clinical-diagnostic and clinical-biological groups, with stepwise increases of p-tau217, NfL and GFAP from cognitively unimpaired to dementia (p < 0.05). Results were consistent across platforms. Comparison between sexes showed higher biomarker levels in male participants across diagnostic groups. A significant effect of apoE-E4 proteotype on p-tau217 levels, after adjusting for age and sex was identified. These findings support the application of plasma AD biomarkers in the African context and the relevance of further AD biomarker research in diverse populations.

BACKGROUND:The relationship between physical and cognitive health among Africans, known for a rising incidence of frailty, cardiometabolic, and cognitive disorders, is unclear. We investigated the relationship between hand grip strength (HGS), and cognitive impairment among older adults in an urban settlement in Ibadan, South West Nigeria. METHODS:In this study, we assessed 608 participants from the Vascular heAlth, fraiLty, and cognItion in Ageing Nigerians sTudy [VALIANT] - a population-based cohort of 1021 older persons in Ibadan, a city in Southwestern Nigeria. They were recruited through a multi-stage, stratified cluster random sampling method. Data on HGS were obtained using a digital hand dynamometer while cognitive function was assessed via a consensus diagnosis. The relationship between cognitive impairment and HGS was investigated using a multivariable-adjusted logistic regression analysis. RESULTS:The mean (SD) age of the study participants was 64.6 ± 11.5 years and 67.6% were females. The proportion of participants with cognitive dysfunction was 22.9%, while the mean (SD) HGS (in kg) was 18.16 (8.06). The mean (SD) HGS was lower among participants with cognitive dysfunction (13.44 ± 5.45) compared to those without cognitive impairment (19.58 ± 8.38; p-value <0.001). After adjustment for age, sex, clinical frailty, level of education, and other metabolic risk markers, high HGS showed a protective association with cognitive impairment, aORs (95%CI) 0.91 (0.87-0.95). This protective association [aORs (95% CI)] was consistent for individuals aged <65 years [0.87 (0.80-0.94] and ≥65 years [0.90 (0.85-0.96)], as well as males 0.88 (0.78-0.99) and females 0.91 (0.84-0.99). CONCLUSIONS:HGS was independently associated with cognitive impairment, buttressing the intricate link between physical and cognitive health in this unique West African population. Future work will explore the predictive ability of grip strength as an early indirect non-invasive biomarker of incident cognitive decline and the utility of targeted resistance training exercises in the primary prevention of neurocognitive disorders.

BackgroundSubjective cognitive complaints are common in older populations and may signpost incident Alzheimer's disease and related dementias.ObjectiveTo determine the frequency and predictors of cognitive impairment and dementia among Yoruba-speaking community dwelling older persons (65 years and above) from 2 communities in Oyo State, Southwest Nigeria who have Subjective cognitive complaints.MethodsThis was a cross-sectional, observational study conducted within two urban communities in Oyo State, South West Nigeria and involving 150 consenting and voluntarily participating elderly participants aged 65 years and above who had subjective cognitive complaints. Demographic and clinical data were obtained using a pro forma. Participants also had cognitive screening and a focused clinical examination by a physician. Categorization following consensus diagnosis was according to International Classification of Diseases version 11 (ICD-11) namely dementia, mild cognitive impairment and no cognitive impairment.ResultsThere were no statistically significant differences in the socio-demographic and cognitive performance scores on neuropsychological testing across sites. At final diagnosis, 4 participants had dementia (2.7%) while 15 participants (10%) had mild cognitive impairment. On logistic regression, only moderate-severe decline on the Clinical Dementia Rating Scale was significantly associated with higher odds of cognitive decline in this sample.ConclusionsAbout 1 in 7 older persons in this study already had objective cognitive decline. Subjective cognitive complaints in older Yoruba Africans should prompt early screening. Prospective studies to identify the consistent predictors of cognitive decline in this population are needed.

The neuropathological characterization of Alzheimer disease and related dementias (ADRD) has expanded globally through biofluid-based biomarker research, with increasing focus on less invasive novel plasma biomarkers. However, data on ADRD biomarkers among indigenous Africans(IA) remain limited. Further, the influence of social determinants of health (SDOH), vascular risk factors(VRFs), and lifestyle determinants on ADRD biomarkers among Africans is unclear. To address this, we investigated plasma concentrations of five key ADRD biomarkers in a large community-based cohort of older Nigerians, examining their associations with lifestyle factors, SDOH and VRFs. The Vascular heAlth, fraiLty, and cognItion in Ageing Nigerians (VALIANT) is a longitudinal community-based study conducted in Ibadan Northeast Local Government Area, Oyo State, Nigeria. A total of 1,036 participants were recruited through multi-stage, stratified cluster random sampling method, and underwent cognitive and functional assessments. Plasma concentrations of AD biomarkers (Aβ40, Aβ42, NfL, GFAP and p -Tau 217) were measured with single-molecule-assay (SIMOA) technology, and the data square-root transformed. Multiple linear regression models assessed the associations between biomarker levels and 18 independent covariates, including age, sex, VRFs, diet, physical strength, and social network scale. p -value <0.05 was deemed statistically significant. AD biomarker data were available for 1026 participants (age range: 50-107 yrs; mean age: 65+/-10.8yrs;27.2% male). At baseline, 3.4% of participants had dementia, and 11% had mild cognitive impairment (MCI), while the majority were cognitively unimpaired. All ADRD biomarkers varied significantly by age, sex (higher in males) and hand grip strength. Notably, Aβ40 and GFAP were independently influenced by social network scale, suggesting potential social determinants of amyloid deposition and astrocytic activation. Diabetes mellitus and regular intake of green leafy vegetables significantly impacted NfL levels, indicating metabolic contributions to axonal degeneration. Dyslipidemia, BMI, and educational attainment were independently associated with GFAP expression, highlighting metabolic and cognitive influences on neuroinflammatory pathways. This study provides novel insights into how sociodemographic factors, diet, VRFs, and SDOH influence AD biomarker expression in IAs. The observed associations with amyloid deposition (Aβ40), neuroinflammation (GFAP), and axonal integrity (NfL) highlight distinct mechanistic pathways that warrant further investigation. Future work will evaluate associations with cognitive and clinical outcomes.

INTRODUCTION:Neuropathological studies indicate a strong association between Alzheimer's disease (AD) and stroke, yet the molecular mechanisms underlying this association remain unclear. METHODS:Local genetic correlation analysis was conducted with LAVA (Local Analysis of [co]Variant Annotation) using the results from genome-wide association studies on AD and stroke in individuals of African ancestry. Enhanced Hi-C Capture Analysis (eHiCA) examined chromatin interactions using induced pluripotent stem cell (iPSC) -derived cells from AD brain autopsy samples. RESULTS:LAVA identified a region shared between AD and stroke on chromosome 18q21.33(rg = 0.77, p = 2.41×10-6). eHiCA demonstrated that the AD and stroke loci interact with regulatory elements in PHLPP1. Variants at PHLPP1 were also associated with AD in an independent set of individuals of African ancestry (p = 4.56 × 10-5). DISCUSSION:This study identified a region on top of PHLPP1 as a locus associated with both AD and stroke. PHLPP1 inhibits protein kinase B, which contributes to both AD and stroke pathophysiology.

Abstract Alzheimer’s disease and related dementia (ADRD) represents a growing public health burden, especially in low- and middle-income countries. Yet, most studies focus on Non-Hispanic white (NHW) populations from high-income countries. This study investigates plasma proteomic signatures associated with amyloid pathology in African populations. Nigerian older adults from the VALIANT study and participants from a Tanzanian study, with available biomarker quantification in plasma are employed. For proteomic comparison, participants from the Canadian TRIAD cohort are included, capturing a distinct population. Here, we show that multiple proteins are differentially abundant in the plasma of p-tau217-positive individuals and in the different cognitive groups, with findings largely consistent amongst African cohorts. Comorbidities are significantly associated with protein levels and differences in plasma biomarkers levels are found between sexes. Lastly, VALIANT and TRIAD show both shared and unique protein profiles in relation to amyloid-pathology. These findings support the utility of fluid biomarkers in ADRD in African populations.

Background: Genomic research in dementia in Africa is of utmost importance based on recent reports from studies on African-Americans that the African ancestral gene is associated with a lower risk effect for developing AD. However, dementia-related genetic studies are still evolving in sub-Saharan Africa, with unique challenges influencing participant recruitment. Objective: This study sought to identify key challenges of recruitment and retention how they were mitigated in the READD-ADSP Africa and 'Origins of AD in African ancestry' genetic studies. Methods: A qualitative narrative research design using in-depth interviews explored the challenges of recruiting participants and how these were managed by the nineteen stakeholders involved in the recruitment process from nine African countries participating in the African Dementia Consortium. An inductive thematic analysis was applied to code and analyze the data systematically. Results: Nineteen stakeholders from nine African countries, participating in READD-ADSP and 'Origins' studies were interviewed. Similar challenges were observed across most African countries, including the non-existing national dementia registry. Other challenges include language diversity, myths around blood collection, family dynamics, stigma, logistics, unmet expectations concerning incentives, fewer older controls and data privacy. Leveraging previous research programs, existing community engagement activities and client-doctor relationships were strategies used in addressing these challenges. Conclusions: There are some unique challenges with recruiting and retaining participants in genetic studies in Africa. Strengthening community engagement and advocacy for genomic research, alongside a well-populated dementia registry in the African Dementia Consortium, could overcome these challenges and improve participant recruitment in genetic studies.

The escalating prevalence of dementia in Africa, propelled by rapidly ageing population, necessitates innovative approaches to raise awareness and address associated challenges. The prevalent misconception of dementia as a result of witchcraft or wizardry is a challenge, and the media acts as a key agent in dispelling such myths. By reaching divers audiences, the media reinforces the notion that dementia is not confined to Africa alone but it is a global concern. It also aids in overcoming the shame and stigma associated with dementia, encouraging individuals to seek consultation. A comprehensive analysis of media initiatives used by the African Dementia Consortium (AfDC) during the World Alzheimer’s Month and subsequently was conducted. Digital Platforms (Instagram, LinkedIn, Facebook), print and traditional media (publications, journals, newspaper, radio and television stations) were examined for their effectiveness in achieving recruitment objectives, destigmatizing and promoting early diagnosis. Quality tools, such as cameras and recorders, were utilized to capture relevant information, while the outcome was evaluated based on their impact on target audience assessed by greater participation. Media Platforms have proven instrumental in recruitment efforts by disseminating information that reaches diverse demographic groups in Africa. Through compelling visual and textual content, the media has played a key role in destigmatizing dementia, challenging prevalent misconceptions, and fostering a more inclusive understanding of the condition. In addition, media initiatives have contributed significantly to the promotion of early diagnosis by disseminating educational content that empowers individuals to recognize early signs and seek timely medical intervention. Both the digital and traditional media play vital roles in visually and textually representing dementia, correcting misconceptions, and fostering understanding. Allocating increased resources to media initiatives hold immense benefit for Africa, contributing to a more positive perspective on dementia and dispelling negative attitudes.

Socioeconomic factors, including employment status and housing stability, are critical determinants of health outcomes. Economic hardship increases health risks by limiting healthcare access, exacerbating stress, and contributing to poorer mental and physical health. Employment status influences access to healthcare and financial security, while housing instability is linked to psychological distress and chronic disease. This study examines the association between cognitive health diagnoses (Non-Cognitively Impaired, MCI, AD, Dementia, Other or No Diagnosis) and key socioeconomic factors, including employment and housing stability. A quantitative analysis was conducted using two regional samples from the U19 READ-ADSP DAWN Study: Western Africa ( n  = 598) and Eastern Africa ( n  = 631). Assessed variables included employment status (full-time, part-time, retired, unemployed seeking/not seeking work), unemployment benefits/government assistance (Yes/No), housing security (worry about losing housing: Yes/No), and cognitive health diagnosis (Non-Cognitively Impaired, MCI, AD, Dementia, Other or No Diagnosis). Pearson's chi-square tests, Wilcoxon rank sum tests, and logistic regression models were used to evaluate associations between socioeconomic factors and health outcomes. In the Eastern region, employment status was significantly associated with primary diagnosis (χ 2 = 16.399, df = 4, p  = 0.0025), while unemployment benefits were not (χ 2 = 0.502, df = 1, p  = 0.4785). Housing insecurity was significantly associated with cognitive health diagnosis (χ 2 = 8.356, df = 1, p  = 0.0038), with logistic regression indicating that stable housing reduced the odds of receiving a cognitive health diagnosis (β = -0.857, SE = 0.296, p  = 0.0038). In the Western region, employment status was strongly associated with primary diagnosis (χ 2 = 75.87, df = 4, p  < 0.001), while unemployment benefits were not (χ 2 = 0.06857, df = 1, p  = 0.793). Housing stability significantly differed between cognitive health diagnosis groups (W=52544, p  = 0.0001), with housing security also showing a strong association (χ 2 = 8.3559, df = 1, p  = 0.0038). Logistic regression revealed that unemployment, retirement, and not seeking work significantly increased the likelihood of a primary diagnosis ( p  < 0.001). Findings highlight employment and housing stability as key social determinants influencing cognitive health, emphasizing the need for policies that enhance economic security to mitigate dementia risk.

The DAWN Alzheimer's Research Study is a multi-site international project to recruit African-American, Hispanic/Latino, and African participants for genomic studies of Alzheimer's Disease (AD). In addition to clinical evaluations, cognitive assessments and biomarker data collection, array-based representative genotyping is being performed for all participants. To increase the value of these genotypic data a vastly richer dataset can be created using imputation, a process that requires a whole genome sequenced reference dataset. High quality imputation depends on having large reference datasets representative of the ancestries of the target dataset. Using inadequate reference datasets results in low imputation quality, fewer usable imputed variants and hinders downstream analysis. Given the inclusion of African-ancestry participants (whose reference datasets are small) in the DAWN study, we examined the impact of using different strategies on the accuracy of genotype imputation. Using DAWN study data generated by the Illumina Global Screening Array, we performed genotype imputation using the TopMED R3 dataset and compared these results to a meta-imputation workflow using TopMED R3 supplemented by the Africa 6K dataset. This comparison explicitly tests the impact of increasing African ancestry in the imputation reference panel. Imputation results were assessed for chromosomes 1, 10, and 20 for total count of imputed variants, and by comparing variant counts across a range of imputation quality (R2) and variant rarity (MAF) filter criteria to identify apparent trends. An additional 190,784 (0.3%) variants are captured from the meta-imputed (64,370,296) vs the single-imputed (64,179,512) dataset. Variant quality also improves, with an increase of ∼80,000 (5%) filter-passing variants (R2 > 0.8) in the meta-imputation compared to the TopMED-only imputation results (Figure 1). The use of meta-imputation to better match the genetic background of the DAWN dataset through the use of multiple imputation references significantly increases the density and quality of the resulting genotypic dataset, enabling more powerful studies of AD genetics. This demonstrates the utility of meta-imputation for better matching the genetic background of samples when performing imputation.

INTRODUCTION:Alzheimer's disease (AD) remains a major neurocognitive disorder of global health significance. Globalizing ancestral diversity in AD genetics is essential to identify causal variants, improve diagnosis, and enable equitable therapeutic interventions across populations. The Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP) initiative addresses this by including African ancestry and Hispanic/Latinx (HL) ancestry populations. METHODS:READD-ADSP, a case-control study, aims to recruit, evaluate, and retain 13,000 participants: 5000 Indigenous Africans, 4000 African Americans, and 4000 Hispanic/Latinix individuals. In Africa, recruitment involves nine sub-Saharan African countries under the African Dementia Consortium, and with protocols ensuring standardized data collection, phenotype harmonization, culturally informed diagnostic algorithms, and robust community engagement. RESULTS:Study pparticipants are recruited, ascertained and retained. Blood samples and fractions (DNA, plasma, RNA) are biobanked for genomic, epigenomic, proteomic, and transcriptomic analyses. DISCUSSION:This study will advance precision ADRD medicine and establish a model for working with diverse global cohorts of brain disorders. Highlights:Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP) addresses critical gaps in Alzheimer's Disease and Related Dementias (ADRD) research by including underrepresented groups.The study recruits 13,000 participants of African, African American, and Hispanic/Latinx ancestries.Standardized protocols enable rigorous phenotyping and harmonization across diverse populations.Findings will inform precision medicine and reduce health disparities in ADRD outcomes.

INTRODUCTION:Apolipoprotein E (APOE) and ABCA7 genes are among the strongest heritable risk factors for Alzheimer's disease (AD) in African-ancestry (AA) populations. APOE 𝜀4 affects both risk and age at onset (AAO), with lower risk in AA populations. This study evaluates the independent and interactive effects of the AA-specific ABCA7 frameshift deletion and APOE 𝜀4 allele on AAO. METHODS:We analyzed 3510 AA individuals, including AD cases and controls. Cox regression models assessed the effects of ABCA7 deletion, APOE genotypes, and their interactive influence on AAO. RESULTS:APOE ε3/ε4 carriers with the ABCA7 deletion had a significantly shorter survival compared to ε3/ε4 carriers without the deletion. No significant differences were found between deletion carriers and non-carriers with APOE ε3/ε3 or ε4/ε4 genotypes. DISCUSSION:Our study showed that the ABCA7 deletion lowered the AAO of AD in APOE ε3/ε4 carriers from AA populations. These findings suggest that the AA-specific ABCA7 deletion and the APOE ε4 allele have synergistic effects on AAO. HIGHLIGHTS:AA-specific ABCA7 deletion lowers AAO of AD in APOE ε3/ε4 carriers from AA populations. Findings suggest an interaction between ABCA7 deletion and APOE ε4 on AAO. APOE ε4 has a strong, dose-dependent effect on AAO of AD in AA individuals. ABCA7 deletion impact on AAO of AD is stronger in females with APOE ε3/ε4.

Introduction: The African Rigorous Innovative Stroke Epidemiological Surveillance (ARISES) study is focused on developing an integrated mHealth community-based interactive Stroke Information and Surveillance System. This is the first paper to qualitatively investigate and contrast community beliefs, attitudes, and practices related to stroke prevention, risk factors and care from alternative/complementary medicine providers/healers, orthodox/modern medicine/health care providers, community members and leaders in Nigeria. Methods: Six focus groups with community members and leaders (n=57) and key informant interviews with health providers (n=24) from alternative/complementary medicine providers and orthodox/modern medicine providers were conducted to qualitatively explore beliefs, attitudes, practices, and recommendations related to stroke in urban (Ibadan) and rural (Ibarapa) communities in Nigeria. The Health Belief Model and Social Ecological Model guided the questions and thematic analysis of the qualitative data. Results: Participants perceived stroke as disabling though manageable but with odds of repeat stroke for survivors. High blood pressure, stress, sleep issues, heredity, and lifestyle factors were some stroke risk factors perceived by participants from both sites although God, witchcraft/evil people were reported by rural participants. Hospital visits and consumption of herbal concoction, self-medication and visit to church for prayers were some actions taken to manage stroke by both urban and rural participants. Low literacy levels, limited funds, fear of and distance to hospitals, and absence of insurance were some barriers to uptake of recommendations from orthodox medicine practitioners which are drivers to unorthodox practitioners. To improve stroke care and prevention across communities, free risk factor screening, indigenous stroke awareness programs via print, audio-visual and electronic media were suggested by all participants. Conclusion: Diverse beliefs and practices are related to stroke risk factors, prevention and care and barriers with obtaining care. There is need to work across systems to improve stroke prevention and care in communities.

Education is a crucial social determinant of health, influencing opportunities, socioeconomic status, and health outcomes. Regional disparities in educational attainment and their effects on cognitive health are especially notable in low- and middle-income countries (LMICs), where access to education and healthcare varies widely. This study explores the role of education in health disparities, focusing on two distinct African regions—Western and Eastern Africa—using data from the READD-ADSP DAWN Study. This cross-sectional study analyzed data from Western Africa ( n  = 756) and Eastern Africa ( n  = 689). Variables included early-life learning disability, special education participation, educational attainment (None, Elementary, High School, College, Graduate/Professional), and cognitive health diagnoses (Non-Cognitively Impaired, MCI, AD, Dementia, Other or No Diagnosis). A Wilcoxon rank sum test assessed differences in educational attainment between cognitive diagnostic groups. Logistic regression with a logit link function examined the relationship between years of education and the likelihood of a primary diagnosis of Alzheimer's Disease or Dementia. In the Eastern region sample, the Wilcoxon rank sum test revealed a significant difference in education levels between individuals with and without a cognitive health diagnosis (W=68233, p  <0.001). Logistic regression showed that education was a significant predictor of diagnosis (β=−0.04891, SE=0.01641, z=−2.980, p  = 0.00288). Higher education levels were associated with lower odds of a cognitive health diagnosis. The model fit was reasonable, with a residual deviance of 927.65 and an AIC of 931.65. In the Western region sample, the Wilcoxon rank sum test also showed a significant difference in education levels between individuals with and without a cognitive health diagnosis (W=81364, p  = 0.02669). Logistic regression confirmed that years of education significantly predicted diagnosis status (β=−0.02640, SE=0.01076, z=−2.454, p  = 0.0141), with higher education linked to lower odds of being diagnosed with a cognitive health diagnosis. The model fit was adequate, with a residual deviance of 1060.2 and an AIC of 1064.2. These findings further support the protective role of education against cognitive decline in both regions.

Understanding the genetic underpinnings of Alzheimer’s disease is crucial for advancing research and developing targeted interventions. Genomic research in dementia in Africa is of utmost importance based on recent reports from studies in African Americans that African ancestral gene is associated with lower risk effect for developing AD. However, dementia related genetic study is an evolving research in sub-Saharan Africa with peculiar challenges influencing participant recruitment. This study sought to identify the key challenges of the recruitment process into dementia- related genetic studies and how these were mitigated in the READD-ADSP Africa and Origins of AD in African ancestry genetic studies. A narrative qualitative research design using in-depth open-ended interviews explored the challenges of recruiting participants and how these were managed among the key stakeholders, including, healthcare professionals, and researchers involved in the recruitment process from nine African countries participating in the AfDC. An inductive thematic analysis was applied to systematically code and analyze the data. Eighteen stakeholders from 7 African country members (Nigeria, Ghana, Kenya, Tanzania, Uganda, Cameroon, and Ethiopia) of the AfDC were interviewed. Similar challenges were observed across most African Countries which includes non-existing national dementia registry, a common challenge in the recruitment process. Other challenges identified were poorly populated local or hospital-based dementia registry, language diversity, myths around blood collection, family dynamics, stigma, logistics, unmet expectations concerning incentives, fewer older controls and data privacy. Leveraging on previous research programmes, existing community engagement activities and client-doctor relationship assisted in addressing these challenges There are some unique challenges with recruitment of participants into genetic studies in Africa. Educating the populace on the need for genetic studies is key to addressing some of these challenges. Community engagement programs specifically targeted at improving knowledge about dementia are currently being deployed across these countries. Adopting culturally-sensitive recruitment strategies, strengthening community engagement and advocacy for well populated dementia registry for AfDC could further help address these obstacles and improve recruitment of participants in genetic studies.

Background:In low- and middle-income countries, Alzheimer's disease and related dementias (ADRD) constitute a growing public health burden. Indeed, the lack of awareness and easy screening tools, such as blood-based biomarkers, leaves many patients undiagnosed. In this study, we explored the core biomarkers of AD in an indigenous African cohort (VALIANT) to assess their relevance and potential utility to aid clinical diagnosis. Methods:Nigerian African older adults (n = 967; ≥50 years) participating in the VALIANT study completed a baseline cross-sectional evaluation with associated clinical diagnosis. We quantified phosphorylated tau (p-tau 217), glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and amyloid beta (Aβ42 and Aβ40) levels in plasma with both the Single Molecule Assay (SIMOA, Quanterix) and Nucleic acid-Linked Immuno-Sandwich Assay (NULISA, Alamar) platforms. Results:In agreement with previous findings, core AD biomarkers were associated with disease severity both in clinical diagnostic and clinico-pathological groups, with stepwise increases of p-tau 217, NfL and GFAP from cognitively unimpaired (CU) to dementia (p < 0.05). These results were consistent across both SIMOA and NULISA platforms. Comparison between sexes showed higher levels of biomarkers in male participants across diagnostic groups. We identified a significant effect of apoE E4 proteotype on p-tau217 levels after adjusting for age and sex but no significant effect on the other AD biomarkers. Conclusion:This first application of cutting-edge plasma AD biomarker immunoassay using two ultrasensitive platforms in an indigenous African cohort showed good concordance and underscores the relevance and utility of blood-based biomarkers of AD in diverse populations. Additionally, sex differences could unveil biological distinctions inherent in the African population.

Background:Inflammation might predispose to worse outcomes after an ischemic stroke. This has not been characterized among indigenous Africans. Purpose:We investigated the association between inflammatory biomarkers, stroke severity, and outcomes in Africans. Methods:This is a retrospective analysis of a prospective study, including 90 participants with confirmed ischemic stroke selected from the Stroke Investigative Research & Educational Network (SIREN) cohort and 90 controls matched by age, sex, and ethnicity. Plasma concentrations of 368 protein biomarkers were analyzed (Olink® Explore 384 Inflammation panel) and compared between cases and controls. Further, we investigated the association between these proteins and stroke severity, lesion volume, and one-month post-stroke disability and fatality. Results:Differential protein expression analysis revealed 23 up-regulated and 14 down-regulated proteins in stroke cases versus controls. Among the up-regulated proteins, agouti-related protein (AgRP) and tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) were the most significantly up-regulated, while interleukin-1 beta (IL-1β) and integrin alpha-11 (ITGA11) were the most down-regulated proteins. Logistic regression analysis identified 72 proteins that were associated with stroke severity independent of age and sex. Among these, complement C1q subcomponent subunit A (C1qa) exhibited the strongest associations. Additionally, 14 proteins including C-C motif chemokine 23 (CCL23) were found to be associated with one-month post-stroke disability. Conclusion:Stroke disability and severity were associated with inflammation in an indigenous African population. The identified biomarkers might be useful for predicting stroke outcome or serve as therapeutic target. Graphical abstract:

BACKGROUND:We investigated whether risk factors for intracerebral hemorrhage (ICH) among indigenous Africans (IA) would vary in prevalence and effect compared with self-reported African, Hispanic, and White Americans by comparing data from 2 independent population-based case-control studies conducted in West Africa and the United States. METHODS:We compared ICH risk factors common to the SIREN (Stroke Investigative Research and Educational Network: 1100 case-control pairs) and the ERICH (Ethnic/Racial Variation of Intracerebral Hemorrhage: 999 case-control pairs African American participants, 998 case-control pairs, Hispanic Americans, 1000 case-control pairs, White Americans) studies. Ethnicity/Race was self-reported. The effect measure of interest is the odds ratio (OR). To test for differences in the effects of the risk factors between the SIREN IA study population and each of the ERICH study populations, a test for heterogeneity was computed using the R program, metagen (version 4.9-6). RESULTS:ICH occurred at a younger age among IA (54.3±13.4 years), African Americans (58.0±12.7), and Hispanic Americans (58.9±14.3), compared with White Americans (69.1±13.9). The largest distinction was for hypertension, where IA exhibited a much larger risk of ICH than the American study population (OR, 67.02 [95% CI, 33.30-134.85]), African American (OR, 3.71 [95% CI, 2.53-5.44]); Hispanic (OR, 3.55 [95% CI, 2.54-4.92]), and White population (OR, 2.69 [95% CI, 1.95-3.69]). Current alcohol use exhibited increased risk in IA (OR, 2.24 [95% CI, 1.36-3.67]), but not in African Americans (OR, 0.63 [95% CI, 0.46-0.86]), Hispanic (OR, 0.87 [95% CI, 0.65-1.17]), and White Americans (OR, 0.51 [95% CI, 0.38-0.69]). CONCLUSIONS:Identical or comparable risk factors do not consistently result in the same disease risk across different cultures and regions. Therefore, to improve our understanding of the genetic determinants and biological pathways driving ICH risk, it is crucial to study multiple populations, including IA, while accounting for the influence of environmental and social factors.

The Recruitment and Retention for Alzheimer's Disease Diversity in the Alzheimer's Disease Sequencing Project (READD-ADSP) aims to recruit 5000 African participants (Alzheimer's disease [AD] and cognitively unimpaired controls) to generate genomic and biomarker data to better characterize AD neurobiology in Africa from countries that constitute the African Dementia Consortium (AfDC). Blood samples from study participants are separated into fractions and transported to the African Coordinating Centre (ACC: Ibadan, Nigeria), where DNA extraction and long-term biospecimen storage are carried out. Plasma and DNA aliquots are shipped to the John P. Hussman Institute for Human Genomics, University of Miami (HIHG-UM, Miami, USA) for genotyping, whole genome sequencing, and biomarker analysis. Innovative solutions were devised to mitigate challenges encountered so far. Our biobanking experience in a low-resource setting demonstrates the feasibility of establishing a successful African biobanking network, as an important infrastructure to support Alzheimer's disease and related dementias research in Africa.