Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.

INTRODUCTION: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses. RESULTS: A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, P = 3.68×10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10-7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD-associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. HIGHLIGHTS: Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies. The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa. Single variant meta-analysis identified a novel genome-wide significant AD-risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome-wide significance at P < 9×10-7. Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus. These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry-informed genetic screening tools and therapeutic interventions.

Dementia in Africa: Current evidence, knowledge gaps, and future directions.

In tandem with the ever-increasing aging population in low and middle-income countries, the burden of dementia is rising on the African continent. Dementia prevalence varies from 2.3% to 20.0% and incidence rates are 13.3 per 1000 person-years with increasing mortality in parts of rapidly transforming Africa. Differences in nutrition, cardiovascular factors, comorbidities, infections, mortality, and detection likely contribute to lower incidence. Alzheimer's disease, vascular dementia, and human immunodeficiency virus/acquired immunodeficiency syndrome-associated neurocognitive disorders are the most common dementia subtypes. Comprehensive longitudinal studies with robust methodology and regional coverage would provide more reliable information. The apolipoprotein E (APOE) ε4 allele is most studied but has shown differential effects within African ancestry compared to Caucasian. More candidate gene and genome-wide association studies are needed to relate to dementia phenotypes. Validated culture-sensitive cognitive tools not influenced by education and language differences are critically needed for implementation across multidisciplinary groupings such as the proposed African Dementia Consortium.

The African Stroke Organization Conference 2021: Building Capacity, Careers, Collaborations, and Contributions.

The inaugural African Stroke Organization Conference (ASOC) aimed to create a forum to discuss the latest stroke science, highlight opportunities to address the high burden of stroke in Africa, develop a viable pipeline of emerging African stroke researchers, honor leading scientists and policy makers, and provide networking avenues to bolster future collaboration. Using a virtual platform, ASOC was held from Nov 3-4, 2021, and was attended by 236 participants. ASOC 2021 sessions included: (1) Osuntokun Award Lecture delivered by Prof. Richard Walker of Newcastle University; (2) Distinguished Policy Maker Lecture delivered by Dr. Raj Tajudeen of the African Centers for Disease Control and Prevention; (3) Invited presentations by prominent global stroke academicians on acute stroke, vascular malformations, vascular brain injury, Covid-19, nursing/allied care, rehabilitation/recovery, health services, imaging, pediatric stroke, precision medicine, and unusual causes of stroke; (4) six oral scientific abstract presentations; and (5) fifteen moderated oral poster presentations. Other sessions were (i) Vascular Brain Trust where early career African scholars presented manuscripts and grant proposals under development for feedback from seasoned researchers (ii) Moving on Up during which presentations were given to early career scholars about pathways for success in funding and advancement. A capstone event was the Frontiers of Research in Africa session which showcased the work and capabilities of 20 scientists and sites in Africa. All the ASOC sessions were lively and post-conference feedback from attendees showed high levels of satisfaction for the conference platforms and content. The ASOC marks a new dawn in the era of an escalating stroke burden in Africa, and it is anticipated to serve as a catalyst for exponentially building the capacity, careers, collaborations, and contributions of Africans to ameliorating stroke within and beyond the continent.

Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.

BACKGROUND: The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases. METHODS: We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate. RESULTS: The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation. CONCLUSIONS: In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project.

BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18-60.5 months). Young-onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per-capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub-Saharan Africa. The registry will serve as a platform for development of multipronged evidence-based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria. © 2020 International Parkinson and Movement Disorder Society.

Prevention of stroke: a global perspective.

Along with the rising global burden of disability attributed to stroke, costs of stroke care are rising, providing the impetus to direct our research focus towards effective measures of stroke prevention. In this Series paper, we discuss strategies for reducing the risk of the emergence of disease (primordial prevention), preventing the onset of disease (primary prevention), and preventing the recurrence of disease (secondary prevention). Our focus includes global strategies and campaigns, and measurements of the effectiveness of worldwide preventive interventions, with an emphasis on low-income and middle-income countries. Our findings reveal that effective tobacco control, adequate nutrition, and development of healthy cities are important strategies for primordial prevention, whereas polypill strategies, use of mobile technology (mHealth), along with salt reduction and other dietary interventions, are effective in the primary prevention of stroke. An effective collaboration between various health-care sectors, government policies, and campaigns can successfully implement secondary prevention strategies, through surveillance and registries, such as the WHO's non-communicable diseases programmes, across high-income and low-income countries.

Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia.

White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood-brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1-28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood-brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia.

Impact of somatic comorbidities on quality of life of patients living with epilepsy in Sagamu, Nigeria.

PURPOSE: Somatic comorbidities are probably as important as the psychiatry comorbidities in people with epilepsy (PWE) although the former has received little attention especially in low- and middle-income countries where the incidence of epilepsy is high. The main objective of this study was to determine the frequencies of somatic comorbidities in PWE. We also compared quality of life of two groups of PWE: Those with somatic comorbidities and those without. METHODS: In this comparative cross-sectional study, consecutive adult patients with epilepsy above 18 years of age were recruited at the neurology outpatient clinic of Olabisi Onabanjo University Teaching Hospital from July 2010 through March 2011. Epilepsy-related data and somatic comorbidities were collated in this population. Health-related quality of life (HRQoL) and depression were also measured using QOLIE-31(version 1.0) and Becks depression inventory II (BDI-II), respectively. RESULTS: One hundred and two PWE were recruited with 31 (30.4%) having at least one somatic comorbidity. Hypertension (OR = 12.43), dyspepsia (OR = 8.16), and stroke (OR = undefined) were significantly prevalent among PWE who are ≥50 years old. Energy was significantly lower among patients with comorbidities, and patients with multiple comorbidities had worse quality of life than those with single comorbidity (P = 0.006). CONCLUSION: Somatic comorbidity is prevalent in this population with significant impact on their quality of life. We emphasize the need to screen for and reduce the numbers of somatic comorbidities in PWE as this can improve their quality of life.

Current perspectives on prevention of vascular cognitive impairment and promotion of vascular brain health.

INTRODUCTION: The true global burden of vascular cognitive impairment (VCI) is unknown. Reducing risk factors for stroke and cardiovascular disease would inevitably curtail VCI. AREAS COVERED: The authors review current diagnosis, epidemiology, and risk factors for VCI. VCI increases in older age and by inheritance of known genetic traits. They emphasize modifiable risk factors identified by the 2020 Lancet Dementia Commission. The most profound risks for VCI also include lower education, cardiometabolic factors, and compromised cognitive reserve. Finally, they discuss pharmacological and non-pharmacological interventions. EXPERT OPINION: By virtue of the high frequencies of stroke and cardiovascular disease the global prevalence of VCI is expectedly higher than prevalent neurodegenerative disorders causing dementia. Since ~ 90% of the global burden of stroke can be attributed to modifiable risk factors, a formidable opportunity arises to reduce the burden of not only stroke but VCI outcomes including progression from mild to the major in form of vascular dementia. Strict control of vascular risk factors and secondary prevention of cerebrovascular disease via pharmacological interventions will impact on burden of VCI. Non-pharmacological measures by adopting healthy diets and encouraging physical and cognitive activities and urging multidomain approaches are important for prevention of VCI and preservation of vascular brain health.

Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans.

BACKGROUND: African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans. METHODS: Cases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation. RESULTS: We observed genome-wide significant (P-value < 5.0E-8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E-6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E-6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E-6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping. CONCLUSIONS: Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke's risk prediction and development of new targeted interventions to prevent or treat stroke.

Sociodemographic and behavioural risk factors for obesity among community-dwelling older adults in Ghana and Nigeria: A secondary analysis of data from the SIREN study.

OBJECTIVES: To explore the prevalence and risk factors of obesity among older adults from low- and middle-income countries (LMICs). METHODS: This is a secondary analysis of data obtained from the SIREN study through in-person interviews and measurements from healthy stroke-free older adults (≥60 years). Overweight/obesity was defined as body mass index ≥25 kg/m2. Abdominal obesity was defined as waist-to-hip ratio (WHR) of >0.90 for males and >0.85/females or waist circumference (WC) of >102 cm for males/>88 cm for females. Adjusted odds ratio (aORs) with 95% confidence interval (CIs) of the relationship between obesity and sociodemographic factors were assessed at P < 0.05. RESULTS: Overall, 47.5% of participants were overweight/obese, 76.6% had a larger than recommended WHR, and 54.4% had a larger than recommended WC. Abdominal obesity (WC; aOR: 9.43, CI: 6.99-12.50), being a Nigerian (aOR: 0.55; CI: 0.42-0.72), living in an urban setting (aOR: 1.92; CI: 1.49-2.46), earning >$100/month (aOR: 1.53; CI: 1.19-1.96), and having formal education (aOR: 1.42; CI: 1.08-1.87) were associated with overweight/obesity. CONCLUSION: Living in urban settings, earning a higher income, and having a formal education were associated with a higher odds of obesity among older adults from LMICs.

Heart failure in Nigeria: protocol for a systematic review and meta-analysis.

Background: Heart failure is now a significant contributor to the burden of non-communicable diseases in developing countries like Nigeria which is experiencing epidemiologic and demographic transition. The epidemiology of heart failure in this country is poorly characterized. The aim of the review is to determine the prevalence of heart failure, the associated risk factors, the aetiology, management, and outcomes of the condition in the country. Methods: Relevant databases such as PubMed /Medline, EMBASE, Web of Science, Google Scholar, African Index Medicus, and African journal online would be searched for articles published in English from January 2000 to December 2021. The analysis will include observational studies conducted among Nigerian adults aged 12 years and above. Article selection shall be conducted by pairs of independent reviewers. Data extraction shall be done by 2 independent reviewers. Results: The primary outcome would be the pooled prevalence of heart failure while the secondary outcomes would be to identify the risk factors and management of heart failure in Nigeria. Conclusion: This will be the first systematic review and meta-analysis of heart failure epidemiology in Nigeria which will hopefully identify gaps for future research and guidance for policy interventions.

Capacity-Building for Stroke Genomic Research Data Collection: The African Neurobiobank Ethical, Legal, and Social Implications Project Experience.

Background: The fields of stroke genomics, biobanking, and precision medicine are rapidly expanding in sub-Saharan Africa. However, the ethical, legal, and social implications (ELSI) of emerging neurobiobanking and genomic data resources are unclear in an emerging African scientific landscape with unique cultural, linguistic, and belief systems. Objective: This article documents capacity-building experiences of researchers during the development, pretesting, and validation of data collection instruments of the African Neurobiobank for Precision Stroke Medicine-(ELSI) Project. Methods: The African Neurobiobank for Precision Stroke Medicine-ELSI project is a transnational, multicenter project implemented across seven sites in Ghana and Nigeria. Guided by the Community-Based Participatory Research framework, we conducted three workshops with key stakeholders to review the study protocol, ensure uniformity in implementation; pretest, harmonize, and integrate context-specific feedback to ensure validity and adaptability of data collection instruments. Workshop impact was assessed using an open-ended questionnaire, which included questions on experience with participation in any of the workshops, building capacity in Genetic and Genomic Research (GGR), level of preparedness toward GGR, the genomic mini-dictionary developed by the team, and its impact in enhancing understanding in GGR. Data were analyzed qualitatively using a thematic framework approach. Results: Findings revealed the usefulness of the workshop in improving participants' knowledge and capacity toward GGR implementation. It further identified local, context-specific concerns regarding quality data collection, the need to develop culturally acceptable, genomic/biobanking data collection tools, and a mini-dictionary. Participants-reported perceptions were that the mini-dictionary enhanced understanding, participation, and data collection in GGR. Overall, participants reported increased preparedness and interest in participating in GGR. Conclusion: Capacity-building is a necessary step toward ELSI-related genomic research implementation in African countries where scholarship of ELSI of genomics research is emerging. Our findings may be useful to the design and implementation of ELSI-GGR projects in other African countries.

Research participants' perception of ethical issues in stroke genomics and neurobiobanking research in Africa.

Background: There is a growing interest in stroke genomics and neurobiobanking research in Africa. These raise several ethical issues, such as consent, re-use, data sharing, storage, and incidental result of biological samples. Despite the availability of ethical guidelines developed for research in Africa, there is paucity of information on how the research participants' perspectives could guide the research community on ethical issues in stroke genomics and neurobiobanking research. To explore African research participants' perspectives on these issues, a study was conducted at existing Stroke Investigation Research and Education Network (SIREN) sites in Nigeria and Ghana. Method: Using an exploratory design, twenty-eight Focus Group Discussions (FGDs) sessions were conducted with stroke survivors (n=7), caregivers(n=7), stroke - free controls(n=7), and Community Advisory Board members(n=7). Data were collected using an interview guide. Interviews were conducted in English and indigenous languages of the community, audio recorded, and transcribed verbatim. Data were analyzed using NVivo (March, 2020) Software. Result: Results revealed that stroke genomics and neurobiobanking research in Africa require researchers' direct attention to ethical issues. Concerns were raised about understanding, disclosure and absence of coercion as components of true autonomous decision making in research participation. Participants argued that the risk and benefits attached to participation should be disclosed at the time of recruitment. Fears around data sharing were voiced as adherence to the principle of privacy and confidentiality were of paramount importance to participants. The preference was to receive the results of incidental findings with no stigma attached from society. Conclusion: Research participants' perspectives are a vital aspect of community engagement in stroke genomics and neurobiobanking research. Findings from this study suggest that research participants are interested in these fields of research in Africa if their concerns about ethical issues are appropriately addressed within the research framework.

Risk Assessment Score and Chi-Square Automatic Interaction Detection Algorithm for Hypertension Among Africans: Models From the SIREN Study.

BACKGROUND: This study aimed to develop a risk-scoring model for hypertension among Africans. METHODS: In this study, 4413 stroke-free controls were used to develop the risk-scoring model for hypertension. Logistic regression models were applied to 13 risk factors. We randomly split the dataset into training and testing data at a ratio of 80:20. Constant and standardized weights were assigned to factors significantly associated with hypertension in the regression model to develop a probability risk score on a scale of 0 to 1 using a logistic regression model. The model accuracy was assessed to estimate the cutoff score for discriminating hypertensives. RESULTS: Mean age was 59.9±13.3 years, 56.0% were hypertensives, and 8 factors, including diabetes, age ≥65 years, higher waist circumference, (BMI) ≥30 kg/m2, lack of formal education, living in urban residence, family history of cardiovascular diseases, and dyslipidemia use were associated with hypertension. Cohen κ was maximal at ≥0.28, and a total probability risk score of ≥0.60 was adopted for both statistical weighting for risk quantification of hypertension in both datasets. The probability risk score presented a good performance-receiver operating characteristic: 64% (95% CI, 61.0-68.0), a sensitivity of 55.1%, specificity of 71.5%, positive predicted value of 70.9%, and negative predicted value of 55.8%, in the test dataset. Similarly, decision tree had a predictive accuracy of 67.7% (95% CI, 66.1-69.3) for the training set and 64.6% (95% CI, 61.0-68.0) for the testing dataset. CONCLUSIONS: The novel risk-scoring model discriminated hypertensives with good accuracy and will be helpful in the early identification of community-based Africans vulnerable to hypertension for its primary prevention.

Extended genome-wide association study employing the African Genome Resources Panel identifies novel susceptibility loci for Alzheimer's Disease in individuals of African ancestry.

INTRODUCTION: Despite a two-fold increased risk, individuals of African ancestry have been significantly underrepresented in Alzheimer's Disease (AD) genomics efforts. METHODS: GWAS of 2,903 AD cases and 6,265 cognitive controls of African ancestry. Within-dataset results were meta-analyzed, followed by gene-based and pathway analyses, and analysis of RNAseq and whole-genome sequencing data. RESULTS: A novel AD risk locus was identified in MPDZ on chromosome 9p23 (rs141610415, MAF=.002, P =3.68×10 -9 ). Two additional novel common and nine novel rare loci approached genome-wide significance at P <9×10 -7 . Comparison of association and LD patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 ( ASCL1 ), suggesting that the association is modulated by regional origin of local African ancestry. DISCUSSION: Increased sample sizes and sample sets from Africa covering as much African genetic diversity as possible will be critical to identify additional disease-associated loci and improve deconvolution of local genetic ancestry effects.

Neuroimaging standards for research into small vessel disease-advances since 2013.

Cerebral small vessel disease (SVD) is common during ageing and can present as stroke, cognitive decline, neurobehavioural symptoms, or functional impairment. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive and other symptoms and affect activities of daily living. Standards for Reporting Vascular Changes on Neuroimaging 1 (STRIVE-1) categorised and standardised the diverse features of SVD that are visible on structural MRI. Since then, new information on these established SVD markers and novel MRI sequences and imaging features have emerged. As the effect of combined SVD imaging features becomes clearer, a key role for quantitative imaging biomarkers to determine sub-visible tissue damage, subtle abnormalities visible at high-field strength MRI, and lesion-symptom patterns, is also apparent. Together with rapidly emerging machine learning methods, these metrics can more comprehensively capture the effect of SVD on the brain than the structural MRI features alone and serve as intermediary outcomes in clinical trials and future routine practice. Using a similar approach to that adopted in STRIVE-1, we updated the guidance on neuroimaging of vascular changes in studies of ageing and neurodegeneration to create STRIVE-2.

Global synergistic actions to improve brain health for human development.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization's new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022-2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a 'neurological revolution' across four key pillars - surveillance, prevention, acute care and rehabilitation - termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

Non-Communicable Neurological Disorders and Neuroinflammation.

Traumatic brain injury, stroke, and neurodegenerative diseases represent a major cause of morbidity and mortality in Africa, as in the rest of the world. Traumatic brain and spinal cord injuries specifically represent a leading cause of disability in the younger population. Stroke and neurodegenerative disorders predominantly target the elderly and are a major concern in Africa, since their rate of increase among the ageing is the fastest in the world. Neuroimmunology is usually not associated with non-communicable neurological disorders, as the role of neuroinflammation is not often considered when evaluating their cause and pathogenesis. However, substantial evidence indicates that neuroinflammation is extremely relevant in determining the consequences of non-communicable neurological disorders, both for its protective abilities as well as for its destructive capacity. We review here current knowledge on the contribution of neuroinflammation and neuroimmunology to the pathogenesis of traumatic injuries, stroke and neurodegenerative diseases, with a particular focus on problems that are already a major issue in Africa, like traumatic brain injury, and on emerging disorders such as dementias.

Primary stroke prevention worldwide: translating evidence into action.

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.