The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Biomarkers and Risk Assessment of Alzheimer's Disease in Low- and Middle-Income Countries.

Dementia is a chronic syndrome which is common among the elderly and is associated with significant morbidity and mortality for patients and their caregivers. Alzheimer's disease (AD), the most common form of clinical dementia, is biologically characterized by the deposition of amyloid-ß plaques and neurofibrillary tangles in the brain. The onset of AD begins decades before manifestation of symptoms and clinical diagnosis, underlining the need to shift from clinical diagnosis of AD to a more objective diagnosis using biomarkers. Having performed a literature search of original articles and reviews on PubMed and Google Scholar, we present this review detailing the existing biomarkers and risk assessment tools for AD. The prevalence of dementia in low- and middle-income countries (LMICs) is predicted to increase over the next couple of years. Thus, we aimed to identify potential biomarkers that may be appropriate for use in LMICs, considering the following factors: sensitivity, specificity, invasiveness, and affordability of the biomarkers. We also explored risk assessment tools and the potential use of artificial intelligence/machine learning solutions for diagnosing, assessing risks, and monitoring the progression of AD in low-resource settings. Routine use of AD biomarkers has yet to gain sufficient ground in clinical settings. Therefore, clinical diagnosis of AD will remain the mainstay in LMICs for the foreseeable future. Efforts should be made towards the development of low-cost, easily administered risk assessment tools to identify individuals who are at risk of AD in the population. We recommend that stakeholders invest in education, research and development targeted towards effective risk assessment and management.

Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study.

BACKGROUND: An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson's disease in these underserved populations. METHODS: We performed a genome-wide association study (GWAS) in people of African and African admixed ancestry with and without Parkinson's disease. Individuals were included from several cohorts that were available as a part of the Global Parkinson's Genetics Program, the International Parkinson's Disease Genomics Consortium Africa, and 23andMe. A diagnosis of Parkinson's disease was confirmed clinically by a movement disorder specialist for every individual in each cohort, except for 23andMe, in which it was self-reported based on clinical diagnosis. We characterised ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation, and enzymatic activity. FINDINGS: We included 197 918 individuals (1488 cases and 196 430 controls) in our genome-wide analysis. We identified a novel common risk factor for Parkinson's disease (overall meta-analysis odds ratio for risk of Parkinson's disease 1·58 [95% CI 1·37-1·80], p=2·397 × 10-14) and age at onset at the GBA1 locus, rs3115534-G (age at onset ß=-2·00 [SE=0·57], p=0·0005, for African ancestry; and ß=-4·15 [0·58], p=0·015, for African admixed ancestry), which was rare in non-African or non-African admixed populations. Downstream short-read and long-read whole-genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. The identified signal seems to be associated with decreased glucocerebrosidase activity. INTERPRETATION: Our study identified a novel genetic risk factor in GBA1 in people of African ancestry, which has not been seen in European populations, and it could be a major mechanistic basis of Parkinson's disease in African populations. This population-specific variant exerts substantial risk on Parkinson's disease as compared with common variation identified through GWAS and it was found to be present in 39% of the cases assessed in this study. This finding highlights the importance of understanding ancestry-specific genetic risk in complex diseases, a particularly crucial point as the Parkinson's disease field moves towards targeted treatments in clinical trials. The distinctive genetics of African populations highlights the need for equitable inclusion of ancestrally diverse groups in future trials, which will be a valuable step towards gaining insights into novel genetic determinants underlying the causes of Parkinson's disease. This finding opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk of Parkinson's disease. FUNDING: The Global Parkinson's Genetics Program, which is funded by the Aligning Science Across Parkinson's initiative, and The Michael J Fox Foundation for Parkinson's Research.

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018.

BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

Gender and educational attainment influence willingness to donate organs among older Nigerians: a questionnaire survey.

INTRODUCTION: disparity between the demand for and the supply of organs for transplantation remains a major public health issue of global concern. This study evaluated the knowledge and determinants of willingness to donate organs among outpatient clinic attendees in a Nigerian teaching hospital. METHODS: a 43-item semi-structured interviewer-administered questionnaire was designed to assess awareness and willingness of individuals attending Neurology, Psychiatry and Geriatrics Outpatient clinics to donate bodily organs for transplantation. Association between participants' characteristics and willingness towards organ donation was investigated using logistic regression models. RESULTS: a total of 412 participants were interviewed and mean age was 46.3 (16.1) years. There were 229 (55.6%) females and 92.5% had at least 6 years of formal education. Overall, 330 (80.1%) were aware of donation of at least one organ for transplantation purposes but only 139 (33.7%) were willing to donate organ. In analyses, adjusting for sex, marital status, family setting and educational status, male gender AOR [2.066(1.331-3.2016)] secondary education [AOR 5.57 (1.205-25.729) p= 0.028] and post-secondary education [AOR-6.98 (1.537-31.702) p= 0.012 were independently associated with willingness towards organ donation. CONCLUSION: the survey revealed high level of awareness but poor willingness towards organ donation among older Nigerians attending outpatient clinics of a premier tertiary hospital. Male gender and educational attainment were significantly associated with willingness to donate. Educational programs that particularly target women and less educated older Nigerians are needed to promote organ donation in Nigeria.

Strategies to Improve Stroke Care Services in Low- and Middle-Income Countries: A Systematic Review.

BACKGROUND: The burden of stroke in low- and middle-income countries (LMICs) is large and increasing, challenging the already stretched health-care services. AIMS AND OBJECTIVES: To determine the quality of existing stroke-care services in LMICs and to highlight indigenous, inexpensive, evidence-based implementable strategies being used in stroke-care. METHODS: A detailed literature search was undertaken using PubMed and Google scholar from January 1966 to October 2015 using a range of search terms. Of 921 publications, 373 papers were shortlisted and 31 articles on existing stroke-services were included. RESULTS: We identified efficient models of ambulance transport and pre-notification. Stroke Units (SU) are available in some countries, but are relatively sparse and mostly provided by the private sector. Very few patients were thrombolysed; this could be increased with telemedicine and governmental subsidies. Adherence to secondary preventive drugs is affected by limited availability and affordability, emphasizing the importance of primary prevention. Training of paramedics, care-givers and nurses in post-stroke care is feasible. CONCLUSION: In this systematic review, we found several reports on evidence-based implementable stroke services in LMICs. Some strategies are economic, feasible and reproducible but remain untested. Data on their outcomes and sustainability is limited. Further research on implementation of locally and regionally adapted stroke-services and cost-effective secondary prevention programs should be a priority.

Geriatric medicine: services and training in Africa.

BACKGROUND: the population is ageing globally and developing countries are experiencing the most rapid increase in the number of older persons. By 2045 the United Nations estimate that for the first time in history more people will be over 65, than under 15, years of age. The World Health Organization predicts that deaths from non-communicable diseases will rise by 24% in Africa in the next decade. The aim of this survey was to determine the specialist medical services available for older persons and the undergraduate and postgraduate training systems in place for geriatrics in each African country. METHODS: a short survey was developed and sent to representatives from every country. Where appropriate, French and Portuguese translations were available. RESULTS: responses were received from 40/54 countries (74%). Data were obtained via an internet search for a further three countries. Out of 43, 25 countries had no geriatricians. Out of 40, 35 countries had no formal undergraduate training for medical students on geriatrics and 33 of 40 countries reported no national postgraduate training scheme for geriatrics. Having at least one geriatrician in the country was associated with a World Bank upper middle-income status (P = 0.04), but there was no significant association with the population size (P = 0.395). CONCLUSION: despite increasing numbers of older people and the increasing burden of chronic disease there are few geriatricians in Africa. Without undergraduate training, even general medical physicians will have limited knowledge of specialist geriatric needs. This is an area that will require development and investment in the future.