Integrated Primary Palliative Care in Nigeria- Perspectives of Patients, Families and Providers.

BACKGROUND: Palliative care should be integrated into primary healthcare systems within low- and middle-income countries to achieve Universal Health Coverage goals. We aimed to identify preferences and expectations for primary palliative care among people living with serious illness and their families and the readiness of primary healthcare providers to deliver primary palliative care in Nigeria. METHODS: Qualitative descriptive interview study with 48 participants: people living with serious illness (n=21) and their family caregivers (n=15), healthcare providers (n=12). Data were analysed using thematic analysis. RESULTS: Three major themes were identified. 1.) Engaging patients and families. 2.) Managing patients and families' expectations and preferences. 3.) Addressing staffing-related issues. Patients and families have existing trust and bonds from using primary healthcare but lack individual agency necessary for person-centered care decisions. They expect an easily accessible service, opportunities for social interaction and adequate communication. Development of healthcare providers is needed to ensure an appropriate clinical response, manage interprofessional trust and ensure clear role delineation. CONCLUSIONS: Our findings have identified specific approaches to implement the WHO policy on integrated primary palliative care. Palliative care integration within primary healthcare in Nigeria can be achieved through building information and communication skills of healthcare providers, engaging and empowering patients to exercise their agency in care decisions, and adequately delineating healthcare providers' roles to ensure staff work within their competencies and training.

Population normative data for three cognitive screening tools for older adults in sub-Saharan Africa / Dados normativos populacionais para três instrumentos de triagem cognitiva para idosos na áfrica subsaariana

ABSTRACT In sub-Saharan Africa (SSA),cognitive screening is complicated by both cultural and educational factors, and the existing normative values may not be applicable. The Identification of Dementia in Elderly Africans (IDEA) cognitive screen is a low-literacy measure with good diagnostic accuracy for dementia. Objective: The aim of this study is to report normative values for IDEA and other simple measures [i.e., categorical verbal fluency, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) 10-word list] in representative community-dwelling older adults in SSA. Methods: Individuals aged ≥60 years resident in 12 representative villages in Kilimanjaro, Tanzania and individuals aged ≥65 years resident within three communities in Akinyele Local Government Area, Oyo State, Nigeria underwent cognitive screening. The normative data were generated by the categories of age, sex, and education. Results: A total of 3,011 people in Tanzania (i.e., 57.3% females and 26.4% uneducated) and 1,117 in Nigeria (i.e., 60.3% females and 64.5% uneducated) were screened. Individuals with higher age, lower education, and female gender obtained lower scores. The 50th decile values for IDEA were 13 (60-64 years) vs. 8/9 (above 85 years), 10-11 uneducated vs. 13 primary educated, and 11/12 in females vs. 13 in males. The normative values for 10-word list delayed recall and categorical verbal fluency varied with education [i.e., delayed recall mean 2.8 [standard deviation (SD) 1.7] uneducated vs. 4.2 (SD 1.2) secondary educated; verbal fluency mean 9.2 (SD 4.8) uneducated vs. 12.2 (SD 4.3) secondary educated], substantially lower than published high-income country values. Conclusions: The cut-off values for commonly used cognitive screening items should be adjusted to suit local normative values, particularly where there are lower levels of education.

RESUMO Na África Subsaariana (ASS), a triagem cognitiva é complicada por fatores culturais e educacionais, além dos valores normativos existentes poderem não ser aplicáveis. O rastreio cognitivo Identification of Dementia in Elderly Africans (IDEA) é uma medida para níveis baixos de alfabetização com boa acurácia diagnóstica para demência. Objetivo: Relatar os valores normativos para a IDEA e outras medidas simples (fluência verbal categórica, a lista de 10 palavras do Consortium to Establish a Registry for Alzheimer's Disease (CERAD) em idosos residentes na comunidade, representativos da ASS. Métodos: Indivíduos com idade ≥60 residentes em 12 comunidades representativas em Kilimanjaro, Tanzânia e indivíduos com idade ≥65 anos residentes em três comunidades na área governamental de Akinyele, Estado de Oyo, Nigéria, foram submetidos à triagem cognitiva. Os dados normativos foram gerados por faixas etárias, sexo e escolaridade. Resultados: Um total de 3.011 pessoas na Tanzânia (57,3% mulheres, 26,4% sem educação) e 1.117 na Nigéria (60,3% mulheres, 64,5% sem educação) foram examinadas. Os indivíduos com idade mais alta, menor escolaridade e mulheres obtiveram escores mais baixos. Os valores do percentil 50 para a IDEA foram 13 (60-64 anos) vs. 8/9 (85+ anos), 10-11 para analfabetos vs. 13 com educação primária e 11/12 em mulheres vs. 13 em homens. Os valores normativos para a evocação tardia da lista de 10 palavras e a fluência verbal categórica variaram com a educação (evocação tardia 2,8 (SD 1,7) para os sem educação, vs. 4,2 (SD 1,2) para com educação secundária; fluência verbal 9,2 (DP 4,8) para os sem educação vs. 12,2 (SD 4.3) para os com ensino médio, substancialmente inferior aos valores publicados em países de alta renda. Conclusões: Os valores de corte para testes de triagem cognitiva comumente usados devem ser ajustados para se adequar aos valores normativos locais, particularmente em níveis baixos de educação.

Polycystic ovarian syndrome in Nigerian women with epilepsy on carbamazepine/levetiracetam monotherapy.

OBJECTIVE: The study is aimed at comparing effects of older drugs like carbamazepine (CBZ) and newer agent like levetiracetam (LEV) on polycystic ovarian syndrome (PCOS) in women with epilepsy (WWE). METHODS: An interviewer-based questionnaire was used to obtain relevant clinical information from 50 WWE on CBZ and LEV monotherapy, respectively, and 50 age-matched controls. The diagnosis of epilepsy was clinical with electroencephalographic features taken into consideration and the seizures classified using the 2017 International League Against Epilepsy classification. The diagnosis of PCOS was based on the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. RESULTS: The frequency of PCOS and its subcomponent were higher among WWE compare to controls. PCOS was present in 22 (44%) of LEV group compare to 8 (16%) CBZ group. The frequency of its subcomponent was higher among those on LEV except for comparable effect with regard to oligomenorrhea. The levels of the sex steroid hormone were comparable in both groups of WWE except luteal phase luteinizing hormone, which was lower among the LEV group (P .001). The follicular phase estradiol level was lower (P .021), and follicle-stimulating hormone level was about 2-fold higher (P .03) among WWE compare to controls. The mean value testosterone was significantly lower among controls compared to WWE. CONCLUSIONS: The increased frequency of PCOS and its subcomponent and the unsatisfactory effect of LEV compared to CBZ on reproductive endocrine function underscore the need for routine reproductive endocrine evaluation to improve overall quality of life.

HIV-1 Central Nervous System Compartmentalization and Cytokine Interplay in Non-Subtype B HIV-1 Infections in Nigeria and Malawi.

HIV-1 compartmentalization in the central nervous system (CNS) and its contribution to neurological disease have been well documented. Previous studies were conducted among people infected with subtypes B or C where CNS compartmentalization has been observed when comparing viral sequences in the blood to virus in cerebrospinal fluid (CSF). However, little is known about CNS compartmentalization in other HIV-1 subtypes. Using a deep sequencing approach with Primer ID, we conducted a cross-sectional study among Nigerian and Malawian HIV-1 cohorts with or without fungal Cryptococcus infection diagnosed as cryptococcal meningitis (CM) to determine the extent of CSF/CNS compartmentalization with CM. Paired plasma and CSF samples from 45 participants were also analyzed for cytokine/chemokine levels. Viral populations comparing virus in the blood and the CSF ranged from compartmentalized to equilibrated, including minor or partial compartmentalization or clonal amplification of a single viral sequence. The frequency of compartmentalized viral populations in the blood and CSF was similar between the CM- and CM+ participants. We confirmed the potential to see compartmentalization with subtype C infection and have also documented CNS compartmentalization of an HIV-1 subtype G infection. Cytokine profiles indicated a proinflammatory environment, especially within the CSF/CNS. However, sCD163 was suppressed in the CSF in the presence of CM, perhaps due to elevated levels of IL-4, which were also a feature of the cytokine profile, showing a distinct cytokine profile with CM.

Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups.

OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.

Rapid HIV Antigen-Antibody Assays and Detection of Acute HIV Infection in Sub-Saharan Africa.

Detection of acute HIV infection is a unique problem that fourth-generation HIV assays were expected to alleviate. In this commentary, we draw attention to the limitations and challenges with use of currently available rapid antigen-antibody (Ag/Ab) combination tests for detection of acute HIV infection in sub-Saharan Africa. Laboratory-based HIV-1 Ag/Ab immunoassays are complex, requiring specialized equipment and handling that are currently not affordable in many settings in Africa. The point-of-care Ag/Ab platform on the other hand is easier to deploy and potentially more accessible in resource-limited settings. However, available fourth-generation HIV-1 rapid diagnostic tests have demonstrated poor performance characteristics in field studies where non-B subtypes of HIV-1 dominate. The potential for point-of-care HIV-1 Ag/Ab diagnostics to significantly improve detection of acute HIV infection remains yet to be realized in sub-Saharan Africa. Assay platforms need to be optimized to identify local circulating subtypes, and optimal algorithms need to be determined.

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke.

BACKGROUND: Annotation and Image Markup on ClearCanvas Enriched Stroke-phenotyping Software (ACCESS) is a novel stand-alone computer software application that allows the creation of simple standardized annotations for reporting brain images of all stroke types. We developed the ACCESS application and determined its inter-rater and intra-rater reliability in the Stroke Investigative Research and Educational Network (SIREN) study to assess its suitability for multicenter studies. METHODS: One hundred randomly selected stroke imaging reports from 5 SIREN sites were re-evaluated by 4 trained independent raters to determine the inter-rater reliability of the ACCESS (version 12.0) software for stroke phenotyping. To determine intra-rater reliability, 6 raters reviewed the same cases previously reported by them after a month of interval. Ischemic stroke was classified using the Oxfordshire Community Stroke Project (OCSP), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and Atherosclerosis, Small-vessel disease, Cardiac source, Other cause (ASCO) protocols, while hemorrhagic stroke was classified using the Structural lesion, Medication, Amyloid angiopathy, Systemic disease, Hypertensive angiopathy and Undetermined (SMASH-U) protocol in ACCESS. Agreement among raters was measured with Cohen's kappa statistics. RESULTS: For primary stroke type, inter-rater agreement was .98 (95% confidence interval [CI], .94-1.00), while intra-rater agreement was 1.00 (95% CI, 1.00). For OCSP subtypes, inter-rater agreement was .97 (95% CI, .92-1.00) for the partial anterior circulation infarcts, .92 (95% CI, .76-1.00) for the total anterior circulation infarcts, and excellent for both lacunar infarcts and posterior circulation infarcts. Intra-rater agreement was .97 (.90-1.00), while inter-rater agreement was .93 (95% CI, .84-1.00) for TOAST subtypes. Inter-rater agreement ranged between .78 (cardioembolic) and .91 (large artery atherosclerotic) for ASCO subtypes and was .80 (95% CI, .56-1.00) for SMASH-U subtypes. CONCLUSION: The ACCESS application facilitates a concordant and reproducible classification of stroke subtypes by multiple investigators, making it suitable for clinical use and multicenter research.

Interleukin-6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men.

BACKGROUND: Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub - Saharan African populations. Interleukin-6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. AIM: Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6, CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. METHODS: Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of the 23 SNPs in rigorously phenotyped cases (N=429) of ischemic stroke (Men=198; Women=231) and stroke- free (N=483) controls (Men=236; Women=247). RESULTS: Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans=8.6%) was significantly associated with ischemic stroke in men (OR=2.006, 95% CI=[1.065, 3.777], p=0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans=1.7%) was also associated with ischemic stroke in men (OR=2.550, 95% CI=[1.027, 6.331], p=0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke. CONCLUSION: Polymorphisms rs1800796 in IL6 gene and rs2383207 in CDKN2A/CDKN2B gene have significant associations with ischemic stroke in indigenous West African men. CDKN2A/CDKN2B SNP rs2383207 is independently associated with ischemic stroke in indigenous West African men. Further research should focus on the contributions of inflammatory genes and other genetic polymorphisms, as well as the influence of sex on the neurobiology of stroke in people of African ancestry.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.

BACKGROUND: Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. METHODS: We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. FINDINGS: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). INTERPRETATION: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.

Cognitive Impairment Among the Aging Population in a Community in Southwest Nigeria.

BACKGROUND: Vascular risk models can be quite informative in assisting the clinician to make a prediction of an individual's risk of cognitive impairment. Thus, a simple marker is a priority for low-capacity settings. This study examines the association of selected simple to deploy vascular markers with cognitive impairment in an elderly population. METHOD: This cross-sectional study assessed the cognitive functions of older persons 65 years and older in southwest Nigeria. Vascular parameters and risk factors were also measured. Analysis was done using SPSS, and logistic regression was used to explore the association between cognitive impairment and certain vascular risk factors such as elevated blood pressure, diabetes, and pulse pressure. RESULTS: The study population comprised 623 participants (29.1% men) with mean age 73 ± 8.9 years. Having mean arterial pressure (MAP) and pulse pressure in the fourth quartiles (27% and 29.9%, respectively) was significantly associated with cognitive impairment (p= .001,p< .001). Predicted cardiovascular risks of 10% or more was significantly associated with cognitive impairment (p< .001). After adjusting for age, gender, educational level, and years of smoking, those with MAP in the fourth quartile were up to 3 times more likely to have cognitive impairment compared to those within the first quartile. CONCLUSION: Our study demonstrated that among elderly Nigerians, MAPs of 114 mmHg and more was an independent predictor of cognitive impairment. This is a simple measure that is available in low-capacity areas.

Community validation of the IDEA study cognitive screen in rural Tanzania.

OBJECTIVES: The dementia diagnosis gap in sub-Saharan Africa (SSA) is large, partly because of difficulties in screening for cognitive impairment in the community. As part of the Identification and Intervention for Dementia in Elderly Africans (IDEA) study, we aimed to validate the IDEA cognitive screen in a community-based sample in rural Tanzania METHODS: Study participants were recruited from people who attended screening days held in villages within the rural Hai district of Tanzania. Criterion validity was assessed against the gold standard clinical dementia diagnosis using DSM-IV criteria. Construct validity was assessed against, age, education, sex and grip strength and instrumental activities of daily living (IADLs). Internal consistency and floor and ceiling effects were also examined. RESULTS: During community screening, the IDEA cognitive screen had high criterion validity, with an area under the receiver operating characteristic curve of 0.855 (95% CI 0.794 to 0.915). Higher scores on the screen were significantly correlated with lower age, male sex, having attended school, better grip strength and improved performance in activities of daily living. Factor analysis revealed a single factor with an eigenvalue greater than one, although internal consistency was only moderate (Cronbach's alpha = 0.534). CONCLUSIONS: The IDEA cognitive screen had high criterion and construct validity and is suitable for use as a cognitive screening instrument in a community setting in SSA. Only moderate internal consistency may partly reflect the multi-domain nature of dementia as diagnosed clinically. Copyright © 2016 John Wiley & Sons, Ltd.

Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.

Plasma homocysteine, a metabolite involved in key cellular methylation processes seems to be implicated in cognitive functions and cardiovascular health with its high levels representing a potential modifiable risk factor for Alzheimer's disease (AD) and other dementias. A better understanding of the genetic factors regulating homocysteine levels, particularly in non-white populations, may help in risk stratification analyses of existing clinical trials and may point to novel targets for homocysteine-lowering therapy. To identify genetic influences on plasma homocysteine levels in individuals with African ancestry, we performed a targeted gene and pathway-based analysis using a priori biological information and then to identify new association performed a genome-wide association study. All analyses used combined data from the African American and Yoruba cohorts from the Indianapolis-Ibadan Dementia Project. Targeted analyses demonstrated significant associations of homocysteine and variants within the CBS (Cystathionine beta-Synthase) gene. We identified a novel genome-wide significant association of the AD risk gene CD2AP (CD2-associated protein) with plasma homocysteine levels in both cohorts. Minor allele (T) carriers of identified CD2AP variant (rs6940729) exhibited decreased homocysteine level. Pathway enrichment analysis identified several interesting pathways including the GABA receptor activation pathway. This is noteworthy given the known antagonistic effect of homocysteine on GABA receptors. These findings identify several new targets warranting further investigation in relation to the role of homocysteine in neurodegeneration.

Validation of the Identification and Intervention for Dementia in Elderly Africans (IDEA) cognitive screen in Nigeria and Tanzania.

BACKGROUND: We have previously described the development of the Identification and Intervention for Dementia in Elderly Africans (IDEA) cognitive screen for use in populations with low levels of formal education. The IDEA cognitive screen was developed and field-tested in an elderly, community-based population in rural Tanzania with a relatively high prevalence of cognitive impairment. The aim of this study was to validate the IDEA cognitive screen as an assessment of major cognitive impairment in hospital settings in Nigeria and Tanzania. METHODS: In Nigeria, 121 consecutive elderly medical clinic outpatients reviewed at the University College Hospital, Ibadan were screened using the IDEA cognitive screen. In Tanzania, 97 consecutive inpatients admitted to Mawenzi Regional Hospital (MRH), Moshi, and 108 consecutive medical clinic outpatients attending the geriatric medicine clinic at MRH were screened. Inter-rater reliability was assessed in Tanzanian outpatients attending St Joseph's Hospital in Moshi using three raters. A diagnosis of dementia or delirium (DSM-IV criteria) was classified as major cognitive impairment and was provided independently by a physician blinded to the results of the screening assessment. RESULTS: The area under the receiver operating characteristic (AUROC) curve in Nigerian outpatients, Tanzanian outpatients and Tanzanian inpatients was 0.990, 0.919 and 0.917 respectively. Inter-rater reliability was good (intra-class correlation coefficient 0.742 to 0.791). In regression models, the cognitive screen did not appear to be educationally biased. CONCLUSIONS: The IDEA cognitive screen performed well in these populations and should prove useful in screening for dementia and delirium in other areas of sub-Saharan Africa.

Obesity and 10-year mortality in very old African Americans and Yoruba-Nigerians: exploring the obesity paradox.

BACKGROUND: To compare the effect of obesity and related risk factors on 10-year mortality in two cohorts of older adults of African descent; one from the United States and one from Nigeria. METHODS: Study participants were community residents aged 70 or older of African descent living in Indianapolis, Indiana (N = 1,269) or Ibadan, Nigeria (1,197). We compared survival curves between the two cohorts by obesity class and estimated the effect of obesity class on mortality in Cox proportional hazards models controlling for age, gender, alcohol use, and smoking history, and the cardiometabolic biomarkers blood pressure, triglycerides, high-density lipoprotein, low-density lipoprotein, and C-reactive protein. RESULTS: We found that underweight was associated with an increased risk of death in both the Yoruba (hazards ratio = 1.35, 95% confidence interval: 1.12-1.63) and African American samples (hazards ratio = 2.49, 95% confidence interval: 1.40-4.43) compared with those with normal weight. The overweight and obese participants in both cohorts experienced survival similar to the normal weight participants. Controlling for cardiometabolic biomarkers had little effect on the obesity-specific hazard ratios in either cohort. CONCLUSIONS: Despite significant differences across these two cohorts in terms of obesity and biomarker levels, overall 10-year survival and obesity class-specific survival were remarkably similar.

Homocysteine levels and dementia risk in Yoruba and African Americans.

BACKGROUND: High levels of homocysteine have been associated with increased risk for dementia although results have been inconsistent. There are no reported studies from the developing world including Africa. METHODS: In this longitudinal study of two community-dwelling cohorts of elderly Yoruba and African Americans, levels of homocysteine, vitamin B12 and folate were measured from blood samples taken in 2001. These levels were compared in two groups, participants who developed incident dementia in the follow-up until 2009 (59 Yoruba and 101 African Americans) and participants who were diagnosed as cognitively normal or in the good performance category at their last follow-up (760 Yoruba and 811 African Americans). Homocysteine levels were divided into quartiles for each site. RESULTS: After adjusting for age, education, possession of ApoE, smoking, and time of enrollment the higher quartiles of homocysteine were associated with a non-significant increase in dementia risk in the Yoruba (homocysteine quartile 4 vs. 1 OR: 2.19, 95% CI 0.95-5.07, p = 0.066). For the African Americans, there was a similar but non-significant relationship between higher homocysteine levels and dementia risk. There were no significant relationships between levels of vitamin B12 and folate and incident dementia in either site although folate levels were lower and vitamin B12 levers were higher in the Yoruba than in the African Americans. CONCLUSIONS: Increased homocysteine levels were associated with a similar but non-significant increase in dementia risk for both Yoruba and African Americans despite significant differences in folate levels between the two sites.

Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.

The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (F(ST) < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 × 10(-11)) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers.

Weight loss and incident dementia in elderly Yoruba Nigerians: a 10-year follow-up study.

BACKGROUND: The relationship between weight and dementia risk has not been investigated in populations with relatively low body mass index (BMI) such as the Yoruba. This study set out to achieve this objective using a prospective observational design. METHODS: The setting was Idikan Ward in Ibadan City, Nigeria. The participants were all aged 65 years or older and were enrolled in the Indianapolis-Ibadan Dementia Project. Repeated cognitive assessments and clinical evaluations were conducted to identify participants with dementia or MCI during 10 years of follow-up (mean duration: 5.97 years). BMI measures, information on alcohol, smoking history, cancer, hypertension, diabetes, heart attack, stroke and depression were collected at each follow-up evaluation. Mixed effect models adjusted for covariates were used to examine the differences in BMI among participants who developed dementia or MCI and those who remained cognitively normal during the follow-up. RESULTS: This analysis included 1559 participants who had no dementia at their first BMI measurements. There were 136 subjects with incident dementia, 255 with MCI and 1168 with normal cognition by the end of the study. The mean BMI at baseline was higher for female participants (22.31; SD = 4.39) than for male (21.09; SD = 3.61, p < 0.001). A significantly greater decline in BMI was found in those with either incident dementia (p < 0.001) or incident MCI (p < 0.001) compared to normal subjects. CONCLUSION: Decline in BMI is associated with incident MCI and dementia in elderly Yoruba. This observation calls for close monitoring of weight loss in elderly individuals which may indicate future cognitive impairment for timely detection and tailored interventions.

Chapter 50: history of tropical neurology.

Tropical neurology began less than two centuries ago. Consumption of dietary toxins predominated at the beginning and gave birth to the geographic entity. The story moved from lathyrism through Jamaican neuropathy to cassava-induced epidemic neuropathy, which was contrasted with Konzo, also associated with cassava. Other tropical diseases enumerated with chronological details include: Chaga's diseases, kwashiorkor, Madras type of motor neuron disease, atlanto-axial dislocation, Burkitt's lymphoma and Kuru, associated with cannibalism among the Fore linguistic group in New Guinea. More recent documentation includes the Cuban neuropathy in 1991 with an epidemic of visual loss and neuropathy, Anaphe venata entomophagy in Nigeria presenting as seasonal ataxia, and neurological aspects of the human immunodeficiency virus infection complete the picture. With time, professional associations were formed and the pioneers were given prominence. The World Federation of Neurology featured Geographic Neurology as a theme in 1977 and Tropical Neurology was given prominence at its 1989 meeting in New Delhi, India. The situation remains unchanged with regards to rare diseases like Meniere's, multiple sclerosis, hereditary disorders. However, with westernization and continued urbanization, changing disease patterns are being observed and tropical neurology may depart from dietary toxins to more western world-type disorders.

Prevalence rates for dementia and Alzheimer's disease in African Americans: 1992 versus 2001.

BACKGROUND: This study compares age-specific and overall prevalence rates for dementia and Alzheimer's disease (AD) in two nonoverlapping, population-based cohorts of elderly African Americans in Indianapolis in 2001 and 1992. METHODS: We used a two-stage design. The first stage involves the Community Screening Interview for Dementia (CSI-D). The CSI-D scores are grouped into good, intermediate, and poor performance before selection for clinical assessment. Diagnoses were performed using standard criteria in a consensus diagnosis conference; clinicians were blind to performance groups. In 1992, interviewers visited randomly sampled addresses to enroll self-identified African Americans aged > or =65 years. Of 2582 eligible, 2212 enrolled (9.6% refused, and 4.7% were too sick). In 2001, Medicare rolls were used for African Americans aged >70 years. Of 4260 eligible, 1892 (44%) enrolled, 1999 (47%) refused, and the remainder did not participate for other reasons. RESULTS: The overall age-adjusted prevalence rate for dementia at age > or =70 years in 2001 was 7.45% (95 confidence interval [CI], 4.27-10.64), and in the 1992 cohort, this prevalence rate was 6.75% (95% CI, 5.77-7.74). The overall age-adjusted prevalence rate at age > or =70 years for AD in the 2001 cohort was 6.77% (95% CI, 3.65-9.90), and for the 1992 cohort, it was 5.47% (95% CI, 4.51-6.42). Rates for dementia and AD were not significantly different in the two cohorts (dementia, P = .3534; AD, P = .2649). CONCLUSIONS: We found no differences in the prevalence rates of dementia and AD between 1992 and 2001, despite significant differences in medical history and medical treatment within these population-based cohorts of African American elderly.

Effect of progression of disease on cognitive performance in HIV/AIDS.

BACKGROUND: HIV infection causes a range of cognitive and behavioral symptoms that become more frequent and severe as the immune system deteriorates and symptomatic illness ensues. OBJECTIVE: To determine the impact of disease progression on cognitive abilities of Nigerian Africans who present in the HIV/AIDS clinic of the University Teaching Hospital, Benin City, Nigeria, using the CD4 levels as the measure of disease progression. METHODS: A total of 288 subjects comprising 96 randomly selected symptomatic AIDS patients, 96 randomly selected asymptomatic HIV-positive patients and 96 HIV-negative controls participated in the study. Enzyme-linked immunosorbent assay (ELISA) method was used to detect HIV infection, and CD4 levels were obtained for all subjects. The Community Screening Interview for Dementia (CSI 'D') was used to assess cognitive performance of subjects. Subjects were matched for age, sex and level of education. RESULTS: Each category of subjects comprised 48 males and 48 females. The mean ages were 32.94 +/- 8.0 years, 31.47 +/- 6.7 years and 33.56 +/- 7.1 years for the controls, asymptomoatic HIV-positive and symptomatic AIDS subjects respectively (p = 0.127). The mean CD4 levels were 684 +/- 44/microL (controls), 284 +/- 62/microL (asymptomatic HIV positive) and 142 +/- 36/microL (symptomatic AIDS). The mean CS1 'D' scores were 66.46 +/- 1.90 (controls), 66.31 +/- 2.14 (asymptomatic HIV positive) and 56.62 +/- 4.23 (symptomatic AIDS). CONCLUSION: Cognitive abilities of HIV/AIDS patients decline as the disease progresses. This is reflected in the cognitive performances of the symptomatic AIDS patients. The lower the CD4 levels, the worse the cognitive deficits. There was, however, no significant difference in the performance of asymptomatic HIV-positive patients and the controls.