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.

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.

A locus at 19q13.31 significantly reduces the ApoE ε4 risk for Alzheimer's Disease in African Ancestry.

African descent populations have a lower Alzheimer disease risk from ApoE ε4 compared to other populations. Ancestry analysis showed that the difference in risk between African and European populations lies in the ancestral genomic background surrounding the ApoE locus (local ancestry). Identifying the mechanism(s) of this protection could lead to greater insight into the etiology of Alzheimer disease and more personalized therapeutic intervention. Our objective is to follow up the local ancestry finding and identify the genetic variants that drive this risk difference and result in a lower risk for developing Alzheimer disease in African ancestry populations. We performed association analyses using a logistic regression model with the ApoE ε4 allele as an interaction term and adjusted for genome-wide ancestry, age, and sex. Discovery analysis included imputed SNP data of 1,850 Alzheimer disease and 4,331 cognitively intact African American individuals. We performed replication analyses on 63 whole genome sequenced Alzheimer disease and 648 cognitively intact Ibadan individuals. Additionally, we reproduced results using whole-genome sequencing of 273 Alzheimer disease and 275 cognitively intact admixed Puerto Rican individuals. A further comparison was done with SNP imputation from an additional 8,463 Alzheimer disease and 11,365 cognitively intact non-Hispanic White individuals. We identified a significant interaction between the ApoE ε4 allele and the SNP rs10423769_A allele, (ß = -0.54,SE = 0.12,p-value = 7.50x10-6) in the discovery data set, and replicated this finding in Ibadan (ß = -1.32,SE = 0.52,p-value = 1.15x10-2) and Puerto Rican (ß = -1.27,SE = 0.64,p-value = 4.91x10-2) individuals. The non-Hispanic Whites analyses showed an interaction trending in the "protective" direction but failing to pass a 0.05 significance threshold (ß = -1.51,SE = 0.84,p-value = 7.26x10-2). The presence of the rs10423769_A allele reduces the odds ratio for Alzheimer disease risk from 7.2 for ApoE ε4/ε4 carriers lacking the A allele to 2.1 for ApoE ε4/ε4 carriers with at least one A allele. This locus is located approximately 2 mB upstream of the ApoE locus, in a large cluster of pregnancy specific beta-1 glycoproteins on chromosome 19 and lies within a long noncoding RNA, ENSG00000282943. This study identified a new African-ancestry specific locus that reduces the risk effect of ApoE ε4 for developing Alzheimer disease. The mechanism of the interaction with ApoEε4 is not known but suggests a novel mechanism for reducing the risk for ε4 carriers opening the possibility for potential ancestry-specific therapeutic intervention.

Mild anxiety and depression disorders: Unusual reactions to COVID-19 lockdown in caregivers of older adults attending a psychogeriatric clinic in Southwest Nigeria.

BACKGROUND: Many sub-Saharan African countries have fragile healthcare systems and the mental health care of older adults is in a precarious state. The lockdown that accompanied COVID-19 infection was another monumental event. OBJECTIVE: This study examined the effect of the restriction and lockdown on the mental health of the caregivers of older patients attending a psychogeriatric clinic in Ibadan, Nigeria. MATERIALS AND METHODS: We selected 178 dyads of patients and their caregivers. These caregivers were administered a semi-structured questionnaire that collected demographic information and asked questions on effect of COVID-19 on caregiving. In addition, Patient Health Questionnaire-9 and generalised anxiety disorder-7 item scale were administered. Participants were interviewed through telephone. RESULTS: One hundred and seventy-eight patients' caregivers' dyads were interviewed. About 62.4% of the caregivers were children of the patients. More importantly, 97.2% and 93.8% had neither depressive nor anxiety symptoms and the caregivers expressed little worry about COVID-19. There was no significant difference in the mean depressive and anxiety scores in caregivers of patients with and without dementia (F = 0.28, P = 0.60). Caregivers who were lesser than 50 years in age had significantly higher mean score compared with those who were 50 years and above (F = 5.54, P = 0.03). CONCLUSION: The rate of anxiety and depressive symptoms was very low in this cohort as the lockdown during the pandemic produced little distress to caregivers including those caring for patients with dementia and cognitive impairment. This is a deviation from reports of some other countries and cultures which described psychological implications of COVID-19 on caregivers as severe.

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.

New Onset Poststroke Dementia at one Year in Africans.

BACKGROUND: There is limited information on new onset poststroke dementia (NPSD) in sub-Saharan Africa (SSA). We estimated incidence, cumulative incidence, risk factors and outcome of NPSD at 1 year in Nigerian survivors of a first-ever stroke. METHODS: Hospital-based prospective observational study. Assessments for global cognition, learning, memory, executive and activities of daily life (ADL) functioning were conducted at 3 poststroke timepoints (Baseline, 3- and 12 months). NPSD was ascertained according to the "National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria." Outcomes were assessed using the modified Rankin Scale (mRS), center for epidemiologic studies depression scale (CES-D 10), health related quality of life in stroke patients (HRQOLISP-26) and caregivers strain index (CSI). RESULTS: Among 144 stroke survivors who were free of dementia at baseline, we found a 1-year cumulative incidence of 4.52% (95% C.I = 3.20, 6.39). In multivariate Cox regression analyses, diabetes was associated with NPSD (Hazard Ratio = 2.10, 95% CI = 1.02, 4.35). NPSD at 3 months was independently associated with motor decline [Mean difference (MD) in mRS = 1.6, 95% C.I = 0.9, 2.3)], depression (MD in CES-D = 2.9, 95% C.I = 0.3, 5.4), caregivers burden (MD in CSI = 1.2, 95% C.I = 0.5, 1.8), and poor quality of life (MD in HRQOLISP-26 = -11.2, 95% C.I = -15.7, -6.8) at 1 year. CONCLUSION: Approximately 4.5% of stroke survivors in Nigeria had NPSD at 1 year. Diabetes, which can be prevented, represent a primary prevention target for NPSD and its consequences in SSA.

Prestroke cognitive decline in africans: Prevalence, predictors and association with poststroke dementia.

OBJECTIVES: Pre-existing cognitive decline is a risk factor for stroke onset and poststroke dementia. There is a knowledge gap on prestroke cognitive decline in indigenous Africans. We estimated prevalence and predictors of prestroke cognitive decline, as well as its association with poststroke dementia at one year in Nigerian survivors of a first ever stroke. METHODS: Prospective observational study. Prestroke cognitive decline was ascertained using an average score > 3.31 on the 16-item Informant Questionnaire for Cognitive Decline in the Elderly (IQ-CODE). Poststroke dementia was ascertained according to the 'National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria'. Associations were investigated using multivariate logistic regression models and presented as odds ratios (O.R) within 95% confidence intervals (C.I). RESULTS: Among 150 stroke survivors, prestroke cognitive decline was found in 25 (16.7%, 95% C.I = 11.5%-23.6%). In analyses adjusting for the effect of age, education and stroke severity, prestroke cognitive decline was associated with diabetes mellitus (O.R = 3.0, 95% C.I = 1.2-7.6). Ten (62.5%) survivors in the prestroke cognitive decline sub-sample developed dementia at one-year poststroke. In analyses adjusting for the effects of age, education, stroke severity and comorbid diabetes mellitus, survivors with prestroke cognitive decline had six times the odds of dementia at one year poststroke (O.R = 6.2, 95% C.I = 1.3-30.4). CONCLUSION: Prestroke cognitive decline is common, assessment is feasible and identifying pre-stroke problems has prognostic implications.

Cognitive decline before and after a first-ever stroke in Africans.

OBJECTIVES: There is a knowledge gap on the impact of pre-existing cognitive decline on poststroke decline in indigenous Africans. We describe the trajectories of domain-specific cognitive and activities of daily life (ADL) functioning across the first year of stroke in Nigerians with pre-existing cognitive decline. MATERIALS AND METHODS: Prospective observational study. Prestroke cognitive decline was ascertained retrospectively using the 16-item Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE). Assessments for global cognition, learning, memory, executive and ADL functioning were conducted at 3 time points using the Mini-Mental state examination (MMSE), 10-words list learning and delayed recall test (10 WDRT), Animal naming test and Barthel index, respectively. RESULTS: Among 150 stroke survivors, prestroke cognitive decline was found in 25 (16.7%, 95% C.I = 11.5%-23.6%). In linear regression analyses adjusting for the effect of age, education, stroke severity and comorbid diabetes mellitus, prestroke cognitive decline predicted poor memory scores at one year [Adjusted standardized mean difference (SMD) = -0.6, 95% C.I = -1.1, -0.1, p = 0.016)]. The association of prestroke cognitive decline with poststroke poor memory was substantially mediated by age (SMD = -0.9, 95% C.I = -1.4, -0.4, p < 0.001). CONCLUSION: Pre-existing cognitive decline in this sample was associated with an age-mediated poor memory function at one-year poststroke. Early institution of targeted cognitive rehabilitation in stroke survivors with pre-existing cognitive decline may reduce the neurocognitive burden of stroke in Black Africans.

The Independent Association of Prestroke Psychiatric Symptoms and Acute Phase Delirium with Poststroke Mortality at One Year in Nigeria.

BACKGROUND: Undetected acute phase delirium contributes to high poststroke mortality in sub-Saharan Africa (SSA). The present study adds to existing literature by examining the association of prestroke psychiatric symptoms with poststroke mortality at 3 and 12 months in Nigeria. METHODS: A prospective observational study with repeated delirium assessments conducted using the Confusion Assessment Method (CAM). Delirium was characterised in participants meeting criteria in the Fifth edition of the Diagnostic and Statistical Manual of mental disorders (DSM-V) as well as in those with ≥two core delirium features. Prestroke psychiatric symptoms were ascertained using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Information on mortality was obtained by research supervisors during medical follow-up. Associations were investigated using multivariate logistic regression analyses and presented as odds ratios (O.R) within 95% confidence intervals (C.I). RESULTS: Forty-five (30%) of 150 participants who provided data in the first week of stroke died by one-year follow-up. Those who died were more likely to have had a prestroke psychiatric symptom (64.4%, p=0.005) and delirium in the acute phase (60.0%, p=0.002). In analyses adjusting for the effect of age, education, tobacco smoking and stroke severity, prestroke psychiatric symptoms (O.R=3.3, 95% C.I=1.3,8.2; O.R=2.2, 95% C.I=1.0,4.6) and acute phase delirium (O.R=3.1, 95% C.I= 1.2,7.6; O.R=3.4, 95% C.I=1.5, 7.6) predicted mortality at 3 and 12 months poststroke, respectively. CONCLUSION: This study found that prestroke psychiatric symptoms and acute phase delirium independently predicted post-stroke mortality at 3- and 12 months. Detection and treatment of mental health conditions in the population at increased risk of stroke may help reduce poststroke mortality in SSA.

Cognitive, Functional, and Mortality Outcomes of Attenuated Delirium Syndrome in Stroke Survivors.

OBJECTIVES: There is a knowledge gap on the prognostic significance of subsyndromes of delirium. We describe the association of poststroke attenuated delirium syndrome (ADS) with cognitive, functional, and mortality outcomes at 3 months. METHODS: A longitudinal observational study in which repeated assessments for delirium symptoms were conducted in the first week of stroke using the confusion assessment method. Attenuated delirium syndrome was characterized in survivors who were free of the full delirium syndrome but had ≥2 core features of delirium. Baseline and follow-up assessments were conducted using the Mini-Mental State Examination (MMSE), 10-word list learning and delayed recall test, Animal naming test, and Barthel index. RESULTS: Among 150 participants recruited consecutively over 2 years, ADS was present in 32 (21.3%). Of 121 who were free of the full delirium syndrome, 21 (17.4%) had died by 3 months. Those who survived were more likely to be receiving treatment for systemic hypertension (88.5%, P = .007). In analyses adjusting for the effect of age, economic status, and systemic hypertension, ADS in the first week of stroke predicted cognitive decline at 3 months ([mean difference (MD) in MMSE scores = -3.8, 95% CI = -7.0 to -0.7, P = .019]). However, ADS was not associated with greater decline in activities of daily life (MD = -0.4, 95% CI = -2.8 to 2.0) or significant odds ratio (OR) of mortality (OR = 2.3, 95% CI = 0.8-6.3). CONCLUSION: Attenuated delirium syndrome may be an important marker of cognitive impairment at 3 months poststroke. Its detection may lead to identification of stroke survivors who are likely to benefit from evidence-based preventive interventions for poststroke cognitive decline.

Prevalence, predictors, and prognoses of prestroke neuropsychiatric symptoms at 3 months poststroke.

OBJECTIVES: Prior neuropsychiatric disturbances are risk factors for stroke. There is a knowledge gap on the predictors of prestroke psychopathology, as well as their association with stroke outcomes in survivors living in low- and middle-income countries (LMICs). We estimated prevalence, predictors, and association of prestroke neuropsychiatric symptoms with poststroke depression (PSD), disability, and mortality. DESIGN: Prospective observation. SETTING: Nigeria. PARTICIPANTS: Adult ischemic and hemorrhagic stroke survivors. MEASUREMENTS: Prestroke psychopathology were ascertained using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Outcomes were assessed using validated tools, including the Centre for Epidemiologic Studies - Depression Scale (CES-D 10) and modified Rankin scale (mRS). Independent associations were investigated using regression models with Bonferroni corrections, and presented as standardized mean differences (SMD) and odds ratios (OR) within 95% confidence intervals (CI). RESULTS: Among 150 participants, prestroke neuropsychiatric symptoms were found in 78 (52%). In multivariate logistic regression analyses, prestroke sleep disturbance was associated with systemic hypertension (OR = 5.39, 95% CI = 1.70-17.08). Prestroke neuropsychiatric symptoms independently predicted worse motor disability scores (SMD = 0.92, 95% CI = 0.21-1.62) and greater odds of poststroke mortality (OR = 2.7, 95% CI = 1.1-7.0) at 3 months. However, prestroke depression was not significantly associated with PSD. CONCLUSION: Prestroke sleep disturbances was associated with systemic hypertension, a key index of high cardiovascular risk profile and stroke. The findings should energize before-the-stroke identification and prioritization of limited treatment resources in LMICs to persons with sleep symptoms who have multiple, additional, risks of stroke.

Different Cognitive and Functional Outcomes in Attenuated and Full Delirium Syndromes Among Recent Stroke Survivors.

BACKGROUND: Very little is known about the outcomes of poststroke delirium in relation to its symptom spectrum. We investigated the 3-months cognitive and functional outcomes of attenuated (ADS) and full delirium syndromes in Nigerian survivors of first ever stroke. METHODS: A prospective observational study with repeated assessments conducted in the first week of stroke using the confusion assessment method. Full delirium was diagnosed according to criteria in the fifth edition of the diagnostic and statistical manual of mental disorders (DSM-V). ADS was characterised in survivors who were free of full, but had ≥two core features of, delirium. Baseline and follow-up assessments were conducted using the Mini-Mental state examination (MMSE), 10-words list learning and delayed recall test, Animal naming test and Barthel index. RESULTS: Among 150 participants, ADS was present in 32 (21.3%), full delirium in 29 (19.3%). In linear regression analyses adjusting for age, economic status and systemic hypertension, ADS [(Mean difference (MD) = -3.8, 95% C.I = -7.0, -0.7)] and full delirium (MD = -5.6, 95% C.I = -9.0, -2.1) independently predicted poorer global cognitive functioning at follow-up. Significant declines in memory (MD = -1.9, 95% C.I = -2.8, 0.9), executive (MD = -2.2, 95% C.I = -4.1, -0.3) and physical functioning (MD = -2.8, 95% C.I = -5.5, -0.2), as well as a 4-fold increase in the independent odds (O.R) for dementia (O.R = 4.1, 95% C.I = 1.0,16.1) were also recorded in full, but not attenuated, delirium. CONCLUSION: Attenuated and full delirium are associated with graded risk of poststroke cognitive decline. Reconsideration of poststroke delirium as a spectrum, rather than threshold-based categorical diagnosis will improve detection and prioritization of stroke survivors at increased risk of cognitive decline.

How valuable are ecopsychosocial interventions in prevention and treatment of dementia?

Dementia is a disorder that arouses major public health interest and concern. It has been projected that there will be a global increase in the number of people affected from about 46.8million in 2018 to 131million by 2050; global cost of care for 2015 was put at US$818 billion (Prince et al., 2015). Consequently, such development will lead to tremendous social and financial cost on family and society. Currently, there is no cure for dementia and that has led to increased research activities on prevention strategies, which often has to start with a number of midlife activities. These include regular exercise, diet, treatment of cardiovascular risk factors, and social and educational stimulation through life.

Low education and lack of spousal relationship are associated with dementia in older adults with diabetes mellitus in Nigeria.

BACKGROUND: The relationship between dementia and type 2 diabetes mellitus (T2DM) in older adults is well established in the literature. However, there have been few studies on this relationship in older adults living in low- and middle-income countries, and most demographic projections predict that older adult population will increase substantially in these regions by 2050. METHODS: In this study, older adults with T2DM attending a tertiary health facility were examined and compared with community-dwelling older adults without T2DM. The participants were assessed using the Consortium to Establish Registry for Alzheimer's Disease, the Stick Design Test, the 30-item Geriatric Depression Scale, and the Instrumental Activities of Daily Living Scale. Additionally, all the participants had a physical examination, including assessment of glycated haemoglobin, fasting blood glucose, lipid profile, and HIV status. A consensus diagnosis of dementia was made based on the criteria for dementia in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the International Classification for Diseases, 10th edition. The data were analyzed using SPSS version 20 for Windows. RESULTS: This study included 224 diabetic patients and 116 controls. A total of 27 diabetic patients (12.1%) had dementia, 19 of whom were women. Of the 27 diabetic patients with dementia, 25 patients (92.6%) had Alzheimer's disease and 2 patients (7.4%) had mixed dementia (vascular dementia and Alzheimer's disease). Only one person among the controls had Alzheimer's type dementia. Dementia in the diabetic patients was significantly associated with advancing age, female gender, education level, duration of diabetes, and absence of a spouse. CONCLUSION: Dementia is common in older adults with T2DM in this low-resource setting, and the risk factors for dementia were similar to those reported in earlier studies in Western societies.

Stroke severity predicts poststroke delirium and its association with dementia: Longitudinal observation from a low income setting.

OBJECTIVE: The effect of delirium on stroke outcome has not been quantified in sub-Saharan Africa. We investigated the prevalence of delirium occurring within one week of stroke in Nigerian survivors and its association with dementia and mortality at 3months. METHODS: Delirium was ascertained after repeated assessments within one week of stroke using the Confusion Assessment Method. Demographic and clinical characteristics, stroke severity, current and pre-morbid cognitive functioning were also assessed. Participants were then followed up for 3months using culturally-validated neuropsychological tools. Probable dementia was ascertained according to the National Institute of Neurological Disorders and Stroke (NINDS-AIREN) criteria. Associations were investigated using both binomial and multinomial logistic regression analyses and presented as odds ratios (O.R) and relative risk ratios (RRR). RESULTS: Of 101 consenting stroke survivors, 99 had two assessments for delirium within one week of the stroke. Delirium was present in 33.3% of stroke survivors (65.6% hypoactive, 21.9% hyperactive, and 12.1% mixed type). Having a severe stroke was associated with delirium (O.R=6.2, 95% C.I=1.1-13.8) after adjusting for age, gender, education and economic status, lifestyle factors, multimorbidities and laterality. At follow-up, those with severe stroke had a stronger association between delirium and dementia (RRR=4.3, 95% C.I=1.2-15.6) or death (RRR=3.7, 95% C.I=1.1-12.1). CONCLUSION: Delirium, in this sub-Saharan African sample, was already present in about one-third of survivors within one week of stroke. Survivors of severe stroke are at higher risk of delirium and its complications, and could be important target for delirium preventive interventions.

Prevalence of HIV-Associated Neurocognitive Disorder (HAND) among Patients Attending a Tertiary Health Facility in Northern Nigeria.

BACKGROUND: HIV-associated neurocognitive disorder (HAND) is a great source of morbidity in sub-Saharan African region. However, the magnitude of this problem remains largely uninvestigated despite having the largest number of population with HIV/AIDS. The aim of this study is to determine the prevalence of HAND among patients attending a tertiary health facility in Nigeria. METHOD: We conducted a cross-sectional study among HIV-positive patients on antiretroviral therapy (ART) for at least 1 year. They were assessed using the International HIV Dementia Scale, Word Recall Test, Stick Design Test, Subjective Cognitive Complaint Questionnaire, Alcohol Use Disorder Identification Test, Drug Abuse Screening Test, Center for Epidemiological Study-Depression Scale, Instrumental Activity of Daily Living, and neurological examination. The CD4 count and viral load were determined for all the participants. A consensus diagnosis was made on each case based on the Frascati criteria. Data obtained were analyzed using "SPSS" for Windows version 15. RESULTS: A total of 418 HIV-positive patients participated in the study, of which 325 (77.8%) are females. The mean age (standard deviation) of the participants was 37.2 (9.3) years. The prevalence of HAND was 21.5% (95% confidence interval [CI] = 17.6%-25.4%), of which 9.6% were asymptomatic. The significant predictors of HAND in this study are duration of illness (odds ratio [OR] = 1.33 P < .001), detectable viral load (OR = 0.19, P < .001), CD4 count (OR = 0.99, P < .001), education (OR = 0.94, P = .011), stopping medication (OR = 3.55 P = .01), and severity of illness (OR = 1.24, P = .005). CONCLUSION: One-fifth of the HIV-positive patients in this study had HAND. Various sociodemographic and clinical features were related to the prevalence of HAND.

Dementia incidence declined in African-Americans but not in Yoruba.

INTRODUCTION: To compare dementia incidence of African-American and Yoruba cohorts aged ≥70 years enrolled in 1992 and 2001. METHODS: African-Americans residing in Indianapolis and Yoruba in Ibadan, Nigeria without dementia were enrolled in 1992 and 2001 and evaluated every 2-3 years until 2009. The cohorts consist of 1440 African-Americans, 1774 Yoruba in 1992 and 1835 African-Americans and 1895 Yoruba in the 2001 cohorts aged ≥70 years. RESULTS: In African-Americans, dementia and Alzheimer's disease (AD) incidence rates were significantly lower in 2001 than 1992 for all age groups except the oldest group. The overall standardized annual dementia incidence rates were 3.6% (95% confidence interval [CI], 3.2%-4.1%) in the 1992 cohort and 1.4% (95% CI, 1.2%-1.7%) in the 2001 cohort. There was no significant difference in dementia or AD incidence between the Yoruba cohorts. DISCUSSION: Future research is needed to explore the reasons for the differential changes in incidence rates in these two populations.

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.

Psychiatric disorders and adherence to antiretroviral therapy among a population of HIV-infected adults in Nigeria.

Psychiatric disorders are common among people living with HIV in Nigeria. Adherence is necessary to optimise the outcome of antiretroviral therapy. In this study, we aimed to identify associations between antiretroviral adherence, measured by one-week and one-month self-reported missed doses, and psychiatric illness in a cohort previously assessed for psychiatric disorders using the Composite International Diagnostic Interview. The study participants comprised 151 adults with major depression, anxiety or suicidal symptoms, and 302 matched-control participants. Two controls were randomly selected for each case within the same gender and education level. We compared participants with psychiatric disorders (WPDs) and no psychiatric disorders (NPDs) on selected demographic and clinical variables, in addition to adherence. Participants with one or more missed doses in the preceding month had twice the odds of having a major depressive episode as those with no missed doses during this period (OR 2.22, 95% CI 1.03, 4.79). This association remained significant after adjusting for selected risk factors. There was no statistically significant difference between WPD and NPD groups on either one-week or one-month adherence, or on age, marital status, occupational class, HIV viral load at enrolment or current CD4 cell count. Among Nigerian adults with HIV, suboptimal antiretroviral adherence is associated with, and could be a sign of, depression. Routine self-report adherence assessments may potentially be utilised in identifying individuals at risk among this population.