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.

Decentralized clinical trials for medications to reduce the risk of dementia: Consensus report and guidance.

INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field. METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations. RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention provided adequate safety checks and balances are included. A total of 40 recommendations are presented, spanning aspects of decentralized clinical trials, including safety, dispensing, outcome assessment, and data collection. DISCUSSION: These recommendations provide an accessible, pragmatic guide for the design and conduct of remote medication trials for dementia prevention. HIGHLIGHTS: Clinical trials of medication have begun adopting decentralized approaches. Researchers in the field lack guidance on what would be appropriate circumstances and frameworks for what would be appropriate circumstances and frameworks for the use of decentralized trial methods in dementia prevention. The present report provides consensus-based expert recommendations for decentralized clinical trials for dementia 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 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.

Effects of aerobic exercise on quality of life of people with HIV-associated neurocognitive disorder on antiretroviral therapy: a randomised controlled trial.

BACKGROUND: HIV-associated neurocognitive disorder (HAND) negatively impacts quality of life (QoL) of people living with HIV who are on antiretroviral therapy (ART). Behavioural intervention adjunct to ART may improve QoL of people with HAND. We determine the effect of a 12-week aerobic exercise programme on QoL in people with HAND who were receiving ART. TRIAL DESIGN: This was a parallel-group, randomised controlled trial with concealed allocation and intention-to-treat analysis. METHODS: We identified 73 participants diagnosed with HAND. Participants were sampled from an earlier study that examined the prevalence of HAND according to the Frascati criteria. Participants were randomised and allocated to an intervention of 12-weeks of aerobic exercise, comprising three 20-60 min sessions per week of moderate-intensity aerobic exercise using a cycle ergometer. The primary outcome was QoL, which was evaluated using the World Health Quality of Life Questionnaire (WHOQoL)-BREF. RESULTS: Participants in the exercise (n = 39) and control (n = 35) groups had similar sociodemographic characteristics (p > 0.05). Following the 12-week aerobic exercise programme, participants in the exercise group had improved physical (p < 0.001), psychological (p = 0.008) and environmental (p = 0.001) domains of the QoL (p = 0.001) and overall QoL (p = 0.001) relative to the control group. Similarly, participants in the exercise group had lower depression scores than participants in the control group. Depression scores in the exercise group were still lower 3 months post-intervention (p = 0.007). Only the improvements in physical (p = 0.02) and psychological (p = 0.007) domains of QoL were sustained at 3 months post-intervention. CONCLUSIONS: Aerobic exercise improves the QoL of people with HAND. To ensure sustained benefits, people with HAND may need to engage in long-term physical exercise. Trial registration The trial is registered with the PAN African Trial Registry (PACTR). Date: 01/09/2020, ID: PACTR202009483415745.

Aerobic exercise for HIV-associated neurocognitive disorders in individuals on antiretroviral therapy: A randomised controlled trial.

INTRODUCTION: The increasing burden of self-limiting forms of HIV-associated neurocognitive disorder (HAND) in the antiretroviral therapy era calls for adjunctive interventions. The study aimed to determine the effects of a 12-week aerobic exercise programme on HAND. METHODS: This is a parallel-group, randomized controlled trial with concealed allocation and intention-to-treat analysis. This study was a clinic-based programme. Seventy-three patients with HAND were enrolled in the trial. The intervention comprised a moderate-intensity aerobic exercise, 20-60 min per session, three times per week, for twelve weeks. The control group received exercise education. Prevalence of HAND constituted the primary outcome. HAND was identified and classified following the Frascati criteria. We computed the odds ratio and number needed-to-treat to estimate the treatment effect. RESULTS: There were 73 patients (38 in exercise and 35 in control arm). Individuals in the exercise arm recorded a significantly higher reduction in working memory deficit (OR = 5.14; CI = 2.6-10.4; NNT = 6) but not in attention-deficit (OR = 0.31, CI = 0.2-0.5; NNT = -5) compared to the control group at twelve-week. Reductions in attention deficit (OR = 1.55, 95 CI = 1.0-2.4; NNT = 5) and HAND prevalence (OR = 1.8, 95 CI = 1.2-2.8); NNT = 8) were significantly higher in the exercise group compared the control group at three-month. No significant between-group difference in functional independence was observed immediately after exercise (p > 0.05). DISCUSSION: The neuroprotective effects of aerobic exercise appear selective and vary with cognitive abilities impaired and aerobic capacity, with a greater change occurring with improved aerobic capacity. CONCLUSION: Individuals with working memory and attention deficits may benefit more from moderate-intensity aerobic exercise.

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.

Normative scores for select neuropsychological battery tests for the detection of HIV-associated neurocognitive disorder amongst Nigerians.

Background: The study aimed to derive socio-demographic-corrected norms for selecting neuropsychological (NP) battery tests for people living with HIV (PLWHIV) in Nigeria. This cross-sectional study was conducted amongst patients who attended the general outpatient clinic and junior staff of the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla. Aims and Objectives: To determine the normative scores for select neuropsychological battery test for the detection of neurocognitive disorder amongst Nigerians PLWHIV. A sample of 92 individuals received voluntary HIV testing. Methods: Eligibility criteria were being HIV negative, aged 18-64 years and formal education. We undertook a brief neuromedical examination to identify putative exclusion criteria. We sampled four NP tests covering seven cognitive domains and the motor speed component of the International HIV Dementia Scale (IHDS-MS). We presented the normative scores using statistics of mean, median, standard deviation (SD), kurtosis and skewness. Results: All the participants were Nigerians aged 18-64 years. Most (74.1%) of the participants were females. The mean and median ages of the participants were 42.6 ± 11.42 years and 44 years, respectively. The effect of gender on NP performance was limited to the digit span test (DST)-forwards, while education affected all expect IHDS-MS and DST-backwards. The cut-off scores for defining mild and severe impairment varied (moving from 1SD to 2SD) for all cognitive domains except for IHDS-MS and DST. Conclusions: With these preliminary normative scores, it will be easier to identify and classify the severity of neurocognitive impairment amongst PLWHIV in Nigeria, thus facilitating the goal of keeping HIV-associated dementia to a minimum. The lack of variability in the IHDS-MS and DST is unfavourable.

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.

Nervous system disorders across the life course in resource-limited settings.

The resiliency of the adult nervous system is markedly affected by the environment and the circumstances during infant and child development. As such, adults in resource-limited settings who may have experienced early deprivation are particularly vulnerable to subsequent neurological disorders. Adult populations in countries with relatively recent advances in economic development may still have a higher susceptibility to neurological illness or injury that is reflective of the socioeconomic environment that was present during that population's infancy and childhood. Brain and peripheral nervous system research conducted over the past decade in resource-limited settings has led to an impressive and growing body of knowledge that informs our understanding of neurological function and dysfunction, independent of geography. Neurological conditions feature prominently in the burgeoning epidemic of non-communicable diseases facing low- and middle-income countries. Neurological research in these countries is needed to address this burden of disease. Although the burden of more prevalent and severe neurological disease poses public health and clinical challenges in settings with limited neurological expertise, the same factors, along with genetic heterogeneity and the relative absence of ingrained clinical care practices, offer circumstances well-suited for the conduct of crucial future research that is globally relevant.

Physical Activity Is Associated With Lower Odds of Cognitive Impairment in Women but Not Men Living With Human Immunodeficiency Virus Infection.

Background: Cardiovascular comorbidities are risk factors for human immunodeficiency virus (HIV)-associated cognitive impairment. Given differences in cardiometabolic risk profiles between women and men with HIV, we investigated whether associations between cardiometabolic risk factors and prevalent cognitive impairment differ by sex. Methods: Separate logistic regression models were constructed for women and men at entry into a prospective study of older persons with HIV (PWH) to assess the association of cardiometabolic and other risk factors with cognitive impairment. Results: Of 988 participants, 20% were women. Women had higher total cholesterol (194 vs 186 mg/dL; P = .027), hemoglobin A1c (5.9% vs 5.7%; P = .003), and body mass index (30.8 vs 27.4 kg/m2; P < .001) compared with men, and were less physically active (43% vs 55%; P = .005). In a multivariable model, physical activity was associated with lower odds of cognitive impairment in women (odds ratio, 0.35 [95% confidence interval, .15-.80]; P = .013) but not men. Conclusions: Physical activity may have a greater positive impact on cognitive health in women than in men with HIV. This finding should be confirmed in studies examining the longitudinal association between physical activity and incident cognitive impairment in PWH and the effect of interventions that increase physical activity on cognitive impairment in women with HIV.

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study.

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes. FUNDING: Chest, Heart and Stroke Scotland.

Prevalence and burden of epilepsy in Nigeria: A systematic review and meta-analysis of community-based door-to-door surveys.

BACKGROUND: Studies on prevalence of epilepsy in Nigeria yielded figures ranging between 3.1 and 37 per 1000, giving one of the widest variations in prevalence of epilepsy world over. In order to accurately estimate clinical and public health impacts of epilepsy in Nigeria, robust and reliable epidemiological data are required for an appropriate estimation of logistical, economical, and social impacts of epilepsy. OBJECTIVE: The objectives of the study were to determine, using meta-analysis, the prevalence of epilepsy by pooling data from community-based door-to-door surveys conducted in various parts of Nigeria, explore the existing variation in prevalence of epilepsy in Nigeria along geopolitical regions and settlement setting of the country, and then evaluate the burden of epilepsy in Nigeria. METHODS: Prevalence estimates were derived from a random effects meta-analysis of observational studies reporting the prevalence of epilepsy in Nigeria. The derived estimate for the prevalence of epilepsy was applied to the total populations in Nigeria to give an estimated burden of epilepsy in Nigeria. RESULT: Nine community-based door-to-door surveys, with quality data from different regions in Nigeria, were included. I-squared (I2) heterogeneity was 88.5%. Random effects model (REM) estimate of overall prevalence of epilepsy from the studies was 8 per 1000 (95% confidence interval (95% CI): 6-10). The prevalence was highest (11 per 1000) in the south western part of the country. It was also higher among the rural (15 per 1000 people) than the urban (6 per 1000) dwellers. The burden of epilepsy in Nigeria, based on the prevalence estimate was 1,280,000 persons (95% CI: 960,000-1,600,000 persons). CONCLUSION: In Nigeria, the estimated prevalence of epilepsy is 8 per 1000 people indicating a substantial burden of the disease in the country.

Predictors of mortality among older patients in the medical wards of a tertiary hospital in Nigeria.

BACKGROUND: Older people face the biggest challenges in the overburdened healthcare services in Nigeria especially when hospitalized. There is no reliable data on the predictors of mortality in this population. AIMS: To determine the predictors of mortality among older patients on admission in the medical wards of University College Hospital, Ibadan. METHODS: Using a prospective cohort design, we investigated 450 patients (> 60 years) from the day of admission to death or discharge. Variables assessed included sociodemographic, family dynamics, lifestyle habits, healthcare utilization, quality of life, frailty, anxiety, depression, cognition, functional disability and anthropometric parameters. Kaplan-Meier method and Log-rank test were used to estimate and compare survival functions, respectively. Cox proportional hazard regression analysis was used to determine the predictors of mortality. RESULTS: The mean age of the subjects was 71.5 ± 8.0 years and 234 (52.0%) were females. Overall, there were 99 (22.0%) in-hospital deaths. The median survival time (MST) was 36.0 ± 3.0 days [females = 40.0 ± 3.5 days vs males = 31.0 ± 4.5 days (p < 0.001)]. There was a significant negative correlation between MST and age (r = - 0.931). Predictors of mortality on Cox's proportional hazard regression analyses were male sex HR = 2.03 (95% CI 1.27-3.24), severe frailty HR = 2.07 (1.02-4.20), cognitive impairment HR = 1.90 (1.14-3.17) and having ≥ 5 morbidities HR = 1.94 (1.14-3.30). CONCLUSION: There was a high mortality among older patients particularly the frail, male or those with multiple morbidities. Prompt and holistic management of morbidities and targeted interventions for cognitive impairment and frailty are needed to improve survival during hospitalization.

Managing dementia in rural Nigeria: feasibility of cognitive stimulation therapy and exploration of clinical improvements.

Objectives: We investigated the feasibility and clinical impact of a psychosocial intervention, Cognitive Stimulation Therapy (CST), to help manage dementia in a rural setting in Nigeria. Method: People with dementia were identified from a prevalence study in Lalupon in the south-west of Nigeria. Prior to this feasibility study CST was adapted for the setting and pilot by our team. Fourteen sessions of CST were provided over a 7-week period by a trained nurse specialist and occupational therapist. Change in quality of life was the main outcome. Results: Nine people were enrolled in CST. Significant improvements in cognitive function, quality of life (physical, psychosocial and environmental domains), physical function, neuro-psychiatric symptoms and carer burden were seen. Conclusions: CST appears to be feasible in this setting, although adaptation for low literacy levels, uncorrected visual and hearing impairment and work and social practices is needed. The clinical improvements seen were encouraging.

Gender differential in inclination to donate brain for research among Nigerians: the IBADAN Brain Bank Project.

BACKGROUND: Laboratory-based studies of neurological disease patterns and mechanisms are sparse in sub-Saharan Africa. However, availability of human brain tissue resource depends on willingness towards brain donation. This study evaluated the level of willingness among outpatient clinic attendees in a Nigerian teaching hospital. METHODS: Under the auspices of the IBADAN Brain Bank Project, a 43-item semi-structured interviewer-administered questionnaire was designed to evaluate knowledge, attitude, and beliefs of individuals attending Neurology, Psychiatry and Geriatrics Outpatient clinics regarding willingness to donate brain for research. Association between participants characteristics and willingness towards brain donation was investigated using logistic regression models. Analysis was conducted using Stata SE version 12.0. RESULTS: A total of 412 participants were interviewed. Their mean age was 46.3 (16.1) years. 229 (55.6%) were females and 92.5% had at least 6 years of formal education. Overall, 109 (26.7%) were willing to donate brains for research. In analyses adjusting for educational status, religion, ethnicity, marital status and family setting, male sex showed independent association with willingness towards brain donation OR (95% CI) 1.7 (1.08-2.69), p = 0.023. Participants suggested public engagement and education through mass media (including social media) and involvement of religious and community leaders as important interventions to improve awareness and willingness towards brain donation. CONCLUSION: The survey revealed low willingness among outpatient clinic attendees to donate brain for research, although men were more inclined to donate. It is imperative to institute public engagement and educational interventions in order to improve consent for brain donation for research.

Sexual dysfunction among Nigerian women with epilepsy.

OBJECTIVES: Sexual dysfunction (SD) has been shown to be more prevalent among females with epilepsy (FWE) when compared with controls. Identified risk factors for SD among FWE include depression, antiepileptic drug (AED) type, epileptic lateralization, and temporal lobe involvement. Despite a huge population of FWE in sub-Saharan Africa and by extension Nigeria, there are limited studies on the effect of AEDs and epilepsy on sexual function among FWE in the region. We therefore studied predictors and patterns of SD among Nigerian FWE. METHOD: This was a descriptive study carried out at the University College Hospital, Oyo State - a tertiary hospital in South-Western Nigeria. The Zung Self-rating Depression Scale was used to assess mood. Sexual dysfunction was measured using the Arizona Sexual Experience Scale (ASEX) questionnaire. RESULTS: The frequency of clinically significant SD among FWE (35, 50.0%) was similar to that of controls (27, 38.6%; p = 0.173). However, the mean ASEX score was higher in FWE than in controls (p = 0.009). Using domains defined by the Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-V), we observed that FWE had higher scores in all domains. Sexual dysfunction was also more prevalent among FWE with lesional epilepsy when compared with those with nonlesional epilepsy. Standardized beta coefficients from multiple regressions conducted suggest that age of FWE, the presence of motor weakness, and systolic blood pressure contributed to SD. SIGNIFICANCE: Females with epilepsy had higher ASEX scores in all domains, with older FWE and those with lesional epilepsy more likely to have SD. Healthcare providers should pay attention to SD among FWE for improved quality of life.

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 stimulation therapy as a sustainable intervention for dementia in sub-Saharan Africa: feasibility and clinical efficacy using a stepped-wedge design.

BACKGROUND: Cognitive stimulation therapy (CST) is a psychosocial group-based intervention for dementia shown to improve cognition and quality of life with a similar efficacy to cholinesterase inhibitors. Since CST can be delivered by non-specialist healthcare workers, it has potential for use in low-resource environments, such as sub-Saharan Africa (SSA). We aimed to assess the feasibility and clinical effectiveness of CST in rural Tanzania using a stepped-wedge design. METHODS: Participants and their carers were recruited through a community dementia screening program. Inclusion criteria were DSM-IV diagnosis of dementia of mild/moderate severity following detailed assessment. No participant had a previous diagnosis of dementia and none were taking a cholinesterase inhibitor. Primary outcomes related to the feasibility of conducting CST in this setting. Key clinical outcomes were changes in quality of life and cognition. The assessing team was blind to treatment group membership. RESULTS: Thirty four participants with mild/moderate dementia were allocated to four CST groups. Attendance rates were high (85%) and we were able to complete all 14 sessions for each group within the seven week timeframe. Substantial improvements in cognition, anxiety, and behavioral symptoms were noted following CST, with smaller improvements in quality of life measures. The number needed to treat was two for a four-point cognitive (adapted Alzheimer's Disease Assessment Scale-Cognitive) improvement. CONCLUSIONS: This intervention has the potential to be low-cost, sustainable, and adaptable to other settings across SSA, particularly if it can be delivered by non-specialist health workers.