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, (β = -0.54,SE = 0.12,p-value = 7.50x10-6) in the discovery data set, and replicated this finding in Ibadan (β = -1.32,SE = 0.52,p-value = 1.15x10-2) and Puerto Rican (β = -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 (β = -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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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.
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.
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 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.
Abstract 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 ≥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 ≥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 ≥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.
To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort.
Two stage design with a screening interview followed ...by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels.
Indianapolis, Indiana.
From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included.
Incident dementia and incident AD.
After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD.
Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.
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.
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.
Prospective observation.
Nigeria.
Adult ischemic and hemorrhagic stroke survivors.
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).
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.
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.
Abstract 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 3 months. 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 3 months 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 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.
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