Alzheimer Disease: Ogunniyi A

Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, Luchsinger JA, Ogunniyi A, Perry EK, Potocnik F, Prince M, Stewart R, Wimo A, Zhang ZX, Antuono P, Anonymous00415. · Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK. · Lancet Neurol. · Pubmed #18667359 No free full text.

Abstract: Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.

Unverzagt FW, Sujuan Gao, Lane KA, Callahan C, Ogunniyi A, Baiyewu O, Gureje O, Hall KS, Hendrie HC. · Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · J Geriatr Psychiatry Neurol. · Pubmed #18004008 No free full text.

Abstract: This review begins with a historical accounting of the evolution of the concept of mild cognitive dysfunction, including nomenclature and criteria from Kral to Petersen. A critical analysis of the main elements relating to assessment and diagnosis of mild cognitive dysfunction is provided. Methodological limitations in design, measurement, and characterization, especially as they relate to older African Americans, are identified. Data from a 15-year longitudinal study of community-dwelling African Americans in Indianapolis, Indiana, indicate a 23% prevalence of all-cause mild cognitive dysfunction, with approximately 25% progressing to dementia in 2 years and another 25% reverting to normal cognition in the same interval. Factors contributing to this longitudinal variability in outcomes are reviewed, including the role of medical health factors. The review closes with suggestions for next steps in the epidemiological research of mild cognitive impairment.

Hendrie HC, Murrell J, Gao S, Unverzagt FW, Ogunniyi A, Hall KS. · Department of Psychiatry, and Center for Aging Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16917194 No free full text.

Abstract: Epidemiologic studies on dementia generally have 2 major interacting objectives: descriptive, where rates of dementia and Alzheimer Disease (AD) are calculated for communities and selected populations, and analytic, which attempt to explain the observed phenotypic variations in communities and populations by identifying disease risk factors. The public health benefits derived from descriptive studies are exemplified by the recent published review of the global prevalence of dementia under the auspices of Alzheimer Disease International. This review emphasized the enormous and growing burden associated with dementia particularly for countries in the developing world and outlined strategies to influence policy making, planning, and healthcare allocation. One interesting feature of descriptive studies on dementia is that although the few epidemiologic studies conducted in Africa suggest that rates of dementia and AD are relatively low, rates of AD and dementia have been reported to be relatively high for African Americans. The Indianapolis-Ibadan Dementia Project has reported that the incidence rates for AD and dementia in Yoruba are less than half the incidence rates for AD and dementia in African Americans. Analytic studies are now underway to identify risk factors that may account for these rate differences. The risk factor model being applied, attempts to identify not only putative genetic and environmental factors but also their interactions. So far the major findings have included: apolipoprotein E e4, a major risk factor for AD in most populations, is also a risk factor for AD in African Americans but not for Yoruba; African Americans are at higher risk not only for AD, but also for diseases associated with increased cardiovascular risk such as hypertension, diabetes, and metabolic syndrome; African Americans have higher rates of hypercholesterolemia than Yoruba: there is an interaction between apolipoprotein E e4, cholesterol, and AD risk in both Yoruba and African Americans. We eventually hope to create a risk factor model that will not only account for the dementia rate differences between Yoruba and African Americans, but also help explain dementia rates in other developing and developed countries.

Hall KS, Gao S, Baiyewu O, Lane KA, Gureje O, Shen J, Ogunniyi A, Murrell JR, Unverzagt FW, Dickens J, Smith-Gamble V, Hendrie HC. · Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. · Alzheimers Dement. · Pubmed #19426950 No free full text.

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 > 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.

Ogunniyi A, Hall KS, Gureje O, Baiyewu O, Gao S, Unverzagt FW, Smith-Gamble V, Evans RE, Dickens J, Musick BS, Hendrie HC. · Departments of Medicine and Psychiatry, University College Hospital, Ibadan, Nigeria. · Metab Brain Dis. · Pubmed #16850256 No free full text.

Abstract: INTRODUCTION: The incidence rate of Alzheimer's disease (AD) was found to be 2 times lower in Yoruba than in African Americans. This study was aimed at identifying the factors associated with increased risk of incident AD in the two communities. METHODOLOGY: A two-stage design with initial screening using the CSI'D followed by neuropsychological test battery, relations' interview and physician assessment in a sub-sample.NINCDS-ADRDA criteria were met for AD. The risk factor variables assessed included demographic, lifestyle, medical and family history items. RESULTS: In the Yoruba, AD was associated with age (OR = 1.07) and female gender (OR = 2.93). In African Americans, age (OR = 1.09) and rural living (OR = 2.08) were the significant risk factors, while alcohol was protective (OR = 0.49). DISCUSSION: Age was a significant risk factor for AD at both sites. The higher risk of incident AD in the Yoruba female, and in African Americans who resided in rural areas in childhood were similar with the prevalence cases. Alcohol emerged a protective factor in African Americans. More studies are required, including biological measurements, to adequately explain the differences in rates.

Hendrie HC, Lane KA, Ogunniyi A, Baiyewu O, Gureje O, Evans R, Smith-Gamble V, Pettaway M, Unverzagt FW, Gao S, Hall KS. · Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Int Psychogeriatr. · Pubmed #16640794 No free full text.

Abstract: BACKGROUND: Assessing function is a crucial element in the diagnosis of dementia. This information is usually obtained from key informants. However, reliable informants are not always available. METHODS: A 10-item semi-structured home interview (the CHIF, or Clinician Home-based Interview to assess Function) to assess function primarily by measuring instrumental activities of daily living directly was developed and tested for inter-rater reliability and validity as part of the Indianapolis-Ibadan dementia project. The primary validity measurements were correlations between scores on the CHIF and independently gathered scores on the Blessed Dementia Scale (from informants) and the Mini-mental State Examination (MMSE). Sensitivities and specificities of scores on the CHIF and receiver operator characteristic (ROC) curves were constructed with dementia as the dependent variable. RESULTS: Inter-rater reliability for the CHIF was high (Pearson's correlation coefficient 0.99 in Indianapolis and 0.87 in Ibadan). Internal consistency, in both samples, was good (Cronbach's alpha 0.95 in Indianapolis and 0.83 in Ibadan). Scores on the CHIF correlated well with the Blessed Dementia scores at both sites (-0.71, p < 0.0001 for Indianapolis and -0.56, p < 0.0001 for Ibadan) and with the MMSE (0.75, p < 0.0001 for Indianapolis and 0.44, p < 0.0001 for Ibadan). For all items at both sites, the subjects without dementia performed significantly better than those with dementia. The area under the ROC curve for dementia diagnosis was 0.965 for Indianapolis and 0.925 for Ibadan. CONCLUSION: The CHIF is a useful instrument to assess function directly in elderly participants in international studies, particularly in the absence of reliable informants.

Murrell JR, Price B, Lane KA, Baiyewu O, Gureje O, Ogunniyi A, Unverzagt FW, Smith-Gamble V, Gao S, Hendrie HC, Hall KS. · Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, USA. · Arch Neurol. · Pubmed #16533971 links to  free full text

Abstract: BACKGROUND: Alzheimer disease (AD) is the most frequent cause of dementia. Even though the incidence of AD in the African American population is similar to or higher than that in persons of European descent, AD in African Americans is understudied. Identification of genetic risk factors in African Americans is essential for understanding the etiology of AD. OBJECTIVE: To determine the effect of apolipoprotein E (APOE) genotype on the risk of AD in elderly African Americans. DESIGN: Population-based longitudinal study of AD. SETTING: Indianapolis, Ind. PARTICIPANTS: African Americans 65 years and older. MAIN OUTCOME MEASURES: APOE genotype and diagnosis of AD. RESULTS: The APOE genotype was determined in 1822 samples. Of these, 690 were clinically evaluated: 318 were normal, and 162 had a diagnosis of AD. The presence of APOE epsilon4 was significantly associated with increased risk of AD (epsilon3/epsilon4: OR, 2.32; 95% confidence interval [CI], 1.41-3.82; and epsilon4/epsilon4: OR, 7.19; 95% CI, 3.00-17.29, compared with the epsilon3/epsilon3 genotype). There was also a significant protective effect with APOE epsilon2 (epsilon2/epsilon2 and epsilon2/epsilon3: OR, 0.42; 95% CI, 0.20-0.89). CONCLUSIONS: These findings are in marked contrast to the lack of association between APOE and AD in the Ibadan, Nigeria, sample of this project. These results suggest that other genetic factors and different environmental influences may play a role in the risk for AD in individuals of African ancestry.

Hall K, Murrell J, Ogunniyi A, Deeg M, Baiyewu O, Gao S, Gureje O, Dickens J, Evans R, Smith-Gamble V, Unverzagt FW, Shen J, Hendrie H. · Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Neurology. · Pubmed #16434658 No free full text.

Abstract: OBJECTIVE: To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. METHODS: Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. RESULTS: Logistic regression models showed interaction after adjusting for age and gender between APOE-epsilon4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-epsilon4 allele, but not in those with APOE-epsilon4. There was no significant association between levels of triglycerides and AD risk in those without APOE-epsilon4. CONCLUSIONS: There was a significant interaction between cholesterol, APOE-epsilon4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.

Gureje O, Ogunniyi A, Baiyewu O, Price B, Unverzagt FW, Evans RM, Smith-Gamble V, Lane KA, Gao S, Hall KS, Hendrie HC, Murrell JR. · Department of Psychiatry, University of Ibadan, College of Medicine, Ibadan, Nigeria. · Ann Neurol. · Pubmed #16278853 No free full text.

Abstract: Since 1992, research teams from Indiana University and the University of Ibadan have been collecting and comparing data from two diverse, elderly populations to identify risk factors for dementia and Alzheimer's disease. Apolipoprotein E (APOE) was genotyped in 2,245 Nigerian samples. Of these, 830 had a diagnosis: 459 were normal, and 140 had dementia including 123 diagnosed with Alzheimer's disease. In contrast with other populations, the APOE epsilon4 allele was not significantly associated with Alzheimer's disease or dementia. This lack of association in the Yoruba might reflect genetic variation, environmental factors, as well as genetic/environmental interactions.

Ogunniyi A, Hall KS, Baiyewu O, Gureje O, Unverzagt FW, Gao S, Hendrie HC. · Department of Medicine, College of Medicine, University of Ibadan, Nigeria. · West Afr J Med. · Pubmed #16276708 No free full text.

Abstract: Recent epidemiological data, mainly from cross-cultural studies, have revealed that the burden of dementia and Alzheimer's disease (AD) the most common type, is significantly lower in developing than in the industrialized countries. Caring for individuals with dementia is a major consideration because most developing countries do not have the resources to provide comprehensive care in institutions. Home care that is practiced is ideal given the cultural scenario especially with the extended family support. Public policies on the care of the elderly however need to be well articulated and implemented. Hypertension was the most frequent medical co-morbidity of the demented subjects and about a third of subjects with AD were hypertensive, which may support vascular hypothesis in AD pathogenesis. The important behavioural disturbances experienced by caregivers and the associated stress levels were highlighted. The model used on the Indianapolis-Ibadan Dementia Study which involves periodic home visits, and empowerment of caregivers through regular meetings is envisaged to make caring for these individuals easier and adaptable in other African communities.

Hendrie HC, Hall KS, Ogunniyi A, Gao S. · Department of Psychiatry, Indiana University School of Medicine, Indiana University Center for Aging Research, Indianapolis 46202-2872, USA. · Can J Psychiatry. · Pubmed #15065742 No free full text.

Abstract: OBJECTIVE: To describe the construction of a disease model incorporating both genetic an environmental factors in the etiology of Alzheimer's disease (AD), using data generated from the Indianapolis-Ibadan dementia project (I-IDP). METHOD: The I-IDP is a longitudinal comparative study of the prevalence and incidence o dementia in 2 communities: elderly African Americans living in Indianapolis, Indiana, an Yoruba living in Ibadan, Nigeria. RESULTS: African Americans are more than twice as likely as Yoruba to develop AD. Possible explanations for this finding include genetic factors: the possession of the apolipoprotein E epsilon4 allele does not increase risk for AD among Yoruba but confers a sligh increase in AD risk for African Americans. As well, environmental factors may play a role: African Americans have a higher risk of vascular risk factors than do Yoruba. CONCLUSIONS: International comparative studies, particularly those involving population from developing and developed countries, offer a unique opportunity for applying new in formation regarding population genetics to traditional AD risk factor research.

Baiyewu O, Smith-Gamble V, Akinbiyi A, Lane KA, Hall KS, Ogunniyi A, Gureje O, Hendrie HC. · Department of Psychiatry, University of Ibadan, Ibadan, Nigeria. · Int Psychogeriatr. · Pubmed #15000419 No free full text.

Abstract: BACKGROUND: The Neuropsychiatric Inventory (NPI) has been used to assess behavioral symptoms of dementia in the United States, Taiwan, Japan, and Italy. METHOD: This report evaluates the use of the NPI to assess behavioral symptoms of dementia in a population of Yoruba, Nigerians aged 65 years and older who are subjects in the Indianapolis-Ibadan Dementia Project. In this study, the NPI, Blessed Dementia Scale, and Mini-Mental State Examination (MMSE) were used to assess Nigerian subjects with dementia. For this study the NPI was translated, back translated, and harmonized into Yoruba. RESULTS: The harmonized version of the NPI showed good interrater and test-retest reliability. The Cronbach alpha on 40 subjects was .80 for total severity score, .73 for frequency, and .73 for distress, indicating good internal consistency. The MMSE correlated with the NPI total score and severity scores of delusion, hallucination, and agitation, whereas the Blessed correlated with the NPI total score and severity scores of depression, anxiety, and nighttime behavior. CONCLUSIONS: The NPI was found to be a reliable tool to assess behavioral symptoms and caregiver distress of dementia in the Yoruba. Behavioral disturbances were as common in the Yoruba patients with dementia as in studies in other countries that have used the NPI, but the pattern of behavioral disturbances and caregiver response varied among the countries.

Smith-Gamble V, Baiyewu O, Perkins AJ, Gureje O, Hall KS, Ogunniyi A, Hui SL, Hendrie HC. · Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202, USA. · Am J Geriatr Psychiatry. · Pubmed #12427581 No free full text.

Abstract: OBJECTIVE: The authors conducted a longitudinal, population-based survey of African Americans in Indianapolis, Indiana, and Yoruba in Ibadan, Nigeria, using the Community Screening Interview for Dementia to assess the predictive value of informant reports of changes in personality on incident dementia and Alzheimer disease. METHODS: In all, 3,021 subjects had informants' reports of changes in personality and dementia status (2,084 subjects residing in Ibadan and 937 subjects residing in Indianapolis). RESULTS: After adjusting for demographic, cognitive, and functional characteristics in two markedly different populations, socioeconomically and culturally, subjects with changes in personality had approximately twice the odds of having dementia as subjects with no change in personality. CONCLUSION: The finding that in two markedly different populations, personality change is a significant predictor of future dementia, independent of cognition and functional status, should make clinicians particularly sensitive to these reports when they occur in their elderly patients.

Hendrie HC, Ogunniyi A, Hall KS, Baiyewu O, Unverzagt FW, Gureje O, Gao S, Evans RM, Ogunseyinde AO, Adeyinka AO, Musick B, Hui SL. · Department of Psychiatry, Indiana University School of Medicine, 541 Clinical Dr, Room 394A, Indianapolis, IN 46202, USA. · JAMA. · Pubmed #11176911 links to  free full text

Abstract: CONTEXT: Alzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced. OBJECTIVE: To compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations. DESIGN: The Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance. SETTING AND PARTICIPANTS: A total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively. MAIN OUTCOME MEASURES: Incident cases of dementia and AD in each of the 2 populations. RESULTS: The age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval [CI], 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]). CONCLUSION: This is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD.

Lahiri DK, Xu Y, Klaunig J, Baiyewu O, Ogunniyi A, Hall K, Hendrie H, Sahota A. · Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202, USA. · Ann N Y Acad Sci. · Pubmed #10672260 No free full text.

Abstract: The epsilon 4 allele of apolipoprotein E (APOE) is strongly associated with late-onset Alzheimer's disease (AD) in Caucasian populations, but our studies suggest that APOE epsilon 4 is not a risk factor for AD in Nigerian blacks and is a weak risk factor in African-Americans. The prevalence of AD is lower in Nigerians than in African-Americans. Increased oxidative damage to macromolecules in brain tissue by reactive oxygen species (ROS) has been reported in AD. Here we examined the effects of endogenous and induced oxidative stress on total (nuclear and mitochondrial) DNA damage in lymphoblastoid cell lines (5 probable AD and 3 controls) from Ibadan, Nigeria. Cells were exposed to 200 microM t-butyl peroxide (a generator of ROS) for 4 hours. Total DNA was isolated and digested with nuclease P1 and alkaline phosphatase. DNA fragments were separated by HPLC and the levels of 8-hydroxy-2'-deoxyguanosine (OH8dG, an indicator of DNA damage) and deoxyguanosine (dG) determined. We did not detect a significant difference in the OH8dG/dG ratio in untreated or treated cell lines in the two groups, and this was independent of APOE genotype. We also examined, by Western blotting, the level of beta-amyloid precursor protein (APP) which is involved in AD. The level of the heat shock protein (HSP-70) was examined as a control. There was a slight decrease in levels of APP and HSP-70 following treatment. Studies in cell lines from Caucasian subjects have shown an increase in mitochondrial DNA damage following oxidative challenge. Our preliminary results suggest that African populations are less vulnerable to chemical-induced oxidative DNA damage.