Epidemiology of dementia in Nigeria: results from the Indianapolis]Ibadan study

European Journal of Neurology 2000,7: 485]490 Epidemiology of dementia in Nigeria: results from the Indianapolis]Ibadan study A. Ogunniyi a, O. Baiyewu b, O. Gureje b, K. S. Hall c, F. Unverzagt c,s.h.siu c, S. Gao c, M. Farlow d, O. S. A. Oluwole a, O. Komolafe a, H. C. Hendrie c Departmentsof a Medicineand b Psychiatry, Collegeof Medicine, Universityof Ibadan, Nigeria and Indianapolis Studyof Health and Ageing, Indiana; and Departments of c Psychiatry and d Neurology, Indiana University School of Medicine, Indiana, USA Keywords: Alzheimer's disease, cross-cultural study, dementia, epidemiology, prevalence, risk factors Received 7 January 2000 Accepted 9 May 2000 We determined the prevalence of dementia in a cohort of 2494 elderly Nigerians residents in Idikan Community, Ibadan, Nigeria. We utilized the Community Screening Instrument for Dementia to select subjects for clinical assessment in the second stage. The findings were compared with those of 2212 African Americans living in Indianapolis, studied simultaneously using similar methodology. The overall age-adjusted prevalence rates of dementia and Alzheimer's disease in Ibadan were 2.29% and 1.41%, respectively. These rates were much lower than the respective values of 8.24% and 6.24% obtained for African Americans. In Ibadan, Alzheimer's disease accounted for 64.3% of the cases, with old age and female gender being the significant risk factors, whilst `living with others' appeared to be protective (P, 0.05). Amongst African Americans, on the other hand, old age, rural living below the age of 19 years, low educational attainment and family history of dementia were the risk factors. There was a lack of association between Alzheimer's disease and possession of the apolipoprotein E e4 allele in the Nigerian sample, unlike the finding in African Americans, where significant association was shown. In addition, the frequencies of the vascular risk factors investigated were lower in Nigerians. Our results showed lower prevalence of dementia and Alzheimer's disease in Nigerians, compared with African Americans. There was no association between Alzheimer's disease and apolipoprotein E (e4 allele) in the former. The differences in the frequencies of vascular risk factors between Nigerian subjects and African Americans would suggest involvement of environmental factors in disease process. Background Dementia research is still in its infancy in Africa because of the relatively younger population. According to the World Health Organization, only about 3% of the population is older than 65 years of age in Africa. This proportion is small when compared with the ratio in other regions of the world (WHO, 1996). The average life expectancy is below 60 years in many African countries. The major problems facing these countries are: malnutrition, poverty, high infant mortality, famine, wars and political instability. Infectious diseases therefore constitute a more Correspondence: A. Ogunniyi, Department of Medicine, University College Hospital, PMB 5116, Ibadan, Nigeria (fax: +234 22410489; e-mail: dementia.uch@skannet.com.ng). Paper delivered in part at the15th International Conference, Alzheimer's Disease International, Johannesburg, South Africa, 15]18 September 1999. daunting problem, and problems of the elderly are relegated to the background. There is also the impression that dementia, and in particular, Alzheimer's disease is more of a western disease, which was rarely diagnosed in developing countries (Henderson, 1986). Our preliminary studies suggested that dementia was relatively uncommon (Ogunniyi et al., 1992). However, Schoenberg et al. (1985) have shown in studies in biracial communities in the United States that dementia occurs in people of African descent as often as in Caucasians. Studying migrant populations such as Africans in Diaspora and comparing them with those living in places of their ancestral origin could provide clues on possible risk factors which may be environmentally determined and could provide grounds for rational institution of preventive measures (Osuntokun et al., 1992). This consideration led to the Indianapolis]Ibadan dementia research studies which began in 1991 with longitudinal follow up of the subjects to provide information on prevalence, incidence, ß 2000 EFNS 485

486 A. Ogunniyi et al. mortality and risk factors. Our findings to date are highlighted in this communication and compared with the results of other studies. Descriptive studies The prevalence study took place between1992 and1994 in Idikan Ward of Ibadan city. The people belong to the Yoruba ethnic group who inhabit south-western Nigeria and extend to neighbouring Benin Republic to the west. They are predominantly petty traders, farmers and artisans with stable population. There is minimal technological development in the ward.the subjects were studied simultaneously with African Americans in Indianapolis using similar methodology, which essentially involved in two stages. In Ibadan, a total of 2494 out of 2535 eligible individuals, aged 65 years and over, entered the study. Fortyone subjects (1.6%) either refused or were too sick to participate. Sixty-five percent of those studied were females, their mean age was 72.3 years (SD 67.5) and only 15.2 % of them were educated.the mean number ofyears of education was 0.8 years. In Indianapolis, out of the 2582 eligible persons, a total of 2212 subjects entered the study; 249 (9.6%) refused, and 121 (4.7%) were too sick to participate.the 2212 subjects studied again comprised 65% females, who were slightly older (mean age = 74 years; SD 67.0) and had a higher literacy rate (97.9%) than the Nigerian sample. All the subjects gave informed consent to participate. In the first stage, trained interviewers administered the pilot-tested and validated Community Screening Instrument for Dementia to all the subjects. This comprised a cognitive testing section and a relative's interview. From the performance of each subject, a discriminant function score was derived which was used to select subjects for clinical assessment in the second stage (Hall et al., 1996). The mean cognitive scores in Ibadan and Indianapolis were 28.0 and 30.4 (perfect score = 33).The subjects were divided into three performance groups on the basis of their discriminant function score, namely good, intermediate and poor performance categories. Five percent of the good performers (75% of them older than 75 years of age), along with 50% of the intermediate and all the poor performers were selected for assessment during the second stage. The performance of the subjects on the Community Screening Instrument for Dementia was similar in both sites, with 80.9, 7.8 and 11.2% of the subjects in the good, intermediate and poor categories, respectively, in Ibadan, compared with 80.6%, 7.6% and 11.8% in Indianapolis (Hendrie et al.,1995; Hall et al., 1996). Second stage assessment included a structured interview with an informant of the subject, preferably the spouse, focusing on cognitive functions, activities of daily living, social habits and past/current medical history. Each subject had detailed neuro-psychological testing, followed by clinical examination. Relevant laboratory tests were carried out at this stage, including brain computed tomography scan. Details of the procedure were described by Hendrie et al.(1995)andhallet al. (1996). All the data obtained were then collated and used in making consensus diagnosis first within each site and later blindly, intersite.the diagnoses were made along the lines of CERAD (Consortium to Establish a Registry for Alzheimer's Disease; Morris et al., 1989) and were categorized as: normal, cognitively impaired and demented. The diagnosis of dementia subtypes was based on clinical findings and not on neuropathology. For this, we conformed with the Diagnostic and Statistical Manual ] 3rd edn revised (DSM-IIIR) of the American Psychiatric Association (1987), International Classification of Diseases (ICD)-10 (WHO, 1988) and NINCDS- ADRDA (National Institute of Neurological and Communicative Disorders and Stroke, and Alzheimer's Disease and Related Disorders) criteria (McKhan et al., 1984). The independent diagnoses of investigators at the two sites had to agree, and discrepancies whenever they occurred were resolved during joint investigators' meeting. Statistical methods For the community samples from Indianapolis and all subjects in Ibadan, we modelled, for all of the clinically assessed subjects, the probability of dementia as a func- Indianapolis a Age group (years) Ibadan a Community Nursing home Combined Table 1 Prevalence of dementia (in percentages) by site 65]74 0.86 (0.52) 1.83 (1.58) 45.83 2.62 (1.58) 75]84 2.72 (1.69) 6.73 (4.99) 72.22 11.43 (8.02) 85 þ 9.59 (5.91) 17.07 (14.99) 76.32 32.44 (28.85) Overall (age-adjusted) 2.29 (1.41) 4.82 (3.69) ] 8.24 (6.24) a Prevalence of Alzheimer's disease in parentheses. Hendrie et al. (1995).

Epidemiology of dementia in Nigeria 487 Factors Ibadan Indianapolis Age 1.15 (1.12]1.18) 1.16 (1.11]1.21) Female sex 13.9 (3.85]50.28) 0.72 (0.30]1.76) Living condition: Rural residence to age19 1.57 (0.35]7.08) 2.49 (1.05]5.88) versus urban Living with spouse 1.00 (reference group) 1.00 (reference group) Living with others 0.06 (0.01]0.49) 0.87 (0.30]2.52) Living alone 0.48 (0.06]9.73) 0.53 (0.23]1.20) Family history of dementia b 5.40 (1.99]14.62) Education < 7 years of schooling ] 3.49 (1.06]11.48) 7]9 years of schooling ] 1.32 (0.46]3.78) 10 + years of schooling ] 1.00 (reference group) No education vs. any 2.15 (0.37]12.36) ] Table 2 Odds ratio estimates of the risk factors for Alzheimer's disease by site a a Ninety-five per cent confidence intervals are included in parentheses. Significant factors in bold print. b Unable to calculate odds ratio because of the small number of Alzheimer's disease subjects with family history of dementia. Hall et al. (1996). tion of the subject's age, sex and performance group on the screening test, using weighted logistic regression models (accounting for the sampling selection for clinical assessment). The mean predicted probability of dementia was used to estimate age-specific prevalence rates of dementia and Alzheimer's disease. This method gives more reliable and stable estimates than the direct standardization method according to Becket et al. (1992).The nursing home subjects were not included in the modelling procedure. Instead, direct rates of dementia were calculated for each age group.the overall age-specific rates for Indianapolis were derived as a weighted mean of the community prevalence rate and the nursing home prevalence rate. The weights were based on the proportion of individuals in the age group, who were living in nursing homes, as reported in the 1990 census for the state of Indiana. Findings A total of 28 subjects were diagnosed as demented in Ibadan. They included 20 females and eight males, with a mean age of 81 years (SD 69.9), which was higher than that of the total sample. The commonest type of dementia was Alzheimer's disease, diagnosed in 18 cases (64.3%). Eight (28.6%) had vascular dementia, and there was one case each of dementia with parkinsonism and depression (Hendrie et al., 1995; Ogunniyi et al., 1997). In the Indianapolis community, 65 subjects were diagnosed as demented and they comprised 49 Alzheimer's disease cases (75.4%), 10 vascular dementia (15.4%) and six cases with other dementia subtypes (Hendrie et al., 1995). The prevalence rates of dementia and Alzheimer's disease were significantly lower in Ibadan than in Indianapolis for each age-group, and overall, as shown in Table 1. The possible explanations for the rate differences between sites included higher mortality rates in Ibadan, with consequent shorter disease duration, lower disease incidence, or the presence of protective factors which were likely to be environmentally determined. Analytical studies The identification of populations with significantly different rates of dementia and living in different environments, such as our cohorts, facilitated the search for possible environmental risk factors, since the subjects are presumed to be from the same genetic stock. Cooper et al. (1999) have reported that about 75% of genetic heritage may be shared by African Americans and Nigerians. The screening questionnaire included information on socio-demographic variables (gender, age, marital status, education, living conditions including household composition), social habits, antecedent medical illness(es) as well as family history of dementia. Responses obtained from each subject were verified with a key informant. The frequencies of the putative risk factor variables were compared according to the diagnostic status of the subjects, and for Table 3 Comparison of vascular risk factors by site Vascular risk factor a Ibadan Indianapolis History of hypertension 19% 61% History of diabetes 2.5% 24% History of stroke 1.3% 11% Ever smoked 24% 63% Mean body mass index 21.4 28.9 Mean systolic BP (mmhg) 135 146 Mean diastolic BP (mmhg) 81 81 Mean cholesterol (mg/ml) 166 221 a All statistically significant at 0.05 level except mean diastolic BP.

488 A. Ogunniyi et al. Table 4 Apolipoprotein E genotypes in African Americans and Nigerians Indianapolis Ibadan Total number 276 156 Number with Alzheimer's disease a 60 21 E4 allele in Alzheimer's disease a cases 34.2% 19.1% E4 allele in normal subjects 21.8% 19.8% P-value 0.005 > 0.5 a AD, Alzheimer's disease. each site, to determine the factors significantly associated with the diagnosis of dementia, and in particular Alzheimer's disease. The height and weight measurements of each subject were used to calculate the body mass index. Blood pressure measurements (available for all subjects) and cholesterol results (obtained in 228 and 117 subjects in Ibadan and Indianapolis, respectively) were compared in a similar fashion. Weighted logistic regression models were used to derive odds ratios of risk factors for Alzheimer's disease, adjusting for age and gender. Due to the difference in education levels between the two populations, subjects in Indianapolis were categorized into three groups (0]6, 7]9 and 10 + years of schooling), whilst the subjects were categorized into `no schooling' vs. `any schooling' in Ibadan. Comparisons of vascular risk factors between Indianapolis and Ibadan were conducted using t-test for continuous variables (body mass index, systolic and diastolic blood pressure measurements and cholesterol) and x 2 -test for categorical variables. Comparisons of the apolipoprotein E allele frequencies in Alzheimer's disease subjects and normal subjects were conducted using x 2 -test for both sites. In Ibadan, the significant risk factors were old age and female gender as shown intable 2. Living with others appeared to be protective, although the strength of association was very weak.we found that13.2% ofelderly subjects in the Idikan community lived alone, compared with 46% of African Americans. In Indianapolis, old age, rural living before19 years of age, family history of dementia, and low educational attainment were the significant risk factors, as reported by Hall et al. (1998), and were similar to the findings in other studies reviewed by van Duijn (1996). A comparison of the frequencies of vascular risk factors between sites revealed significantly higher values in African Americans for virtually all the factors investigated, apart from the mean diastolic blood pressure values, as shown in Table 3. However, more African American subjects were already on anti-hypertensive therapy and this could have influenced the blood pressure recordings. The frequency of apolipoprotein E e4 allele in non-demented African Americans was 21.8%, against 34.2% in Alzheimer's disease subjects.the difference was statistically significant and the odds ratio for two copies of the e4 allele was 3.99 (95% confidence interval = 1.19]13.35), as reported by Sahota et al. (1997, 1998). On the other hand, the e4 allele frequencies in Nigerian controls and Alzheimer's disease subjects were 19.8 and 19.1%, respectively, which lacked any association (Osuntokun et al., 1995) as shown intable 4. Comments Our results showed consistent performance of the two study groups on items of the Community Screening Instrument for Dementia despite their educational and cultural differences. This implies that the screening questionnaire is suitable for studying disparate populations. The Community Screening Instrument for Dementia has subsequently been used in studies in China and Jamaica, after it was first used in a comparative study of Canadians and Cree Indians inwinnipeg (Hendrie et al., 1993). The prevalence rates of both dementia and Alzheimer's disease were significantly lower in the Nigerian community. In both study populations however, there was a progressive rise in the age-specific prevalence rates with increasing age, in agreement with findings in other studies (Schoenberg et al., 1985; Henderson, 1986; Rocca et al., 1986; van Duijn, 1996). The overall age-adjusted prevalence rate obtained for the African Americans was within the range of 5]11% reported in most studies in western countries (Rocca et al., 1986; van Duijn, 1996). The lower prevalence rate in Ibadan, similar to the findings in other studies in developing countries as compiled by the 10/66 Dementia Research Group (1999), would suggest that western life style and/or other environmental factors have a role to play in the disease process. Other possible explanations include lower incidence and/or higher mortality of the cases. Our study showed that Alzheimer's disease was the most common type of dementia, with vascular dementia as the second, in agreement with studies in western countries (Henderson, 1986; Rocca et al., 1986; van Duijn, 1996). We found a consistent effect of age as a risk factor for Alzheimer's disease in both sites, despite the differences in prevalence rates. This similarity in the odds ratio values, with respect to age between sites, would suggest that biological processes associated with ageing are essential elements in the development of Alzheimer's disease, but that genetic and environmental risk factors may affect age-specific rates. Old age is a consistent risk factor for dementia in virtually all studies, including ours (Schoenberg et al., 1985; Henderson, 1986; Rocca et al., 1986; Hendrie et al., 1995; van Duijn, 1996; Hall et al., 1998). Association of Alzheimer's disease with female gender has been reported inconsistently in studies (Rocca et al.,

Epidemiology of dementia in Nigeria 489 1986; van Duijn, 1996). In the Nigerian cohort, females appeared to have a higher chance of developing Alzheimer's disease, unlike the case with African Americans. Out of the 18 cases of Alzheimer's disease in Ibadan, 16 were females (88.9%). The females studied were older, with less education and hence were likely to have performed poorly during screening. However, since the total number of Alzheimer's disease cases overall was small, this association needs to be explored further in subsequent studies. Communal living, which is the traditional African style, appears to be protective against the development of Alzheimer's disease, although the strength of the association is very weak. Such a living arrangement could enable the older persons to derive more psycho-social stimulation which may possibly enhance cognitive functions. In supportofthis is the finding in a recent study in America by Bassuk et al. (1999), which reported that social engagement enhanced cognitive functions in the elderly. Unfortunately, with modernization in Africa, erosion and dismantling of the extended family system which served as a buffer is likely to occur (Osuntokun et al., 1992). The changing trend may portend a grave situation as regards predisposition to dementia. One however, must be careful in the interpretation of this result because association is not synonymous with causation. The living conditions of the two communities are different. African Americans enjoy considerably better living standards and they also live longer. They have access to good health care facilities and better nutrition. According to WHO latest demographic data (WHO, 1999), in America the average life expectancy for males is 73 years, and for females is 80 years, whereas in Nigeria, the respective values are 49 and 52 years. It was therefore worthwhile investigating the possible contribution of environmental factors in explaining differences in disease rates. Hence the need to compare vascular risk factors between sites. Apolipoprotein E (e4 allele) is an established susceptibility factor for Alzheimer's disease in Caucasians and was found to be significantly associated with Alzheimer's disease in African Americans (Sahota et al., 1997; Sahota et al., 1998), in keeping with other results in western countries. However, we found no association of the e4 allele with Alzheimer's disease in Nigerians (Osuntokun et al.,1995), which could be interpreted to mean that there may be environmental and/or genetic factors mitigating against its effect.the possible reasons for this lackof association include reduced b amyloid turnover, reduced environmental exposure, reduced oxidative DNA damage, or presence of as yet unidentified protective factors, which may be dietary. Sayi et al.(1997) found e4 allele frequency of 25% in both demented and age-matched, non-demented elderly Kikuyus in East Africa, which agreed with our finding of no association between APOE e4 allele and Alzheimer's disease in the Nigerian cases. It will be worthwhile to investigate this lack of association in other African populations and then proceed to determining the relevance of this finding in disease prevention. The Nigerian subjects had much lower cholesterol levels and lower frequencies of vascular risk factors in general, which have been shown in recent studies to be associated with cerebral atherosclerosis and Alzheimer's disease (Skoog, 1999).The role of vascular factors needs further investigation in other African countries as well. In conclusion, our study showed that dementia, and in particular Alzheimer's disease, is not rare in Nigerians, although the prevalence is at the present time lower than in western countries, and that Alzheimer's disease is the most common type in the community studied. The differences in the frequencies of the risk factors for Alzheimer's disease between sites suggest environmental differences which we opine have some role to play in the disease process. The search for other risk factors would entail longitudinal studies. Replication of these results in other communities in Nigeria and other African countries is necessary before widespread generalizations about the epidemiology of dementia in the African continent can be made. Our results have shown that cross-cultural studies of migrant populations are very useful when investigating the possible interaction of nature and nurture in dementia research. Such carefully planned and executed studies can make substantial contributions to preventive strategies. Acknowledgements The Indianapolis]Ibadan Study was supported by the National Institutes of Ageing grants PHS RO1 AGO9956]06 and P30 AG10133]06, and Alzheimer's Association/F.M. Kirby Foundation (1995]98) Pilot Research Grant IIRG-95]084. References 10/66 Dementia Research Group (1999). Methodological issues for population-based research into dementia in developing countries: a position paper. Int J Geriatric Psychiatry 15:21]30. American Psychiatric Association. (1987). Diagnostic and Statistical Manual for Mental Disorders. 3rd edn.washington. Bassuk SS, GlassTA, Berkman LF (1999). Social disengagement and incident cognitive decline in community-dwelling elderly persons. Ann Int Med 131:165]173. Beckett L, Scherr P, Evans D (1992). Population prevalence estimates from complex samples. JClin Epidemiol 45:393]402. Cooper RS, Rotimi CN,Ward R (1999). 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