Studies on Dementia. Dementia and Ethnicity CANDIDA GRAHAM, ROBERT HOWARD, AND YVONNE HA DEMENTIAS WITH A KNOWN ETHNIC AND GEOGRAPHIC BIAS

Transcription

1 International Psychogeriatrics, Vol. 10, No. 2, 1998, pp international Psychogeriatric Association Studies on Dementia Dementia and Ethnicity CANDIDA GRAHAM, ROBERT HOWARD, AND YVONNE HA ABSTRACT. Ethnic differences in rates of dementia nationally, within multiethnic communities, and internationally have important repercussions. The question Do ethnic differences exist in rates of dementia? is a crucial one that has implications for service delivery and also offers opportunities for future research on possible etiological factors. Epidemiological surveys suggest that ethnic and geographical differences do occur in rates of dementia, but cross-cultural surveys are fraught with problems. The need for further methodologically sound, cross-cultural comparative studies is paramount to confirm or disclaim the ethnic differences observed to date. The subject of dementia and ethnicity has gained recent interest within the field of geriatric psychiatry. The question whether ethnicity has a bearing on rates of distribution of dementia is a crucial consideration when planning service delivery and allocation of resources within the multiethnic communities of Western countries and also when creating appropriate elderly services within developing countries. If ethnic differences do exist, these differences may be due to racial genetic factors, shared cultural practices, or common environmental factors. Therefore, the subject area offers the opportunity for comparative studies From the Behavioural Psychotherapy Unit, The Bethlem Royal Hospital, Beckenham, Kent, UK (C. Graham, MMedSci, MRCPsych), and Section of Old Age Psychiatry, The Maudsley Hospital, London, UK (R. Howard, MD, MRCPsych; and Y. Ha, MB BS). Offprints. Requests for offprints should be directed to Candida Graham, MMedSci, Behavioural Psychotherapy Unit, The Bethlem Royal Hospital, Monks Orchard Road, Beckenham, Kent BR3 3BX, UK. crg09@aol.com Received January 22, 1998 Accepted April 20, 1998 to search for such etiological factors and possible protective factors. Dementia can result from either direct pathological changes to the cerebral cortex (e.g., the plaques and tangles of Alzheimer s disease) or neurological and multisystem disorders that produce a dementing process as a part of a larger disorder. These multisystem disorders produce cortical changes and distal systemic pathology, e.g., Huntington s disease, syphilis, AIDS. DEMENTIAS WITH A KNOWN ETHNIC AND GEOGRAPHIC BIAS Many causes of dementia are known to display ethnic and geographical clustering. Huntington s disease is a genetically inherited disorder that produces peripheral neurological symptoms and a dementia that is insidious in onset and has associated subcortical features. It is produced by a single autosomal dominant 183

2 184 gene mutation located on chromosome 4 and has a virtually 100% rate of penetrance. Specific populations have been shown to have particularly high rates of occurrence due to family genetic clustering: Tasmania (Myrianthopoulos, 1966) and the Moray Firth area of Scotland (Lyon, 1962). Conversely, because of ethnic genetic factors, very low rates have been reported in Japan (Myrianthopoulos, 1966). Prion dementias, the human spongiform encephalopathies, are represented by Creutzfeldt- Jakob disease, Gerstmann-Straussler syndrome, and kuru. All three disorders are characterized by the diagnostic neuropathological changes of spongy degeneration affecting the cerebral grey matter, neuronal loss, proliferation of astrocytes, and the presence of an abnormal protease-resistant protein-prion protein-within the brain. The pathology produces the clinical picture of a rapidly deteriorating dementia with myoclonus, varying degrees of ataxia, and lower motor neuron signs. Prion disease can be horizontally transmitted, but a significant proportion of cases is familial with an autosomal dominant pattern of inheritance. Geographical clusters of cases have been reported in Libyan Jews in Israel (Kahana et al., 1974), as a result of familial clustering, and in the Fore tribe in the eastern highlands of New Guinea (Beck et al., 1966) as a result of ethnic cultural practices placing them at increased risk of horizontal transmission, e.g., cannibalism of dead relatives. Parkinson dementia complex of Guam is a dementing process with associated features of Parkinson s disease found with extraordinary frequency among the indigenous population of the Island of Guam in the Western Pacific (Kurland& Mulder, 1954). Here the incidence is 100 C. Graham et al. times greater than in the USA (Lessell et al., 1962). Cases tend to occur in a familial manner, but no clear pattern of inheritance has emerged. This ethnic difference is surmised to be due to a shared environmental factor in addition to genetic factors. Ethnic differences clearly do occur in these more uncommon forms of dementia. The differences are due to genetic factors (low rates of Huntington s disease in the Japanese), shared cultural practices (kuru in the Fore tribe), or a combination of genetic predisposition and deleterious environmental factors (Parkinson dementia complex of Guam). What of those dementias most prevalent in Western society-senile dementia of the Alzheimer type (SDAT) and vascular dementia (VaD)? Do ethnic differences occur in the prevalence and incidence of these conditions? DIFFICULTIES IN COMPARISON OF CROSS-CULTURAL DEMENTIA RATES Cross-cultural surveys of dementia rates are fraught with problems for researchers. Numerous factors can act as confounding variables producing artifactual differences in incidence and prevalence rates. Some of these factors are as follows: Diagnostic criteria and methods of identifying cases differ frequently among epidemiological surveys, making meaningful comparison difficult. Formal tests of cognitive ability are culture-dependent. English-speaking participants and those with higher levels of education score more highly on neuropsychological testing (Bohnstedt et al., 1994; Loewenstein et al., 1992, 1993; Teresi et al., 1995) International Psychogeriatrics, 10(2), June 1998

3 Dementia and Ethnicity There may be underreporting of dementia in developing countries because of the following reasons: A stigma is often attached to having a relative with dementia; relatives and caregivers may see a person s declining cognitive function as a normal part of aging; or the cognitive decline may not be noticed because elders in developing countries are frequently freed from household responsibilities that would identify the decline. High rates of coexisting physical morbidity in the elderly occur in some developing countries; this produces functional disability that may mask cognitive decline in the elderly. Selective high mortality rates in patients with dementia may occur in developing countries and produce artificially low prevalence rates. This point was highlighted by Henderson (1994), who observed that prevalence rates are of limited value when etiology is considered, because variations in rates may be a consequence of different survival times after dementia has developed. Sample populations will differ in factors that have an impact on dementia rates, e.g., age, level of education. With these difficulties in mind, we review below a number of surveys that have been undertaken to determine whether cross-cultural differences in rates of dementia exist. DEMENTIA RATES IN EUROPE AND NORTH AMERICA Prevalence rates of dementia in Europe and the US ranged between 3.1% and 6.1% (Bachman et al., 1992; Copeland et al., 1987; Essen-Moller, 1956; Folstein et al., 1985; Weissman et al., 1985), with SDAT accounting for approximately 50% 185 and VaD for approximately 25%. Incidence rates from the 3-year follow-up study of a Liverpool community sample (Copeland et al., 1992) using a semistructured interview and computerassisted diagnosis (GMS-AGECAT) gave an overall incidence of dementia of 9.2/ 1,000/ year, with SDAT at 6.3/ 1,000/ year and VaD at 1.9/1,000/year. By metaanalysis of studies between 1945 and 1985, Jorm and colleagues (1987) reported a trend for higher rates of SDAT in rural versus urban areas, and for the prevalence of SDAT to be higher than that of VaD in Europe and North America, whereas the reverse was found in Japan and Russia. The studies reviewed by Jorm and colleagues (1987) gave prevalence rates ranging from 0.5% for those aged 61 and over in Taiwan (Lin et al., 1969) to 18.5% for those aged 65 and over in Denmark (Nielsen, 1962). The authors concluded, however, that any possible regional variations could not be interpreted because of the vastly differing methodologies of the studies reviewed. Although national rates of dementia are well reported within the US and Europe, only a few studies have sought to refine these rates by assessing the relative contributions made by the different ethnic groups within a country. Some national cross-cultural studies in the USA have identified ethnic differences in rates of dementia. African Americans appear to be at higher risk of dementia than White Americans. Schoenberg and colleagues (1985) reported an age-adjusted prevalence rate of dementia, in a community sample of 8,925, of 817 per 100,000 for Whites and per 100,000 for African Americans. Heyman and colleagues (1991) used a stratified random community sample of African Americans (N = 83) and White Americans

4 186 (N = 81) aged over 65 years. They found prevalence rates of dementia of 16% for African Americans and 3.05% for Whites. Both studies appeared to have observed true rates of difference in the rates of dementia, because of the consistency of methodology within each study; unfortunately the authors did not control for rates of survival, so the observed differences in prevalence rates may be artifactual. Silverman and colleagues (1992) undertook a family history survey using 924 elderly nondemented index subjects of different ethnic statuses. All participants lived in New York and were attending a senior citizen center sponsored by the New York City Council. A total of 305 participants were Chinese, 212 Jewish, 215 Italian, and 192 Puerto Rican. Ninety-five cases of dementia were identified among 6,866 first-degree relatives: 79% of cases were identified as SDAT and 9% as VaD. The proportion of VaD was significantly higher among Chinese cases (25%) than among the Jewish cases (6%), Italian cases (9%), and Puerto Rican (0%) cases. The Jewish and Italian groups had a significantly increased cumulative risk for SDAT (relative risk comparison to Chinese cases: Italian2.98, Jewish 2.86, Puerto Rican 1.01). Although these ethnic differences in the rates of dementia appear impressive, the authors acknowledge the limitations of their results. Biased sampling would have occurred by accessing volunteers attending a senior citizen center, and the family-history method is an inherently less accurate method than the direct investigation of subjects. The findings may also be a result of reporting biases due to differences in participants knowledge of family members, their education levels and cultural taboos in identifying relatives with mental health problems. C. Graham et al. In contradiction to the three former studies, no ethnic differences were found by Pittman and colleagues (1992). These authors undertook a community-based study to evaluate dementia using neuropsychological test batteries and physician diagnoses. The survey of 430 subjects included 29.1% Black and 33.4% Hispanic. A total of 9.8% of the sample population had dementia. Once the authors had controlled for the effect of education, no ethnic differences in rates of dementia were noted. Unfortunately, as with the study of Silverman and colleagues (1992), sample biasing occurred because the authors used volunteers participating in an aging project; and although the authors were able to control for educational level by using clinical judgment during interviewing, this inherently brings into play the possibility of subjective bias of the interviewer. DEMENTIA RATES IN ASIA Several studies have reported low prevalence rates of dementia in China (review by Zhang et al., 1990). Li and colleagues (1989, 1991) undertook a 3-year follow-up study of 1,090 people aged 60 and over, living in an urban area of Beijing. Prevalence rates of dementia, as defined by criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition (DSM-111; American Psychiatric Association, 1980), were between 1.28% (those aged 60 and over) and 1.82% (those aged 65 and over) in 1986 and 1.1% (those aged 65 and over) in VaD was more common than SDAT, with respective prevalence rates of 0.37% and 0.83%. The impressiveness of Li s low rates of dementia is tempered by the findings of Zhang and colleagues (1990). In their survey of 5,055 International Psychogeriatrics, 10(2), June 1998

5 Dementia and Ethnicity older community residents of Shanghai, Zhang and colleagues found the prevalence of dementia to be 4.6% for subjects aged 65 and over, a rate similar to that observed in Europe and the US. The authors used a two-stage research design, a screening phase followed by a comprehensive interview. Both Li and Zhangsuggested that the variations in rates of dementia were due to methodological and diagnostic differences rather than to actual differences. Kua (1991) used a stratified sample of 612 Chinese subjects aged 65 and over in Singapore to assess community rates of dementia. Kua used the semistructured interview schedule of the Geriatric Mental State (GMS; Copeland et al., 1976) to identify cases. The overall prevalence rate of dementia was l.8%, similar to that reported by Li and colleagues (1989) in China. Kua compared his data to that collected in Liverpool (Copeland et al., 1987) and found that the age of distribution of the patients with dementia in the two centers was similar; this result indicates that selective mortality was unlikely to be the cause of the difference. There was a higher rate of SDAT (1.14%) and a lower rate of VaD (0.7%). The use of the GMS and community sampling by Kua allows the direct comparison of his rates with those of Copeland s in Liverpool. The study appears to highlight a true difference in rates of dementia, but unfortunately the educational level of the Liverpool and Singapore participants was not provided and remains an uncontrolled confounding variable. Shibayama and colleagues (1986) surveyed a community-based Japanese population (3,106 persons aged 65 and over). Using diagnostic criteria that were in accordance with DSM-I11 and the ninth revision of the International Classification of Diseases (ICD-9; World Health 187 Organization, 1978), they found a prevalence rate of dementia of 5.8% (moderate and severe, 2.2%; mild 3.6%), again similar to Western rates. There was a 2.8% prevalence of VaD and 2.4% for SDAT. Possible cases were identified by trained community workers who obtained information on health status and social and domestic data, but no standardized method of identification was used and therefore selection bias cannot be ruled out. Shaji and colleagues (1996) undertook a community survey of people aged 60 and above in a rural area of Kerala (N = 2,067). Using diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-111-R; American Psychiatric Association, 1987) to define dementia cases and the 10th revision of the International Classification of Disease (ICD-10; World Healthorganization, 1992) to subcategorize the dementia, they found an overall prevalence rate of dementia of 3.4%, with 58% of cases due to VaD and 41% due to SDAT. The authors used sound techniques in sampling, identification of possible cases, and diagnosis; unfortunately, as the authors observed 161 of the original 2,191 subjects identified did not complete the screening and/or diagnosis phase, which can lead to data bias. Rajkumar and colleagues (1997) interviewed 750 elderly rural community-dwelling subjects (60 years and over) on the outskirts of Madras. The sample of 750 was drawn using cluster-sampling techniques. The authors used the GMS as a screening and diagnostic tool in the identification and diagnosis of dementia cases. They found prevalence rates of dementia Of 3.5% using clinician consensus but observed that the computer diagnostic system-automated Geriatric Examination Computer-Assisted Taxonomy (AGECAT)-developed for use with the GMS identified a number

6 188 of false positives. The main reason for the discrepancy was the ability of the clinicians to identify poor performance on the GMS due to low literacy levels. The clinician prevalence rates of dementia agree well with those of Shaji and colleagues (1996). DEMENTIA RATES IN AFRICA In 1991 and 1992, Osuntokun and colleagues claimed that there was an absence of any clinical, epidemiological, or neuropathological evidence of Alzheimer s disease in indigenous Black Africans. This statement was based on the results of two studies: an autopsy survey of brains of elderly Nigerians showing an absence of senile plaques and neurofibrillary tangles associated with SDAT, and a doorto-door survey of 9,000 people that included 932 elderly Nigerians who showed no clinical evidence of dementia as defined by DSM-111-R. Both studies have flaws in case identification methods. A retrospective survey of hospital files, to assess rates of mental disorders in a general hospital in western Ethiopia between the years of 1960 and 1970 (Jacobsson, 1985), seemed to confirm the rarity of Alzheimer s disease in Africa. Of 226 psychiatric admissions to the Amanuel Hospital in Addis Abeba between 1960 and 1970, only 2 fulfilled the World Health Organization classification for dementia senilis (0.009%). However, this study is obviously flawed by virtue of its retrospective nature and its hospital sample population. Further collaborative work between the University of Ibadan researchers, Osuntokun and colleagues, and Hendrie and colleagues (1995) did identify cases of SDAT in the Ibadan region of Nigeria. A comparative survey of 2,494 community C. Graham et al. residents in Ibadan, Nigeria, and 2,212 African Americans in Indianapolis, Indiana, was undertaken. The authors developed an educationally fair screening tool for dementia and the diagnosis of probable and possible Alzheimer s disease was based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association (NINCDS- ADRDA) criteria (McKhann et al., 1984). Sixty-five subjects in the US and 28 subjects in Nigeria met the ICD-10 and DSM- 111-R diagnostic criteria for dementia. Of the 65 subjects with dementia in the US, 49 had possible or probable SDAT (NINCDS-ADRDA criteria; McKhann et al., 1984) and 10 subjects had VaD (ICD- 10 criteria). Eighteen subjects in Nigeria had probable or possible SDAT and 8 had VaD. Age-adjusted prevalence rates of dementia were 2.29% for Ibadan and 8.24% for Indianapolis. In the US, 75% of cases were due to SDAT and 15% were due to vascular disease. In Nigeria, 64% of the dementia cases were due to SDAT and 29% were due to VaD. The authors indicated that despite all efforts to account for uncontrolled variables, cul tura1 bias in diagnosis could not be eliminated. They also observed that greater mortality in demented subjects in Ibadan could account for the differing prevalence rates. DISCUSSION Epidemiological surveys continue to imply that ethnic differences occur in rates of dementia. Lower rates of dementia occur in Nigeria, Singapore, and possibly China. India has rates of dementia at the lower range of rates shown in prevalence studies International Psychogeriatrics, 10(2), June 1998

7 Dementia and Ethnicity in Europe and the US. Japan appears to have prevalence rates of dementia at levels comparable to those in Europe and the US. In each center outside Europe and the US (except Singapore), VaD rather than SDAT predominates. National cross-cultural studies also identify ethnic differences, with African Americans experiencing not only higher rates of dementia than their African counterparts but also higher rates than the White American population. The quality of recent epidemiological surveys has been of a high standard, adding weight to the probability of ethnic differences in the rates of dementia, but no study to date has controlled for all six of the confounding variables mentioned at the beginning of this article; therefore, questions still remain as to the validity of these differences in rates. It is, at present, difficult to make inferences as to the etiology of these ethnic differences in rates of dementia; however, further light is shed on the matter by the recent studies into apolipoprotein E (ApoE; reviewed by Holmes, 1997). ApoE is a protein involved in the binding of lipoproteins to low-density lipoprotein receptors. ApoE has three major isoforms-apo-e2, apo-e3, and apo-e4- all encoded for by a single gene locus on chromosome 19. An increased frequency of ApoE-e4 allele occurs in late-onset familial AD (Strittmatter et al., 1993) to such an extent that someone with an e4/e4 genotype has a 43% probability of developing SDAT by the age of 85 years (Poirier et al., 1993). However, the relative risk that possession of this allele confers on the individual for developing dementia differs by ethnic group. Osuntokun and colleagues (1995) did not show an increase in the frequency of the ApoE-e4 allele in native Nigerians 189 with SDAT compared with nondemented individuals; this finding implies that possession of the ApoE-e4 allele by native Nigerians does not increase their relative risk of developing SDAT. Tang and colleagues (1996) studied a multiethnic population in Manhattan and showed that the relative risk was 7.3 for developing dementia in Whites homozygous for the ApoE-e4 allele, 2.5 for Hispanics, and 3.0 for African Americans. Therefore, the possession of the ApoE-e4 allele alone cannot account for the distribution rates of dementia. The ethnic differences in genetic expression of the gene allele indicate that the etiology of dementia probably lies in the realm of multifactorial risk factors, with the expression of genetic predisposition being moderated by environmental factors. Ethnic differences in rates of dementia both nationally, within multiethnic communities, and internationally have important repercussions for service delivery and offer opportunities for future research into possible etiological factors. The topic will therefore continue to be of interest to geriatric psychiatrists. The need for methodologically sound, cross-cultural comparative studies remains paramount. REFERENCES American Psychiatric Association. (1980). Diagnostic and statistical manual of mental disorders (3rd ed.). Washington, DC: Author. American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders (3rd ed.-rev.). Washington, DC: Author. Bachman,D. L., Wolf, P. A.,Linn, R., Knoefel, J., Cobb, J., et al. (1992). Prevalence of dementia and probable senile dementia of Alzheimer type in the Framinghani study. Neurology, 42, Beck, E., Daniel, P. M., Gadjusek, D. M., &k Gibbs, C. J. (1966). Experimental kuru in

8 190 chimpanzees. A pathological report. Lancet, 2, Bohnstedt, M., Fox, P. J., & Kohatsu, N. D. (1994). Correlates of Mini-Mental Status examination scores among elderly demented patients: The influence of raceethnicity. Journal of Clinical Epidemiology, 47, Copeland, J. R. M., Kelleher,M. J., Kellet, J. M., Gourlay, A. J., Gurland, B. J., et al. (1976). A semi-structured clinical interview for the assessment of diagnosis and mental state in the elderly: The Geriatric Mental Status Schedule. I: Development and reliability. Psychological Medicine, 6, Copeland, J. M., Dewey, M. E., Wood, N., Searle,R.,Davidson,A.,etal. (1987). Range of mental illness among the elderly in the community. Prevalence in Liverpool using the GMS-AGECAT package. British Journal of Psychiat y, 150, Copeland, J. M. R., Davidson, I. A., Dewey, M. E., Gilmore, C., Larkin, B., et al. (1992). Alzheimer s disease, other dementias, depression and pseudodementia: Prevalence, incidence and three-year outcome in Liverpool. British Journal of Psychiat y, 162, Essen-Moller, E. (1956). Individual traits and morbidity in a Swedish rural population. Acta Psychiatrica Scandinavica, Suppl. 100,l-160. Folstein, M. F., Anthony, J. C., Parhad, I., Duffy, B., & Gruenberg, E. (1985). The meaning of cognitive impairment in the elderly. Journal of the American Geriatrics Society, 33, Henderson, A. S. (1994). Epidemiology of mental disorders and psychosocial problems. Geneva, Switzerland: World Health Organization. Hendrie, H. C., Osuntokun, B. O., Hall, K. S., Ogunniyi, A. O., Hui, S., et al. (1995). Prevalence of Alzheimer s disease and dementia in two communities: Nigerian Africans and African Americans. American Journal of Psychiatry, 252, Heyman, A., Fillenbaum, G., Prosnitz, B., Raiford, K., Burchett, B., et al. (1991). Estimated prevalence of dementia among elderly black and white community residents. Archives of Neurology, 48, International Psychogeriatrics, 10(2), June 1998 C. Graham et al. Holmes, C. (1997). Apolipoprotein E: Implications and applications. In C. Holmes & R. Howard (Eds.), Advances in old age psychiatry (pp ). UK: Wrightson Biomedical Publishing. Jacobsson, L. (1985). Mental disorders in patients admitted to a general hospital in western Ethiopia Acta Psychia trica Scandinavica, 72, Jorm, A. F., Korten, A. E., & Henderson, A. S. (1987). The prevalence of dementia: A quantitative integration of the literature. Acta Psych ia trica Scandinavica, 76, Kahana, E., Alter, M., Braham, J., & Sofer, D. (1974). Creutzfeldt-Jakob disease: Focus among Libyan Je vs in Israel. Science, 183, Kua, E. H. (1991). The prevalence of dementia in elderly Chinese. Acta Psychiatrica Scandinavica, 83, Kurland, L. T., & Mulder, D. W. (1954). Epidemiological investigations of amyotrophic lateral sclerosis. Neurology, 4, , Lessell, S., Hirano, A., Torres, J., & Kurland, L. T. (1962). Parkinsonism-dementia complex. Archives of Neurology, 7, Li, G., Shen, Y. C., Chen, C. H., Zhao, Y. W., Li, S. R., et al. (1989). An epidemiological survey of age-related dementia in an urban area of Beijing. Acta Psychiatrica Scandinavica, 79, Li, G., Shen, Y. C., Chen, C. H., Zhau, Y. W., Li, S. R., et al. (1991). A three-year followup study of age-related dementia in an urban area of Beijing. Acta Psychiatrica Scandinavica, 83, Lin, T., Rin, H., Yeh, E.-K., Hsu, C.-C., & Chu, H.-M. (1969). Mental disorders in Taiwan, fifteen years later: A preliminary report. In W. Caudell and J. Lin (Eds.), Mental health research in Asia and the Pacific (pp ). Honolulu, HI: East-West Centre Press. Loewenstein, D. A,, Ardila, A., Rosselli, M., Hayden, S., Duara, R., et al. (1992). A comparative analysis of functional status among Spanish- and English-speaking patients with dementia. Journal of Gerontology, 47, Loewenstein, D. A., Arguelles, T., Barker, W. W., & Duara, R. (1993). A comparative

9 Dementia and Ethnicity analysis of neuropsychological test performance of Spanish-speaking and English-speaking patients with Alzheimer s disease. Journal of Gerontology, 48, Lyon, R. L. (1962). Huntington s chorea in the Moray Firth area. British Medical Journal, 1, McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., et al. (1984). Clinical diagnosis of Alzheimer s disease: Report of the NINCDS-ADRDA Work Group. Neurology, 34, Myrianthopoulos, N. C. (1966). Huntington s chorea. Journal of Medical Genetics, 3, Nielsen, J. (1962). Geronto-psychiatric period-prevalence investigation in a geographically delimited population. Acta Psychia trica Scandinavica, 38, Osuntokun, B. O., Ogunniyi, A. O., Lekwauwa, G. U., & Oyediran, A. B. (1991). Epidemiology of age-related dementias in the Third World and aetiological clues of Alzheimer s disease. Tropical and Geographical Medicine, 43, Osuntokun, B. O., Ogunniyi, A. O., & Lekwauwa, U. G. (1992). Alzheimer s disease in Nigeria. African Journal of Medicine and Medical Science, 21(2), Osuntokun, B. O., Sahota, A., Ogunniyi, A. O., Gureje, O., Baiyewu, O., et al. (1995). Lack of association between apolipoprotein E e4 and Alzheimer s disease in elderly Nigerians. Annals of Neurology, 38, Pittman, J., Andrews, H., Tatemichi, T., Link, B., Struening, E., et al. (1992). Diagnosis of dementia in a heterogeneous population; a comparison of paradigm-based diagnosis and physician s diagnosis. Archives of Neurology, 49, Poirier, J., Davignon, J., Bouthillier, D., Kogan, S., Betrand, P., et al. (1993). Apoprotein E polymorphism and Alzheimer s disease. Lancet, 342, Rajkumar, S., Kumar, S., & Thara, R. (1997). Prevalence of dementia in a rural setting: A report from India. International Journal of Geriatric Psychiatry, 12, Schoenberg, B. S., Anderson, D. W., & Haerer, A. F. (1985). Severe dementia: Preva- 191 lence and clinical features in a bi-racial US population. Archives of Neurology, 42, Shaji, S., Promodu, T., Abraham, T., Roy, K. J., & Verghese, A. (1996). An epidemiological study of dementia in a rural community in Kerala, India. British Journal of Psychiatry, 168, Shibayama, H., Kasahara, Y., Kobayashi, H., et al. (1986). Prevalence of dementia in a Japanese elderly population. Acta Psychiatrica Scandinavica, 74, Silverman, J. M., Li, G., Schear, S., Wang, Z. X., Sotolongo, C., et al. (1992). A crosscultural family history study of primary progressive dementia in relatives of nondemented elderly Chinese, Italians, Jews and Puerto Ricans. Acta Psychiatrica Scandinavica, 85, Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., et al. (1993). Apoprotein E: High avidity binding to beta-amyloid and increased frequency of type4 allele in late onset familial Alzheimer s disease. Proceedings of the National Academy of Science USA, 90, Tang, M. X., Maestre, G., Tsai, W. Y., et al. (1996). Relative risk of Alzheimer s disease and age-at-onset distributions based on APOE genotypes among elderly African Americans, Caucasians and Hispanics in New York City. American Journal of Human Genetics, 58, Teresi, J. A., Golden, R., Cross, P., Gurland, B., Kleiman, M., et al. (1995). Item bias in cognitive screening measures: Comparisons of elderly white, Afro-American, Hispanic and high and low education subgroups. Journal of Clinical Epidemiology, 48, Weissman, M., Myers, J. K., Tischler, G. L., Holzer, C. E., Leaf, P. J., et al. (1985). Psychiatric disorders (DSM-111) and cognitive impairment among the elderly in a US urban community. Acta Psychiatrica Scandinavica, 71, Zhang, M., Katzmann, R., Salmon, D., Tin, H., Cai, C. T., et al. (1990). The prevalence of dementia and Alzheimer s disease inshanghai, China: Impact of age, gender and education. Annals of Neurology, 27,