155 Epidemiology of dementia in elderly Chinese — a cross-national comparison of Singapore and Beijing

FIFTH INTERNATIONAL CONFERENCE ON ALZHEIMER'S DISEASE homeostasis and AI3 sensitivity. It seems that these molecules are enriched in synaptic structure, interact with AI3, are a major regulator of synaptic plasticity and are genetically associated with Alzheimer's disease. We will present morphological, biochemical, cell biological and genetic data that argue their involvement in regulation of neuronal homeostasis and in the pathophysiology of Alzheimer's disease.

$39

BBB in human brains. Biopsy specimens obtained during neurosurgical procedures (for tumors and dementia) were used. Despite their small size being a limiting factor for detection of the above-mentioned regional differences in BBB function in experimental mice, these specimens appeared to be more adequate than autopsy material, in which post-mortem changes (coagulation of blood plasma and shrinkage or swelling of the eudothelium) make difficult the proper interpretation of the obtained results. (Supported in part by NIH/NIA, grant RO1-AG 10279-05).

152 AMYLOID 15 PROTEIN AND THE CEREBROVASCULAR PATHOLOGY IN ALZHEIMER'S DISEASE R.N. Kalaria, H. Mori* and P Hedera. Departments of Neurology and Pathology, and the UH Alzheimer Center, Case Western Reserve University, Cleveland, Ohio 44106, USA; *Tokyo Institute of Psychiatry, Tokyo 154, Japan. The integrity of the brain vasculature is crucial to the maintenance of cognitive functions during aging and disease. Prevailing evidence suggests that cerebrovascular functions decline during normal aging with pronounced effects in both sporadic and familial Alzbeimer's disease (AD). The primary causes of these changes remain unknown. It is possible that amyloid g (AB) protein is involved in the degeneration of both the larger resistance vessels as well as the cerebral capillaries that represent the blood-brain barrier (BBB). We used immunochemicaland in vitro labelling methods to examine patterns of Ag deposition and production, and morphology of the cerebral endothelinm and basal lamina (BL) in relation to deposition of forms of Ag and apolipoprotein E in AD and non-AD aging control subjects. Double immunostaining with antibodies to vascular markers, revealed absence of endothelial staining in many capillary profiles that appeared to retain their BLs. Such differential labelling suggested capillaries with attenuated or degenerated endothelium that were largely restricted to the neocortex and lacking in brain regions free of Aft deposits. Quantitative studies showed that these microvascular abnormalities were related to AB deposition rather than neurofibrillary tangles or neuronal number. Further assessment of the abnormalities and amyloid infiltrated cerebral vessels with antibodies to the carboxyl terminus of Ag indicated that the longer form of Ag (1-42) was found to be predominantly associated with the degenerative process. This was also apparent in the larger cerebral vessels where Ag(1-42) positive myocytes were often evident, particularly in subjects with intracerebral hemorrhage. Our studies suggest that AB, irrespective of its origin within vascular myocytes or brain parenchyma, is responsible not only for cerebral amyloid angiopathy but degeneration of the cerebral microvasculature which may promote further cellular injury with widespread functional effects. Supported by grants from NIH (NIA) and ADRDA.

153 Blood-Brain Barrier (BBB) to Endogenous Albumin in Experimental and Naturally Occurring Neurodegenerative Diseases A.W. Vorbrodt* and D.H. Dobrogowska. NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York, 10314, USA. The presence of serum proteins in the parenchymal amyloid deposits found in the brain in Alzbeimer's disease and related disorders has been reported by some authors. These observations ~uggest that increased permeability of brain microvessels can be favorable for the development of neuropathological changes, including amyloid angiopathy and formation of amyloid plaques. To study this problem, we applied a quantitative immunocytochemical procedure that enables evaluation of the barrier function of brain microvasculature to albumin. Scrapie-infected mice of different scrapie strain mouse strain combinations, represented by two experimental groups--plaqueforming (PF) and non-plaque-forming (NPF)--were used as an animal model. Morphometric and statistical analysis of the distribution and density of immunosignals for albumin revealed insignificant differences in the barrier function of the microvasculature of the cerebral cortex in both animal groups. In contrast, in the hippocampus and especially in the cerebellum, the permeability of the microvessels to albumin was significantly higher in the PF than in the NPF group. These data also indicate the existence of distinct regional differences in BBB function in the brain of scrapie-infected mice, presumably related to the formation of amyloid deposits. Numerous immuuosignals scattered over the amyloid deposits in plaques and in the vessel wall (amyloid angiopathy) indicate the presence of extravasated blood plasma albumin in these areas. Because no foreign maeromolecular tracers are introduced into the blood circulation in the applied procedure, it can also be used for evaluation of the

SYMPOSIUM: EPIDEMIOLOGY FACTORS I

& RISK

154 Prevalence and Subtypes of Dementia in Taiwan and Kinmen H.C Liu , J.L; Fuh, S.J. Wang, E.B. Larson, E.L. Teng Neurological Institute, Veterans General Hospital-Taipei, Taiwan; Department of Medicine, Epidemiology and Health Services, University of Washington, Seattle; Department of Neurology, University of Southern California School of Medicine, Los Angeles, U.S.A. We studied the prevalence and subtypes of dementia among the Chinese in Taiwan (1988-89) and Kinmen (1993). In the Taiwan study, 5,297 individuals (2,753 men and 2,544 women), aged 41-88 years, from four urban and four rural communities participated; 28% of them were >= 65 years in age, and 27% of them had less than one year of formal schooling. Phase I was a screening survey using a Chinese version of the Mini-Mental State Examination, MMSE-T1. Phase II was assessment for dementia by neurologists, according to the DSM-III-R criteria, on individuals who had scored < 24 on the 30-point MMSE-T1. Thirty-one cases (15 men and 16 women) of dementia were identified, including 18 cases (58%) of Alzheimer's disease (AD) and 10 cases (32%) of vascular dementia (VD). The prevalence of dementia among individuals aged >= 65 was 2.0%. Older age and illiteracy were associated with higher rates of dementia. The Kinmen study was conducted in a single phase in which neurologists interviewed and examined all 1,736 (755 men and 981 women) participants aged >= 65 years, among whom 70% had < 1 year of formal schooling. The diagnosis of dementia was also made according to the DSMIII-R criteria and included consideration of performance on a Chinese version of the Cognitive Abilities Screening Instrument, CASI C-2.0, administered by research assistants. Forty-four cases (13 men and 31 women) of dementia were identified, including 35 cases (80%) of AD and 3 cases (7%) of VD. The prevalence of dementia among individuals aged >= 65 was 2.5%. Older age and illiteracy were associated with higher rates of dementia. In conclusion, the prevalence rates of dementia were low in these two Chinese populations; higher rates of dementia were associated with older age and illiteracy. AD was the most frequent subtype of dementia.

155 Epidemiology of Dementia in Elderly Chinese - a Cross-National Comparison of Singapore and Beijing

E. H. Kua Department of Psychological Medicine, National University Hospital 5 Lower Kent Ridge Road, Singapore 119074 Y. C. Shen Institute of Mental Health, Beijing Medical College Beijing, People's Republic of China This paper compares the prevalence of dementia in elderly Chinese living in Singapore and Beijing. The studies were conducted using similar i n t e r v i e w schedule, the Geriatric Mental State (Copeland et a11976), and similar diagnostic criteria the DSM IIIR.

$40

FIFTH INTERNATIONAL CONFERENCE ON ALZHEIMER'S DISEASE

In Singapore, a random sample of 804 Chinese aged 65 years and more, l i v i n g in t h e c o m m u n i t y , w a s i n t e r v i e w e d by psychiatrists. In Beijing. the initial screening nf 1331 subjects aged 60 years and more, was done using the Mini-Mental State Examination (MMSE) with a cutoff of 17 points. All suspected cases of dementia and 5 . 5 % o f all others were then assessed w i t h the Geriatric Mental State schedule. The prevalence of moderate and severe dementia in Beijing was 1.82% for those aged 65 and more. The rate for multi-infarct dementia was higher than that of Alzheimer's disease. In Singapore the prevalence of dementia was 2.5%. The rate for Alzheimer's disease was higher and multi-infarct dementia lower in Singapore than in Beijing.

156 Protective factors for cognitive decline in a Japanese American community. A.B. Graves*a, E.B. Larson2, A. Wenzlow~. 1University of South Florida, Tampa, FL, USA. 2University of Washington, Seattle, WA, USA. 3Battelle Memorial Institute, Seattle, WA, USA. Recently, several factors have been implicated as being protective for cognitive impairment (CI) and Alzheimer's disease (AD), including higher educational and occupational attainment, income, smoking and estrogen replacement use in women. The Kame Project is a community-based study of 1,985 Japanese Americans living in King County, WA, and one of three sites in a cross-cultural study of aging in Japanese populations in Hiroshima, Japan and Oahu, Hawaii. A prevalence survey of dementia was conducted in King County between 1992-1994. The Cognitive Abilities Screening Instrument, CASI, was used to screen for dementia; extensive risk factor interviews also were administered at baseline. Two years following the baseline interview, 1,035 persons were rescreened with the CASI by November 15, 1995. Of these, 110 had declined by 4.25 CASI points (mean change in the cohort minus one standard deviation) or more over the two year period. We performed logistic regressions predicting decline 24.25 points, adjusting for age and baseline CASt score. Good performance on the National Adult Reading Test (NART) in a subsample of 359 English-speakingsubjects was inversely associated with twoyear decline (OR for increase in one error=1.06 (95% CI: 1.02-1.10)), as were being born in Japan (Ol1.=.31, .12-.80), taking the baseline interview in Japanese (0R=.33, .15-.72) scoring fewer errors on a computerized test of reaction time (OR=.95, .90-.98), speaking Japanese at home (OR=.24, .09-.63), currently reading and writing Japanese with no difficulty(OR=.28,. 13-.59), and being educated in Japan (OR=.49, .28-.86). Sex, low education, income and occupational status did not predict decline in this sample; nor did low mother's or father's educational or occupational attainment. Ever having been on hormone replacement therapy was not inversely related to the risk of decline, and smokers were more likely to decline compared to non-smokers (OR=1.55, 1.03-2.34). Preservation of Japanese lifestyle may protect against cognitive decline over 2 years, and possibly against AD.

157 An Epidemiological Study of the Dementias in Cambridge: from Clinical Progression to Neuropathology C. Brayne*, F. A. Huppert, J. Xuereb, H. Gertz, L-Y. Chi, M.A. McGee, E. S. Paykel, C. Harrington, E. MukaetovaLadinska, A. O'Sullivan, C. Wischik Departments of Community Medicine, Psychiatry, and Pathology, University of Cambridge, United Kingdom In the mid to late eighties a large population survey of people aged 75 years and over was undertaken by O'Connor and colleagues in Cambridge city, UK. This provided estimation of the prevalence of dementia and formed part of the EURODEM group of dementia prevalence studies. The non-demented population was followed a little over two years later and the incidence of dementia, clinically diagnosed subtypes and cognitive decline as measured by MMSE has been reported. In this presentation further follow-up of this population will be reported. Diagnostic stability from the incidence phase, in those diagnosed as clinically demented (including minimal) will be

shown. Cognitive decline in those interviewed on three occasions will be described, including the relationship to baseline variables. Results from the parallel study of brains from individuals who gave premortem permission for autopsy will be included to describe the relationship of CAMDEX diagnoses to CERAD neuropathological categorisation, as well as neuropathological lesions which are related to cognitive decline in the total population.

158 Genetic and Environmental Causes of Alzheimer's Disease in Twins J.C.S. Breitner*, K.A. Welsh, J.M. Meyer and J.C. Anthony Department of Psychiatry, Duke University Medical School, Box 3925, Durham, NC 27710, USA Twin studies of complex disorders such as Alzheimer's disease (AD) can reveal both genetic and environmental influences. As known genetic loci such as APOE (the polymorphle locus for apolipoprotein E) are discovered, these may be incorporated into "partitioned twin analyses". Such analyses can assess the contribution of these and other, as yet unknown loci to phenotypic variation. Partitioning also permits co-twin control investigations of gene-environment interaction whereby environmental risk factors influence disease risk associated especially with certain vulnerable genotypes. In 1990-91 and again in 1993-94, we screened the NAS-NRC panel of 5,000 pairs of aging white male veteran twins for Alzheimer's disease, discovering over 60 probands. Because the panel was born between 1917 and 1927, only relatively early-onset instances (< age 75) of AD were discovered. Thus, we had little power to detect environmental factors that del~ty onset associated particular genotypes at APOE (although these factors should be readily demonstrable in older samples). In the NAS panel, heritability of AD was low (h2=.37), even in analyses that adjusted for the age of the sample. Surprisingly, 40% of cases had no e4 allele at APOE and no family history of AD; all their twin brothers remained unaffected, most for more than 10 years (mean period of discordance 13 years). These cases thus appear to have strong environmental provocation; their disease type appears to represent 6% 10% of all AD in the U.S. Preliminary analyses suggest that head injury and history of chronic allergic conditions are risk factors in this group.

159 Change of Prevalence Rates of Dementia in Tokyo Metropolis A. Homma*l), R. Niina 1), S. SakataI), T. Ishii l), K. Kawashima2), J. Sato2), E. Higuchi2), S. Wakutsu3), S. Higuchi2), H. Kasahara3), H Nishimura3>, H. Nakano 3), T. Shinozakia), T. Wakejima5), K. Niisato 5) ,K. Kase~), T. Fujishima 5), K. Ikeda6), S. Togo7), K. Koyamas), and O. Asakawa s) l) Department &Psychiatry, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173 Japan, 2)Department of Psychiatry, Sobu Hospital, 3) Department of Psychiatry, Jikei University School of Medicine, 4) Department of Psychiatry, Atsugi Prefectural Hospital, 5) Department of Psychiatry, Kashiwa Hospital, Jikei University School of Medicine, 6) Tokyo Metropolitan Institute of Psychiatry, 7~Department of Psychiatry, Tama Geriatric Medical Center, 8) Department of Psychiatry, Tokyo Metropolitan Geriatric Medical Center In comparing the results of large-scale epidemiological surveys in Tokyo metropolis in 1980 and in 1988, it was disclosed that the prevalence rates of dementia and its severity were reduced among elderly people living at home. It might be suggested that the decrease in the prevalence and incidence rates of age-associated dementia, especially of vascular dementia, actually had taken place during these period in Tokyo. The purpose of the present study was to examine and to confirm the above change of the prevalence rates of dementia in Tokyo metropolis. Randomly selected five thousand elderly people with the age more than 65 years among approximately 1,500,000 elderly inhabitants in Tokyo were