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Apolipoprotein E Polymorphism and Alzheimer Disease
The Indo-US Cross-National Dementia Study
Mary Ganguli, MD, MPH;
Vijay Chandra, MD, PhD;
M. Ilyas Kamboh, PhD;
Janet M. Johnston, PhD;
Hiroko H. Dodge, PhD;
B. K. Thelma, PhD;
Ramesh C. Juyal, PhD;
Rajesh Pandav, MBBS;
Steven H. Belle, PhD;
Steven T. DeKosky, MD
Arch Neurol. 2000;57:824-830.
Background The APOE*E4 allele of the gene for apolipoprotein E (APOE) has been reported as a risk factor for Alzheimer disease (AD) to varying degrees in different ethnic groups.
Objective To compare APOE*E4-AD epidemiological associations in India and the United States in a cross-national epidemiological study.
Design Case-control design within 2 cohort studies, using standardized cognitive screening and clinical evaluation to identify AD and other dementias and polymerase chain reaction to identify APOE genotyping.
Participants Rural community samples, aged 55 years or older (n=4450) in Ballabgarh, India, and 70 years or older (n=886) in the Monongahela Valley region of southwestern Pennsylvania.
Main Outcome Measures Criteria of the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association for probable and possible AD and Clinical Dementia Rating (CDR) scale for dementia staging.
Results Frequency of APOE*E4 was significantly lower (P<.001) in Ballabgarh vs the Monongahela Valley (0.07 vs 0.11). Frequency of probable or possible AD, with CDR of at least 1.0, in the Indian vs US samples, was as follows: aged 55 to 69 years, 0.1% (Indian sample only); aged 70 to 79 years, 0.7% vs 3.1%; aged 80 years or older, 4.0% vs 15.7%. Among those aged 70 years or older, adjusted odds ratios (95% confidence interval) for AD among carriers of APOE*E4 vs noncarriers were 3.4 (1.2-9.3) and 2.3 (1.3-4.0) in the Indian and US samples, respectively, and not significantly different between cohorts (P=.20).
Conclusion This first report of APOE*E4 and AD from the Indian subcontinent shows very low prevalence of AD in Ballabgarh, India, but association of APOE*E4 with AD at similar strength in Indian and US samples.
From the Division of Geriatrics and Neuropsychiatry, Department of Psychiatry, and Alzheimer's Disease Research Center, University of Pittsburgh School of Medicine (Drs Ganguli and DeKosky), and the Departments of Epidemiology (Drs Ganguli, Chandra, Johnston, Dodge, Pandav, and Belle) and Human Genetics (Dr Kamboh), University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pa; and the Centre for Ageing Research in India (Drs Chandra and Pandav), the Department of Genetics, University of Delhi South Campus (Dr Thelma), and the National Institute of Immunology (Dr Juyal), New Delhi, India.
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