SAN FRANCISCO—Several decades of data are finally helping medical science clarify how four variables—race, genetics, the environment, and heart disease—affect an individual’s chance of developing Alzheimer’s disease. A major source of the data is the Charleston Heart Study, in which a random population sample of 2,181 African-Americans and whites in Charleston, South Carolina, were followed for nearly 30 years.

Investigators found that a history of coronary artery disease increased the risk of cognitive decline in African-Americans and whites, although the association was weak in the latter group and quite robust in the former. These findings are similar to those of other studies suggesting that lipid-lowering drugs may reduce the risk of cognitive decline related to Alzheimer’s disease.

Together, the available data support the assertion that “what is good for the heart is good for the brain,” said Jacobo E. Mintzer, MD, at the 156th Annual Meeting of the American Psychiatric Association. Dr. Mintzer is Codirector of Alzheimer’s Research and Clinical Programs and Professor of Psychiatry and Neurology at the Medical University of South Carolina in Charleston.

FINDINGS FROM THE CHARLESTON HEART STUDY

The subjects of the Charleston Heart Study, who were 35 or older at the study’s 1960 inception, underwent regular evaluations, which included the Short Portable Mental Status Questionnaire and Russell’s Revision of the Wechsler Memory Scale, during the next several decades. The researchers obtained baseline values for those two cognitive measures in 1987 and 1989 and follow-up results in 1991 and 1992.

At follow-up, whites with coronary artery disease had an odds ratio of 1.7 for a loss of immediate visual memory. A history of coronary artery disease was also weakly linked to drops in delayed and immediate visual recall in whites. However, African-Americans with coronary artery disease had an odds ratio of 2.6 for a loss of immediate visual memory. That group also showed strong negative associations between a high body mass index and delayed verbal memory, coronary artery disease and immediate and delayed visual memory, hypertension and immediate visual memory, and high total cholesterol and delayed visual memory.

The greatest cognitive losses occurred among African-American men of high socioeconomic status, who exhibited decreases of about 70% in both immediate and delayed verbal memory at follow-up. By comparison, African-American men who were not of high socioeconomic status demonstrated declines of about 55% and 50% in those cognitive measures.

THE IMPACT OF ENVIRONMENT

The environment may be a factor in the development of dementia and Alzheimer’s disease, because rates of those conditions are noticeably different among African-Americans and black populations of Africa such as the Yoruba of West Africa. African-Americans have an overall dementia rate of 3.24%. In comparison, the Yoruba have a dementia rate of only 1.35%.

“The big difference is in Alzheimer’s disease. [There is] 2.5 times the amount of Alzheimer’s disease in African-Americans as there is in the Yoruba,” said Hugh C. Hendrie, MD. Dr. Hendrie is Codirector of the Center for Alzheimer’s Disease and Related Neuropsychiatric Disorders and a Professor of Psychiatry at the Indiana University School of Medicine in Indianapolis.

GENES, THE ENVIRONMENT, AND OTHER HEALTH FACTORS

The environment may interact with genetics to affect the risk of Alzheimer’s disease, and one particularly important genetic variable appears to be the apolipoprotein E (APOE) epsilon4 genotype. “If you have one of these APOE epsilon4 alleles, your risk of developing Alzheimer’s disease increases by two to three times,” explained Dr. Hendrie. “If you unfortunately have two of these alleles, it increases by eight to 12 times.”

Dr. Hendrie noted that a strong association between APOE epsilon4 and Alzheimer’s disease is prevalent around the world, including in Europe, Asia, Latin America, Australia, North America, and Africa. However, the influence of APOE epsilon4 on the risk of Alzheimer’s disease is uncertain in nonwhite Hispanics, weak in African-Americans, and not present in Nigerians and Kenyans.

At 3% to 5%, the frequency of APOE epsilon4 is comparatively low in the Amish, and at up to 40% it is particularly high in some aboriginal populations. The allele’s frequency is 8% in the Japanese, 11% to 16% in whites, 24% in the Finnish, and 23% to 25% in African-Americans, Dr. Hendrie also reported.

In African-Americans, APOE epsilon4 appears to interact with cholesterol levels to determine the risk of Alzheimer’s disease. In those with high cholesterol, the risk is not elevated if they have the allele, whereas those who do not have it are at significantly increased risk.

NR

—Timothy Begany

Suggested Reading
Bennett DA, Wilson RS, Schneider JA, et al. Apolipoprotein E epsilon4 allele, AD pathology, and the clinical expression of Alzheimer’s disease. Neurology. 2003;60:246-252.
Graff-Radford NR, Green RC, Go RC, et al. Association between apolipoprotein E genotype and Alzheimer disease in African American subjects. Arch Neurol. 2002;59:594-600.
Hendrie HC, Ogunniyi A, Hall KS, et al. Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, Indiana. JAMA. 2001;285:739-747.
Tan ZS, Seshadri S, Beiser A, et al. Plasma total cholesterol level as a risk factor for Alzheimer’s disease: the Framingham study. Arch Intern Med. 2003;163:1053-1057.

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