Gene/Stress Interaction Increases Cognitive Decline In Elderly

The negative effects of stress on cognitive functioning appear to be amplified by a genetic variation associated with Alzheimer's disease, a new federally funded study has found. The genetic variation may, in effect, accelerate the development of age-related cognitive decline by as much as eight years.

Researchers from the Baltimore Memory Study report in The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association, that a high level of the stress hormone cortisol in study participants aged 50 to 70 years was associated with worsened cognitive abilities. The researchers also found that the effect was greater among those with a common form of the gene for apolipoprotein E (APOE), which has been shown to increase the risk for Alzheimer's disease.

This gene-environment interaction is reported by Brian Lee, M.H.S., Brian Schwartz, M.D., and colleagues at Johns Hopkins University. The group's findings will be presented online on July 1 under AJP in Advance . The effect appears to increase as the number of copies of a specific APOE gene in the individual increases. Everyone inherits two versions of the APOE gene, known as alleles - one from each parent. The most common APOE alleles are epsilon-2, -3, and -4. Having at least one epsilon-4 allele increases an individual's risk of late-onset Alzheimer's disease. Individuals with two copies of the esiplon-4 version of the gene are particularly susceptible to the damaging effects of cortisol in the brain.

"Our findings indicate that the APOE epsilon-4 allele may increase vulnerability of the aging brain to elevated cortisol levels," said lead author Lee, a doctoral student in epidemiology at the Johns Hopkins Bloomberg School of Public Health. "While our results remain to be replicated, the observed cortisol-APOE interaction is intriguing since both cortisol and APOE have been implicated in cognitive decline associated with aging as well as in Alzheimer's disease."

The effects on cognitive functioning extended to six of the seven areas that were studied: language, eye-hand coordination, executive functioning, verbal memory/learning, visual memory, and ability to copy a complex visual design.

The deficits are similar in magnitude to those seen with advancing age. The authors estimated the equivalent years of increased age, represented by the poorer cognition of the study participants with high cortisol and the epsilon-4 form of the APOE gene. For language ability, the lower scores of people with high cortisol levels and one epsilon-4 copy were comparable to an age increase of eight years. For those with two epsilon-4 copies, the comparable age increase was even larger.

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