The 4 variant of the apolipoprotein E (APOE) gene contributes to the risk for memory loss related to Alzheimer's disease. Similarly, high circulating levels of cortisol, associated with high stress levels, also impairs memory. However, the interactive effects of this risk genotype and chronic stress are not well understood, so a new study being published in the September 1st issue of Biological Psychiatry was designed to explore this relationship.

In their study, Peavy and colleagues performed genotyping and measured the chronic stress level in 91 older, healthy subjects (mean age was 78.8 years). Those low on stress or without the APOE- 4 risk factor performed better on memory measures than those with high stress or those positive for APOE- 4, respectively. Those individuals experiencing high stress and who were positive for APOE- 4 showed the greatest memory impairment.

One of the authors, Guerry M Peavy, Ph.D., comments, "Perhaps the most interesting result of the study was the interaction we found between genetic status and the experience of high stress events. That is, for some aspects of memory, highly stressful experiences had a detrimental effect only on those individuals who carried the APOE- 4 allele.

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, adds:

This is a very exciting time in Alzheimer's disease (AD) research The findings of Peavy et al. suggest that environmental factors, like chronic stress, may interact with an AD risk genotype, APOE- 4, to promote age-related memory impairment. These data raise the possibility that psycho-social interventions and psychotherapeutic medications might enhance the effectiveness of medication treatment strategies aimed at preserving memory function in older adults.

As noted in their article, because APOE- 4 status and high stress levels can be assessed at any time, these findings may represent an advantage with the earlier identification of elderly individuals who do not yet meet criteria for dementia, but who clearly are more cognitively vulnerable. Dr. Peavy explains, The results of the study have implications for interventions that could prevent harmful responses to stressful experiences and, as a result, could prevent or slow the progression of cognitive changes in genetically vulnerable, older individuals. For now, longitudinal studies need to be undertaken to determine if these interactive effects of stress and APOE- 4 status become predictors of a clinical diagnosis of dementia.

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