Gene/Stress Interaction Increases Cognitive
Decline In Elderly
July 1, 2008
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.
The study was supported by the National Institute on Aging and the National
Institutes of Health Division of Research Resources.
Reference
Lee BK, Glass TA, Wand GS, McAtee MJ, Bandeen-Roche K, Bolla KI, Schwartz BS:
Apolipoprotein E Genotype, Cortisol and Cognitive Function in Community-Dwelling
Older Adults. Am J Psychiatry (published online July 1, 2008; doi:
10.1176/appi.ajp.2008.07091532)
About the American Journal of Psychiatry
The American Journal of Psychiatry is the official journal of the
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articles in the Journal are not official policy statements of the
American Psychiatric Association. AJP in Advance is a regular online
feature where original research articles accepted for publication in The
American Journal of Psychiatry are posted online in advance of their
appearance in print.
About the American Psychiatric Association
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whose more than 38,000 physician members specialize in diagnosis, treatment,
prevention and research of mental illnesses including substance use disorders.
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