Gene interacts with hormone to impair thinking

NEW YORK (Reuters Health) - A variation of a gene called apolipoprotein E (APOE) affects how the stress-related hormone cortisol influences the thinking or "cognitive" ability in older adults, according to a report in the American Journal of Psychiatry.

In particular, the E4 version of the gene, which is a well-known risk factor for Alzheimer's disease, increases the cognitive impairment seen with high cortisol levels. In response to stress, cortisol also increases blood pressure and blood sugar levels and suppresses the immune system. High cortisol levels may be indicative of a number of diseases.

In a study of 967 older adults, Dr. Brian S. Schwartz and colleagues, from Johns Hopkins University in Baltimore, found that higher levels of cortisol in saliva were associated with worse cognitive performance. Their current study investigated the same group of subjects, but now included data on the APOE type.

Cognitive testing focused on a variety of functions, including language ability and memory. Cortisol levels were measured in saliva samples obtained before, during, and after cognitive testing, and blood samples were also used to test for APOE.

In subjects with normal cortisol levels, the presence of one or two copies of the E4 version of APOE (everyone has two copies of a gene, which may be present in different variations) did not worsen cognitive ability.

By contrast, in persons with high cortisol levels, one copy of the E4 version of the APOE gene impaired several cognitive abilities. With two copies of E4, all cognitive abilities were worsened.

These findings are plausible, given the wide distribution of cortisol receptors throughout the brain and the influence of APOE on multiple aspects of brain activity, Schwartz and his associates note.

The findings suggest that APOE influences cortisol's effect on cognitive function and that the E4 version makes the aging brain more vulnerable to the adverse effects of stress, they conclude.

SOURCE: American Journal of Psychiatry, online July 1, 2008.