Disclosure of APOE Genotype Affects Memory Performance

The phrase “ignorance is bliss” can be applied to those who know—or do not know—what their genes say about their risk for Alzheimer’s disease (AD) and dementia. A study published October 30, 2013, in AJP in Advance showed how one’s knowledge of genetic status regarding the apolipoprotein E epilson 4 (APOE e4) allele—a suggested risk factor for neurocognitive decline—may have adverse consequences for one’s self-perception of memory.

Researchers from Butler University and the University of California, San Diego, conducted a study investigating the risks and benefits of disclosing APOE genotype to older adults as it relates to subjective and objective memory performance.

“I have long been interested in factors that influence many patients’ complaints concerning memory,” said lead author Tara Lineweaver, Ph.D., an associate professor of psychology at Butler. “Memory self-perceptions are playing a larger role in the diagnosis of mild cognitive impairment, so knowing how risk for Alzheimer’s disease affects subjective memory is an important issue.”

According to Lineweaver, several studies have investigated how being at risk for AD affects older adults’ self-perception of memory, but these studies used the family history of AD onset as the primary risk factor—not genetic risk variables such as APOE genotype.

APOE was first recognized for providing protection to the vasculature system by removing excess cholesterol from the blood. It was later found to enhance the breakdown of beta-amyloid in neurons—thereby, protecting the brain from neurocognitive decline. Mutated isoforms of the APOE gene, such as APOE e4 allele, are less protective and ineffective in catabolizing beta-amyloid.

“The link between APOE genotype and memory is well established, but our study suggests that the knowledge of that genetic risk may contribute to decline in objective memory and alter one’s subjective self-rating of memory.

“Our study used genotype to define risk for Alzheimer’s disease, which allowed us to separate whether or not someone was at risk for dementia from his or her personal knowledge of that risk,” Lineweaver said.

To test how knowledge of APOE genotype affected self-rating of memory abilities, Lineweaver and colleagues recruited 144 cognitively normal adults aged 52 to 89. Participants were genotyped for the APOE e4 allele and were divided into two groups—those who possessed the variant (e4+) and those who did not (e4-). APOE genotype status was disclosed to half of the participants in each group. All subjects were required to complete two self-assessment questionnaires of memory functioning, as well as objective verbal and visual memory tests.

Results showed that adults with the e4+ genotype who knew their status judged their memory more harshly and performed worse on the objective verbal memory test than e4+ genotype subjects who were unaware of their status. In contrast, those who knew of their e4- genotype judged their memory more positively than those who did not know their e4- genotype status. There was no difference in objective memory test scores in those who did not possess the APOE e4 allele.

“This is the first study to show that having knowledge of an increased genetic risk for Alzheimer’s disease can adversely influence one’s self-perception of memory ability and performance on objective memory tests,” said David Salmon, Ph.D., senior study author and a professor of neurosciences at UCSD.

He said in an interview with Psychiatric News that these findings could be applicable to other populations who are conscious of their genotype status for other biomarkers associated with an increased risk for AD and dementia that can be assessed by brain scan or cerebrospinal fluid analysis.

As science advances and people become more aware of their genetic risk for certain illnesses, it may be crucial for clinicians to know if their patients are aware of their genetic risk for AD, Salmon suggested. He emphasized that knowledge of genetic risks could influence the patient to be more sensitive to minor lapses of memory or be more “fatalistic” when performing memory tests, which was demonstrated in the current study.

“This could lead to a false-positive diagnosis of dementia or mild cognitive impairment in a patient who may actually stay cognitively intact,” he concluded.

The study was funded by the National Institute on Aging and the Alzheimer’s Center of California. ■