Older people with the ’Alzheimer’s gene’ find it harder to ’remember to remember’ even if healthy

Study finds surprisingly strong impact of genetic variation

Carrying the higher-risk genotype for Alzheimer’s disease appears to render even healthy older people subject to major problems with prospective memory, the ability to remember what to do in the future. For the group studied, this could affect important behaviors such as remembering to take medicine at a certain time or getting to a doctor’s appointment. The research appears in the January issue of Neuropsychology, which is published by the American Psychological Association.

People with this genotype have a certain variety, or allele, of a gene called ApoE (for Apolipoprotein E), which switches on production of a protein that helps carry cholesterol in the blood. ApoE has three alleles and about one out of five people carry the e-4 allele. It makes homozygous carriers, who carry this variation on both of their ApoE genes, eight times as likely to develop Alzheimer’s disease as non-carriers. Heterozygous carriers, who carry the high-risk variation only on half the pair, have a three-fold higher risk. Neuro- psychologists have looked at the episodic, or retrospective, memory, of e-4 carriers, especially for recent events. This study was the first to look at their prospective memory.

At the University of New Mexico, a group of 32 healthy, dementia-free adults between ages of 60 and 87 were drawn from a larger study of aging and divided evenly between people with and people without the e-4 allele.

On a task in which participants were asked to remember to write a certain word when they saw a target word, the carriers showed significantly worse prospective memories. Far more often than non-carriers, they failed to remember to write down the desired word when they were supposed to – in other words, they forgot to do what they meant to do, when they meant to do it.

Because the Alzheimer’s genotype had a strong and obvious effect on prospective memory, the study’s authors recommend changing the prevailing view that the allele has only subtle, often undetectable effects on cognition. The findings also supplement previous discoveries of how the allele also is linked to problems in episodic retrospective memory, even without any signs of dementia.

Given these findings, clinicians can help even healthy e-4 carriers to improve their prospective memory. Having been found to be an important “exception to the rule” about the impact of this genetic variation, prospective memory appears to merit more research.

What’s more, co-author Mark McDaniel, PhD, says that “Our results might provide some encouragement to the use of prospective memory as an early diagnostic tool” because other research has found a steep prospective-memory drop in patients with very mild disease. He explains, “Our sample of carriers were healthy as far as we could tell, but our assessments were not as sensitive as some of those used at the major Alzheimer’s research centers. It might well be that some of our carriers were in early AD stages that were not yet detected.”

Replicating the results on a different group of people, using ultra-sensitive tests, could result in the promise of a simple test to aid in early diagnosis of Alzheimer’s disease.

Finally, McDaniel points out that major problems with prospective memory could alert older adults to the presence of a genetic risk for Alzheimer’s. He says, “It could be useful for someone to recognize such a risk, as recent research suggests that lifestyle factors such as diet, including cholesterol, may be important in the development of the disease precisely for those with the genetic predisposition.”