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Loss Of Memory In Middle Age Indicates Risk Of Alzheimer’s Disease Later

A study found that memory loss due to aging may be a predictor for Alzheimer's disease in later stages.

The study findings reported by Arizona Alzheimer’s Consortium team may help predict the effective future Alzheimer’s treatments, if started in middle-aged people.

In the study, 815 healthy participants of age 21 to 97 years were followed up for 14 years. The team conducted a sensitive memory and thinking tests to detect, track and compare cognitive performance, with two copies, one copy and no copies of the APOE e4 gene, the major genetic risk factor for developing Alzheimer’s disease at older ages. Each additional copy of this gene is linked to a higher risk of Alzheimer’s disease and a slightly younger age at the onset of clinically significant memory and thinking problems.

The study found that nearly one out of four people have one copy of the APOE e4 gene, which was inherited from one parent, and about 2 percent have two copies, which were inherited from both parents.

We found that memory declines begin to differentiate groups of people at these three levels of genetic risk starting between ages 55 and 60, years earlier than previously suspected, and well before the anticipated onset of clinically significant symptoms, said Richard J. Caselli, M.D., Chair of Mayo Clinic’s Neurology Department in Arizona and lead author of the research study. While other age-sensitive cognitive skills also change, memory, specifically, appears to decline more quickly in APOE e4 gene carriers, and it is this pattern of cognitive aging that is similar to (but much milder than) what we expect to see in patients with Alzheimer’s disease. This suggests that seemingly normal age-related memory loss may actually represent very early, preclinical-stage Alzheimer’s disease.

The researchers used brain-imaging techniques and reported brain changes in people at three levels of genetic risk, some of which appear decades before the onset of symptoms. The team explained the importance of conducting prevention trials starting in late middle-age, and also suggested how brain-imaging techniques could be used to evaluate these treatments without having to study thousands of people or wait many years to see which people go on to develop symptoms.

The current findings provide new information about the cognitive declines associated with normal aging and the extent to which they are accelerated by the major genetic risk factor for Alzheimer’s disease, said Eric Reiman, M.D., Executive Director of the Banner Alzheimer’s Institute, Director of the Arizona Alzheimer’s Consortium, and one of the study authors.

Perhaps more important, these findings add to the evidence that certain Alzheimer’s treatments may be most effective if started not only before people develop symptoms, but even before they reach older ages.

This study highlights the idea that Alzheimer’s disease is a progressive disorder that likely begins well before clinical diagnosis, said Creighton Phelps, Ph.D., who directs the Alzheimer’s Disease Research Center program for the National Institute on Aging. Additional research is needed to identify those at high genetic risk and develop methods to delay disease progression.