Leveraging Autobiographical Memory to Identify Patients at Risk for Alzheimer’s

Research from the University of Arizona (UA) found that people with less detailed memories may be at higher risk for developing Alzheimer’s disease—findings that could mean earlier detection and treatment of a devastating disease with a clinically silent beginning.

The Alzheimer’s Association reports that Alzheimer’s is the sixth leading cause of death in the U.S. and its prevalence is expanding rapidly. Currently, it impacts an estimated 5.7 million Americans, with someone new developing the disease every 65 seconds. Genetic factors account for 60%–80% of the risk of developing Alzheimer’s. One gene variant in particular, APOE ε4, is associated with an increased risk for the disease, with 50%-70% of individuals with Alzheimer’s having at least one ε4 allele.

The challenge is that Alzheimer’s is notoriously difficult to diagnose in the early stages, even though brain changes may begin decades before any memory problems begin. In a press release announcing the new study, lead researcher and University of Arizona neuropsychologist, Matthew Grilli, said: “This raises a huge challenge for developing effective treatments. The hope is that, in the near future, we will have drugs and other treatments that could potentially slow down, stop and even reverse some of these brain changes that we think are the hallmarks of Alzheimer's disease. The problem is that if we can't detect who has these hallmarks early enough, these treatments may not be fully effective, if at all.”

Grilli, an assistant professor and director of the Human Memory Laboratory in the UA Department of Psychology, said the goal of the research was to help identify brain changes much earlier, before they begin to have an obvious effect on cognition and memory. To that end, researchers administered an “autobiographical memory” test to a group of 35 healthy adults who ranged in age from early 50s to 80, half of whom carry APOE ε4. They were asked to recall recent memories, memories from their childhood and memories from early adulthood with as much detail as possible. When responses were evaluated, they revealed that those with the genetic risk factor described memories with much less vivid detail than those without it. This was true despite having all performed normally and comparably on other standard neuropsychology tests.

“They are clinically normal, they are cognitively normal, but there’s this subtle difficulty one group has with retrieving real-world memories, which we think is because there are more people in the group who are at a preclinical stage of Alzheimer's disease,” said Grilli.

Researchers caution that not everyone with the gene variant will develop Alzheimer’s, and not everyone with Alzheimer’s carries the allele. The next phase would be to study brain activity in the group that provided less vivid autobiographical memories to see if there are observable changes in brain structure or activation of the regions of the brain affected early on by Alzheimer’s. Ultimately, researchers hope the findings will lead to new clinical tests capable of identifying the disease at its earliest stages.

“The tests for early signs of Alzheimer’s disease pathology are invasive and expensive, so this new cognitive test potentially could be used as a screen,” Grilli said. “It also could be used to help clinical trials. At the moment, it’s very difficult and expensive to conduct clinical trials of new drugs because it takes a very long time to determine whether that drug has had an impact on memory. If we have more sensitive measures, we might get answers sooner, especially if we're trying to administer drugs before obvious signs of memory impairment are detectable.”

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