Adults having a close relative with Alzheimer’s disease do more poorly in online paired-learning tasks than adults without such a family history, new research has found. Additionally, this impairment appears to be worsened by having diabetes or a genetic variation in the apolipoprotein E (APOE) gene linked to the disease.

The findings may help identify people who have increased risk for developing Alzheimer’s disease and could uncover new ways to delay or prevent the disease.

“Identifying factors that reduce or eliminate the effect of a family history of Alzheimer’s disease is particularly crucial since there is currently no cure or effective disease-slowing treatments,"

lead author Joshua Talboom, PhD, a Postdoctoral Fellow at the Translational Genomics Research Institute, said.

Well-known Risk Factor

Having a family history of Alzheimer’s disease is a well-known risk factor for developing the condition, but the effects on learning and memory throughout a person’s life are less clear. Some studies have been conducted in this area, but most have been too small to draw significant conclusions.

To enable a larger study, Talboom and colleagues created an easy-to-use website,, that participants could log on to and complete a memory test. Participants were asked to learn 12-word pairs and were then tested on their ability to complete the missing half of the pair when presented with one of the words.

[caption id=“attachment_99149” align=“aligncenter” width=“680”]Apolipoprotein E (APOE) ε4 alleles negatively influence PAL performance in the presence of FH Apolipoprotein E (APOE) ε4 alleles negatively influence PAL performance in the presence of FH
Credit: Joshua S Talboom et al CC-BY[/caption]

The 59,571 individuals who participated were also asked to answer questions about their sex, education, age, language, country and health, including a question about whether one of their parents or siblings had been diagnosed with Alzheimer’s disease. Those with a family history of Alzheimer’s were able to match about two and one-half fewer word pairs than individuals without a family history. Having diabetes appeared to compound the learning impairments seen in individuals with a family history.

Apolipoprotein ε4 Allele

A subset of 742 participants who had a close relative with Alzheimer’s submitted a sample of dried blood or saliva that the researchers tested for a genetic variation in the APOE gene linked to the disease.

“The APOE genotype is an important genetic factor that influences memory, and we found that those with the variation performed worse on the memory test than those without the variation,"

Talboom explains.

Some characteristics, however, appeared to protect against learning and memory impairments in people with a family history of Alzheimer’s disease.

Participants with higher levels of education experience less of a decline in scores on the learning and memory test than people with lower levels of education, even when they have a family history of the disease. Women also appear to fair better despite having Alzheimer’s disease risk factors.

“Our study supports the importance of living a healthy lifestyle, properly treating diseases such as diabetes, and building learning and memory reserve through education to reduce the cognitive decline associated with Alzheimer’s disease risk factors,"

concludes senior author Matthew Huentelman, Professor of Neurogenomics at the Translational Genomics Research Institute, Arizona. Support for the work came from the Mueller Family Charitable Trust, Arizona Department of Health Services, Flinn Foundation, and National Institutes of Health.

Joshua S Talboom, Asta Håberg, Matthew D De Both, Marcus A Naymik, Isabelle Schrauwen, Candace R Lewis, Stacy F Bertinelli, Callie Hammersland, Mason A Fritz, Amanda J Myers, Meredith Hay, Carol A Barnes, Elizabeth Glisky, Lee Ryan, Matthew J Huentelman Family history of Alzheimer’s disease alters cognition and is modified by medical and genetic factors eLife 2019;8:e46179 DOI: 10.7554/eLife.46179

Top Image: Maxime Lebrun/Unsplash

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