Newly published research from UCI MIND scientists shows that people carrying a genetic risk factor (APOE4) for Alzheimer’s disease experience faster and more severe memory loss, but other cognitive abilities remain largely unchanged.
The study, published in Neurology and led by MD/PhD student Casey Vanderlip and Professor Craig Stark in the Department of Neurobiology and Behavior, found that APOE4 specifically affects how and when memory declines in Alzheimer’s disease. While APOE4 is known to increase the likelihood of developing Alzheimer’s disease, this study shows that it also changes the rate of decline, speeding up memory loss while other cognitive abilities were relatively stable in the early stages.
The team analyzed cognitive performance from more than 1500 older adults and used modeling of brain scans to estimate how long each person had amyloid building up in their brains, a key biomarker of Alzheimer’s disease. They then examined how cognitive abilities changed in relation to amyloid duration and genetic status.
Across all participants, memory was the first domain to show change, but people with two copies of APOE4 had the earliest and steepest declines, followed by those with one copy. Individuals with no copies of APOE4 showed the smallest changes. In contrast, non-memory functions followed a similar trajectory regardless of genetic background.
“These findings show that APOE4 does not just increase risk,” said Vanderlip. “It changes the way Alzheimer’s unfolds, targeting memory earlier and more aggressively, while leaving other abilities relatively untouched in the early stages.”
Professor Stark added, “Understanding these APOE4 specific patterns helps us identify who may benefit most from early interventions and what symptoms we should be looking for.”
This work highlights the importance of assessing individual risk factors, like APOE status, when interpreting cognitive changes. Memory loss in aging is not one-size-fits-all and genes like APOE4 may offer important clues about when and how it starts.
This research was supported by the National Institute on Aging.
