APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer's Disease (AD) and older adults with the apolipoprotein E e4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. In the current study we report the baseline episodic memory task fMRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) study in Montreal, Canada, in which 327 healthy older adults, within 15 years of the parent's conversion to AD, were scanned. During the task fMRI protocol volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to successful spatial source recollection and failures in spatial source recollection, with memory for only item (object) memory. Multivariate task-related partial least squares (task PLS) was used to test the hypothesis that +APOE4 adults with a family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also tested for group differences in the correlation between event-related brain activity and memory performance in +APOE4 compared to -APOE4 adults using behavioral-PLS (B-PLS). We found group similarities in memory performance and in task-related brain activity in the recollection network. However, the B-PLS results indicated there were group differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with parental history of AD. Future research should further investigate the potential to distinguish risk of AD development based on memory performance and associated patterns of brain activity.