Background: Both apolipoprotein E e4 (APOE4) allele and first-degree amily history (FH) of sporadic Alzheimer's disease (AD) increase the prevalence of neurofibrillary tangles and amyloid plaques in the brain, characteristic athology in AD, and are well-established risk factors for developing AD. The purpose of this study was to determine how these risk factors ifferentially affect fMRI neurocognitive responses over a four year interval in healthy middle-aged adults. Methods: We examined 51 cognitively normal iddle-aged subjects without APOE e4 (APOE4-) and 29 subjects with APOE e4 genotype (APOE4+) over two visits, with an overall mean age of 5 years at baseline and an average interval of approximately 4 years between visits. All participants underwent functional magnetic resonance maging (fMRI) encoding task that involved discriminating novel items from previously learned items during both testing sessions. The difference n fMRI signal to novel items over time was extracted and compared. A two-sample t-test was used to detect group differences, with gender, interval etween two sessions, and presence/absence of first-degree family history of dementia as covariates. Analyses were restricted only to regions activated by he encoding task. Results: A greater change in fMRI signal in response to novel items was detected in the left anterior tip of the hippocampus and left uperior temporal gyrus with the APOE4+ > APOE4- contrast. The reverse contrast (APOE4-> APOE4+) revealed no significant voxels. Similarly, FH ad no significant effect on signal change between the two visits when controlling for gender, interval between two sessions, and presence/absence of POE e4. Conclusions: These findings suggest that there may be an upregulation of left anterior hippocampal activation over time in subjects with POE e4 polymorphism even before development of symptomatic disease and may represent preclinical changes in this cognitively normal but highrisk roup compared to controls.
Sridharan, A., Xu, G., Kastman, E., Oh, J., Ries, M., Hermann, B., … Johnson, S. (2011). P1-353: Longitudinal changes in left anterior hippocampal activation in cognitively normal subjects with APOE ε4 polymorphism. Alzheimer’s & Dementia, 7, S225–S225. https://doi.org/10.1016/j.jalz.2011.05.633