Neural correlates of episodic memory encoding and resilience to Alzheimer’s Disease in amyloid‐positive cognitively unimpaired individuals

Abstract Background Episodic memory (EM) impairment is an important feature of early Alzheimer’s Disease and is related to well accepted biomarkers of AD. Monitoring healthy individuals for EM impairment may allow for early detection of risk for AD or a better understanding of resilience to cognitive decline. The present study used a functional magnetic resonance imaging (fMRI) EM task to examine whether neural substrates of EM are associated with classic features of AD. Method Healthy adults (n = 120, 84 females, 45‐85 years of age) completed a 5‐minute fMRI EM encoding task which presented photographs of unfamiliar faces and objects with instructions to remember the items for later recognition. Following fMRI preprocessing using FSL, first‐level statistical analysis (using Feat) included an explanatory variable that modeled Items that were correctly remembered in the recognition phase to reflect successful encoding. Group‐level voxel‐wise analysis then examined which of a number of different AD features independently moderated fMRI response during successful encoding, including amyloid deposition from PET, hippocampal volume from MRI, APOE e4 status, and performance on neuropsychological tests (Craft story recall, Multi‐Lingual Naming Test: MINT, global cognition: MOCA). Age, sex and education were included as covariates in all voxel‐wise analyses and activation maps were cluster‐corrected using Z > 3.1, p = .05. Result The only AD marker that significantly moderated EM successful encoding was amyloid status. Amyloid+ individuals (n = 25) recruited an area of the left antero‐lateral temporal cortex (MNI coordinates: x = ‐68, y = ‐30, z = ‐14) more strongly than Amyloid‐ individuals (n = 94). A post‐hoc exploratory analysis (controlling for age, sex and education) revealed that in Amyloid+ individuals, activation in the dorsal aspect of this temporal region was associated with better delayed memory performance (partial r = .426, p = .048) and activation in the ventral aspect of this region was associated with greater left hippocampal volume (partial r = .489, p = .021). In contrast, in Amyloid‐ individuals, activation in the dorsal aspect of this temporal region was associated with better performance on the MINT (partial r = .288, p = .006). Conclusion Recruitment of left lateral temporal cortex during successful encoding in Amyloid+ individuals was associated with better delayed memory recall performance and greater hippocampal volume, suggesting a potential profile of resilience to AD.