Cortical amyloid burden and age moderate hippocampal activity in cognitively-normal adults

Neurodegeneration in the medial temporal lobe, particularly in the hippocampus, is viewed as the primary source of AD-related memory deficits. Yet, in the earliest preclinical phase of Alzheimer's disease (AD), amyloid-beta (Aβ) plaques deposit primarily in the neocortex, not in the medial temporal lobe. Tau tangles, however, do often aggregate in the medial temporal lobe in parallel with amyloid deposition in the neocortex in AD. In the present study, we focused on the relationship between cortical amyloid deposition and hippocampal activity during a memory-encoding task in a sample of cognitively-normal elderly aged 60-89. We hypothesized that age would moderate the Aβ effect on hippocampal activity, and could explain some of the mixed findings in the literature. We report that high cortical Aβ load was associated with lower task-related hippocampal activity during memory encoding. Importantly, this relationship was found more evident in the younger elderly, even after controlling for subsequent recognition memory of the in-scanner task and a general episodic memory construct score. Furthermore, regional cerebrovascular reactivity measured in a subset of participants showed little role in modifying the age-dependent Aβ effect on hippocampal activity. Our findings support the idea that age is an important variable in understanding hippocampal function in preclinical AD.