Risk for Alzheimer's disease: A review of long-term episodic memory encoding and retrieval fMRI studies

Many risk factors have been identified that predict future progression to Alzheimer's disease (AD). However, clear links have yet to be made between these risk factors and how they affect brain functioning in early stages of AD. We conducted a narrative review and a quantitative analysis to better understand the relationship between nine categories of AD risk (i.e., brain pathology, genetics/family history, vascular health, head trauma, cognitive decline, engagement in daily life, late-life depression, sex/gender, and ethnoracial group) and task-evoked fMRI activity during episodic memory in cognitively-normal older adults. Our narrative review revealed widespread regional alterations of both greater and lower brain activity with AD risk. Nevertheless, our quantitative analysis revealed that a subset of studies converged on two patterns: AD risk was associated with (1) greater brain activity in frontal and parietal regions, but (2) reduced brain activity in hippocampal and occipital regions. The brain regions affected depended on the assessed memory stage (encoding or retrieval). Although the results clearly indicate that AD risks impact brain activity, we caution against using fMRI as a diagnostic tool for AD at the current time because the above consistencies were present among much variability, even among the same risk factor.