The relationship of functional hippocampal activity, amyloid deposition, and longitudinal memory decline to memory complaints in cognitively healthy older adults.

We evaluated whether self-reports of worse cognition in older adults with normal cognitive function reflected actual memory decline, amyloid pathology, and subtle vulnerabilities in hippocampal function. We measured subjective cognitive decline (SCD) in 156 older participants from the Dallas Lifespan Brain Study. Functional hippocampal activation during encoding, measured with fMRI, and longitudinal memory change that was measured in the four years preceding the SCD measures were used to predict the magnitude of SCD. A subsample (N=105) also underwent 18F-Florbetapir PET imaging that measured amyloid burden. Results showed that increased SCD were associated with greater prior memory decline and amyloid deposition. Importantly, decreased hippocampal activation during encoding was a significant predictor of SCD, particularly in young-old adults below 69 years old, above and beyond prior memory change and amyloid deposition. These results indicate that multiple measures of neural and cognitive dysfunction are simultaneously associated with SCD. Moreover, SCD in younger seniors appears to reflect deficient hippocampal activity that increases their reports of poorer memory, independent of amyloid. This manuscript is part of the Special Issue entitled "Cognitive Neuroscience of Healthy and Pathological Aging" edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza. This article is part of the Virtual Special Issue titled COGNITIVE NEU-ROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.