The ups and downs of the posteromedial cortex: age- and amyloid-related functional alterations of the encoding/retrieval flip in cognitively normal older adults.

Neural networks supporting memory function decline with increasing age. Accumulation of amyloid-β, a histopathological finding in Alzheimer's disease, is a likely contributor. Posteromedial cortices (PMCs) are particularly vulnerable to early amyloid pathology and play a role in both encoding and retrieval processes. The extent to which aging and amyloid influence the ability to modulate activity between these processes within the PMC was investigated by combining positron emission tomography-amyloid imaging with functional magnetic resonance imaging in cognitively normal older and young adults. Young subjects exhibited a marked decrease in activity during encoding and an increase during retrieval (also known as encoding/retrieval "flip"). Impaired ability to modulate activity was associated with increasing age, greater amyloid burden, and worse memory performance. In contrast, the hippocampus showed increased activity during both encoding and retrieval, which was not related to these variables. These findings support a specific link between amyloid pathology and neural dysfunction in PMC and elucidate the underpinnings of age-related memory dysfunction.