Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly

Abstract The accumulation of amyloid-beta (Aβ) peptides, a pathologic hallmark of Alzheimer's disease, has been associated with functional alterations in cognitively normal elderly, most often in the context of episodic memory with a particular emphasis on the medial temporal lobes. The topography of Aβ deposition, however, highly overlaps with frontoparietal control (FPC) regions implicated in cognitive control/working memory. To examine Aβ-related functional alternations in the FPC regions during a working memory task, we imaged 42 young and 57 cognitively normal elderly using functional magnetic resonance imaging during a letter Sternberg task with varying load. Based on 18 F-florbetaben-positron emission tomography scan, we determined older subjects' amyloid positivity (Aβ+) status. Within brain regions commonly recruited by all subject groups during the delay period, age and Aβ deposition were independently associated with load-dependent frontoparietal hyperactivation, whereas additional compensatory Aβ-related hyperactivity was found beyond the FPC regions. The present results suggest that Aβ-related hyperactivation is not specific to the episodic memory system but occurs in the PFC regions as well.