Amyloid-β deposition in basal frontotemporal cortex is associated with selective disruption of temporal mnemonic discrimination

Abstract

Cerebral amyloid-beta (A{beta}) accumulation, a hallmark pathology of Alzheimers disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether A{beta} contributes to subtle memory deficits observed during the preclinical stage. The heterogenous emergence of A{beta} deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits. In this context, we tested whether specific domains of mnemonic discrimination, a neural computation essential for episodic memory, exhibit specific deficits related to early A{beta} deposition. We tested 108 cognitively unimpaired human older adults (66% female) who underwent 18F-florbetapir positron emission tomography (A{beta}-PET), and a control group of 35 young adults, on a suite of mnemonic discrimination tasks taxing object, spatial, and temporal domains. We hypothesized that A{beta} pathology would be selectively associated with temporal discrimination performance due to A{beta}s propensity to accumulate in the basal frontotemporal cortex, which supports temporal processing. Consistent with this hypothesis, we found a dissociation in which generalized age-related deficits were found for object and spatial mnemonic discrimination, while A{beta}-PET levels were selectively associated with deficits in temporal mnemonic discrimination. Further, we found that higher A{beta}-PET levels in medial orbitofrontal and inferior temporal cortex, regions supporting temporal processing, were associated with greater temporal mnemonic discrimination deficits, pointing to the selective vulnerability of circuits related to temporal processing early in AD progression. These results suggest that A{beta} accumulation within basal frontotemporal regions may disrupt temporal mnemonic discrimination in preclinical AD, and may serve as a sensitive behavioral biomarker of emerging AD progression.