Regional atrophy correlates of domain-specific episodic memory in early Alzheimer’s disease

Sammanfattning: Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) and tau depositions as well as neurodegeneration, and is typically accompanied by a progressive decline in episodic memory. Previous research proposes two neural memory networks that process different stimulus domains. Specifically, a posterior-medial (PM) and an anterior-lateral (AL) network handle scene- and object-specific information, respectively. I aimed to determine if scene- and object-based memory follow different trajectories in early AD stages. Moreover, I tested where on the AD continuum first alterations in measures of regional atrophy occur. Finally, it was assessed if AD proteinopathy and regional atrophy are related to markers of domain-specific episodic memory. In a sample of N = 121 older adults who were cognitively unimpaired (CU) and Aβ negative (CU Aβ-), CU and Aβ positive (CU Aβ+), or had AD-related mild cognitive impairment (MCI Aβ+), regional atrophy measures were obtained using structural magnetic resonance imaging. Aβ and tau burden were quantified using positron emission tomography. Participants completed a mnemonic discrimination task targeting object- and scene-based episodic memory. Analyses of covariance revealed significantly smaller cornu ammonis 2/3 gray matter volumes and a trend towards lower object discrimination in the MCI Aβ+ group compared to both CU groups. In the whole sample, regression models showed that early tau burden was negatively related to object discrimination. Earliest AD-related memory decline might initially affect object-processing memory networks and is possibly driven by tau. Neurodegeneration might not mediate the relationship of AD proteinopathy and cognition until later AD stages.