Precise Alterations in Hippocampal Neural Deterioration and Neural Correlates of Visual Short-Term Memory in Individuals with Amnestic Mild Cognitive Impairment

Abstract

PurposeAtrophy of the hippocampus is an early biomarker of Alzheimers disease (AD) and a main contributor to the patients mnemonic degeneration. While previous research has mostly focused on how hippocampal atrophy impaired long-term memory performance, its relation to short-term memory impairment, which was also found among patients with AD, remains largely uninvestigated. Filling this gap, the current study examined how atrophy in the hippocampus and its subfields may have influenced visual short-term memory (VSTM) in patients with amnestic mild cognitive impairment (aMCI), a common precursor of AD. MethodsFifty-eight aMCI patients and 69 healthy controls (HC) matched in age were included in the current study. VSTM was assessed using an adapted change detection task with a memory load of 2 or 4 items. Hippocampal subfields were automatically segmented in T1-weighted image using FreeSurfer and were manually inspected for errors. Volumes of the subfields were extracted and compared between aMCI and HC subjects using ANCOVA with age, gender and education as covariates. Furthermore, we also examined the partial correlation between VSTM performances and hippocampal subfield volumes with age, gender and education as covariates. ResultsCompared to HC subjects, aMCI subjects had lower response accuracy (ACC) and lower memory capacity under both load conditions and had longer reaction time (RT) in the 2-load condition. Left hippocampus volume was significantly smaller in aMCI and was positively correlated with ACC and capacity in HC but not in aMCI. Among the hippocampal subfields, left hippocampal tail, left molecular layer, left dentate gyrus (DG), left CA4, bilateral subiculum, bilateral presubiculum, bilateral fimbria, were significantly smaller while right hippocampal fissure was significantly widened in aMCI compared to HC. Volumes of the left subiculum, left molecular layer, left DG and left CA4 were positively correlated with ACC and capacity in HC but not in aMCI. Bilateral fimbria volume was negatively correlated with RT under the 2-load condition in HC but not in aMCI. ConclusionThe results of this study suggested that hippocampal deterioration, especially in subfields related to information input and output (e.g. molecular layer, DG, subiculum), may have contributed to VSTM impairment in aMCI by disrupting hippocampal-cortical communications. This finding adds to increasing evidence of hippocampal engagement in short-term memory processes and points to VSTM impairment as a potential neuropsychological indicator for MCI and AD.