| Summary: | The goal of this study was to assess how task-related hyperactivation relates to brain network dysfunction and memory performance in individuals at risk of Alzheimer’s disease (AD). Eighty participants from the CIMA-Q cohort were included, of which 28 had subjective cognitive decline plus (SCD+), as they had memory complaints and worries in addition to a smaller hippocampal volume and/or an APOE4 allele, 26 had amnestic mild cognitive impairment (MCI) and 26 were healthy controls without memory complaints. Functional magnetic resonance imaging (fMRI) activation was measured during an object-location memory task. Seed-partial least square analyses (seed-PLS) were conducted in controls and in the SCD+/MCI groups to yield sets of orthogonal latent variables (LVs) assessing the triple association between: i) seed activity in brain regions found to be hyperactive in individuals at risk of AD (left hippocampus, left superior parietal lobule, right inferior temporal lobe), ii) latent patterns of whole-brain task-related activation, and iii) associative memory performance. Three LVs in the SCD+ and MCI groups (67.88% of total covariance explained) and two LVs in the controls (77.85% of total covariance explained) were significant. While controls and SCD+/MCI groups shared a common pattern of memory-related connectivity, patterns of hyperactivation-networks interactions were unique to the clinical groups. Interestingly, higher hippocampal connectivity was associated with poorer memory performance whereas higher neocortical connectivity predicted better memory performance in SCD+ and MCI groups. Our data provides empirical evidence that early dysfunction in brain activation and connectivity is present in the very early stages of AD and offers new insights on the relationship between functional brain alterations and memory performance.
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