A quadratic function of activation in individuals at risk of Alzheimer's disease

Abstract Introduction Brain activation is hypothesized to form an inverse U‐shape in prodromal Alzheimer's disease (AD), with hyperactivation in the early phase, followed by hypoactivation. Methods Using task‐related functional magnetic resonance imaging (fMRI), we tested the inverse U‐shape hypothesis with polynomial regressions and between‐group comparisons in individuals with subjective cognitive decline plus (SCD+; smaller hippocampal volumes compared to a group of healthy controls without SCD and/or apolipoprotein E [APOE] ε4 allele) or mild cognitive impairment (MCI). Results A quadratic function modeled the relationship between proxies of disease severity (neurodegeneration, memory performance) and left superior parietal activation. Linear negative functions modeled the relationship between neurodegeneration and left hippocampal/right inferior temporal activation. Group comparison indicated presence of hyperactivation in SCD+ and hypoactivation in MCI in the left superior parietal lobule, relative to healthy controls. Discussion These findings support the presence of an inverse U‐shape model of activation and suggest that hyperactivation might represent a biomarker of the early AD stages.

Abstract licence: CC BY-NC

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