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

Alzheimers Dement (Amst). 2021 Jan 20;12(1):e12139. doi: 10.1002/dad2.12139. eCollection 2020.


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.

Keywords: Alzheimer's disease; associative memory; functional magnetic resonance imaging; hyperactivation; mild cognitive impairment; subjective cognitive decline.