Results support the feasibility and both the ecological and construct validity of the Virtual Shop.

Hyperactivation, which is defined as a higher level of activation in patients compared to cognitively unimpaired older adults (controls; CTL), might represent an early signature of Alzheimer's Disease (AD). The goal of this study was to assess the presence and location of hyperactivation in individuals with mild cognitive impairment (MCI) who were later diagnosed with dementia, examine how hyperactivation changes longitudinally, and whether it is related to time before dementia. Forty participants, 26 with MCI and 14 CTL were enrolled in the study. Magnetic resonance imaging was used to measure functional activation while participants encoded word-pairs as well as cortical thickness and regional brain volume at study entry (Y0) and two years later (Y2). Clinical follow-up was completed every two years following study entry to identify progressors (pMCI), that is, individuals who later received a diagnosis of dementia. Task-related activation was assessed in pMCI in both hippocampi and in regions showing greater cortical thinning from Y0 to Y2 compared to CTLs. Hyperactivation was found in pMCI individuals in the right supramarginal gyrus. Persons with pMCI also showed hypoactivation in the left hippocampus and left pars opercularis. Both hyper- and hypoactivation were present at Y0 and Y2 and did not change longitudinally. Activation was not associated with time before dementia diagnosis. Smaller volume and thinner cortical thickness were associated with shorter time to diagnosis in the left hippocampus and left pars opercularis. In conclusion, hyperactivation was found in individuals who later progressed to dementia, confirming that it might represent an early biomarker to identify individuals in the prodromal phase of AD and that its understanding could contribute to elucidate the key brain mechanisms that precede dementia.

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.