Damage of the temporal lobe and APOE status determine neural compensation in mild cognitive impairment

233People with aMCI who were APOE4 carriers showed impairment in associative memory compared to controls (dependent variable in the four-path model), which was linked to hippocampal damage (independent variable), as revealed by the significant total effect. On the contrary, memory in aMCI APOE4 noncarriers was less affected by hippocampal volume reduction (no significant total effect) because of recruitment of secondary networks during retrieval through theta (second mediator) and alpha/beta oscillations (third mediator). Moreover, this compensatory activity for hippocampal damage in aMCI APOE4 noncarriers was dependent on temporal lobe integrity as indicated by cortical thickness (first mediator) and the significant four-path indirect effect.