APOE and Mental deterioration: Critically, TPOsup atrophy mediated 30.43% of the negative effect of <i>APOE ε4</i> on global cognition, as measured by the Mini-Mental State Examination (MMSE), and was significantly associated with impaired orientation.<h4>Conclusion</h4>The TPOsup may represent a key neural hub linking <i>APOE ε4</i> to cognitive decline in MCI and may serve as a specific imaging marker for risk stratification in this population.