INTRODUCTION: Visual short-term memory (VSTM) is a critical indicator of Alzheimer's disease (AD), but whether its neural substrates could adapt to early disease progression and contribute to cognitive resilience in amnestic mild cognitive impairment (aMCI) has been unclear. METHODS: Fifty-five aMCI patients and 68 normal controls (NC) performed a change-detection task and underwent multimodal neuroimaging scanning. RESULTS: Among the atrophic brain regions in aMCI, VSTM performance correlated with the volume of the right prefrontal cortex (PFC) but not the medial temporal lobe (MTL), and this correlation was mainly present in patients with greater MTL atrophy. Furthermore, VSTM was primarily correlated with frontal structural connectivity in aMCI but was correlated with more distributed frontal and MTL connectivity in NC. DISCUSSION: This study provided evidence on neural adaptation in the precursor stages of AD, highlighting the compensatory role of PFC as MTL deteriorated and suggesting potential targets in early intervention for cognitive preservation. HIGHLIGHTS: Atrophic left medial temporal lobe (MTL) no longer correlated with visual short-term memory (VSTM) in amnestic mild cognitive impairment (aMCI). Atrophic right middle frontal area continued to correlate with VSTM in aMCI. Frontal brain-behavior correlation was mainly present in the aMCI subgroup with greater medial temporal lobe (MTL) atrophy. Reliance of VSTM on frontal connectivity increased in compensation for MTL dysfunction.