Multimodal morphometry reveals hippocampal atrophy and temporoparietal thinning in mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) represents a prodromal stage of Alzheimer’s disease (AD), characterized by early episodic memory impairment and progressive neurodegeneration, most prominently affecting medial temporal lobe structures. Although structural brain alterations are well documented in aMCI, the relative sensitivity of volumetric versus surface-based measures and their relationship to domain-specific cognitive performance remain incompletely understood. We investigated structural brain differences in a cross-sectional sample of 90 participants, including aMCI patients and age-matched healthy older (HO) adults. High-resolution T1-weighted MRI scans acquired at 3T were analyzed using complementary voxel-based morphometry (VBM) and surface-based morphometry (SBM). Group differences in gray matter volume and cortical thickness were assessed while controlling for age, sex, and total intracranial volume where appropriate. Associations between hippocampal gray matter volume and cognitive performance were examined across an extensive neuropsychological battery. Compared with HO controls, aMCI patients exhibited significant gray matter volume reductions in the bilateral hippocampus, left amygdala, right middle cingulate cortex, left nucleus accumbens, and the medial orbital part of the left superior frontal gyrus. Surface-based analyses revealed additional cortical thinning in temporal, temporoparietal, and frontal association regions, including the supramarginal gyrus. Left hippocampal gray matter volume was associated with episodic memory performance and processing speed, indicating that medial temporal atrophy is already behaviorally relevant at the aMCI stage. These findings demonstrate that aMCI is characterized by converging medial temporal and frontolimbic volume loss together with temporoparietal cortical thinning, which are differentially captured by volumetric and surface-based morphometric approaches. Importantly, hippocampal volume loss was directly linked to cognitive performance, underscoring the functional relevance of early structural degeneration. Multimodal morphometric profiling may therefore provide a sensitive framework for characterizing early neurodegenerative changes along the AD continuum.