Hippocampal Atrophy Patterns Across the Alzheimer's Disease Spectrum: A Voxel-Based Morphometry Analysis

Abstract: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are associated with progressive gray matter loss, particularly in medial temporal structures. In this study, CAT12/SPM12 voxel-based morphometry was applied to baseline T1-weighted MRI scans from 249 ADNI participants (CN = 90, MCI = 129, AD = 30). Gray matter volume was analyzed using a general linear model, with the diagnostic group as primary predictor and age and total intracranial volume as covariates. Statistical maps were thresholded at p < 0.001 (voxelwise) and corrected for multiple comparisons at the cluster level using family-wise error (FWE) correction (p < 0.05). Significant hippocampal atrophy was observed in AD relative to CN and MCI (Cohen's d = 2.03 and 1.61, respectively). Hippocampal volume demonstrated moderate predictive value for conversion from MCI to AD (AUC = 0.66). Stratification by APOE4 status did not reveal significant genetic effects on cross-sectional hippocampal volume. These results support medial temporal degeneration as a key feature of AD progression and provide insights into predictive biomarkers and genetic influences.