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

TL;DR

This study used voxel-based morphometry on MRI scans to identify hippocampal atrophy patterns across Alzheimer's disease stages, highlighting medial temporal degeneration as a key feature and evaluating hippocampal volume as a predictive biomarker.

Contribution

It provides detailed voxel-based analysis of hippocampal atrophy across AD spectrum and assesses genetic influences and predictive value of hippocampal volume.

Findings

Significant hippocampal atrophy in AD compared to controls and MCI

Hippocampal volume predicts MCI to AD conversion with AUC=0.66

No significant APOE4 effect on hippocampal volume

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.