Longitudinal Surface-Based Morphometry Changes in the Hippocampus in Dementia

The hippocampus is central to Alzheimer’s disease (AD), characterized by atrophy and cognitive decline. While volume loss is well-documented, surface-based morphometric (SBM) features—curvature, gyrification, and thickness—remain less explored. Using T1-weighted MRI data from the Alzheimer’s Disease Neuroimaging Initiative (4,617 timepoints; CN: 475, MCI: 673, AD: 269), hippocampal subfields were analyzed with HippUnfold. Linear mixed effects models examined volume and SBM changes, tracking cognitive trajectories in stable (n = 1017) and progressing (n = 301) individuals.

Focusing on CA1, the stable AD group showed significant volume reductions (β = −1.01, p < .001) compared to CN (β = 6.19, p < .001). SBM metrics significantly increased over time across subregions (e.g., curvature: CN: β = −0.72, p < .001; AD: β = 0.006, p < .001), though gyrification did not reach significance in bilateral CA1, CA3, CA4, and subiculum. Time-dependent interactions indicated progressive volume loss and SBM increases across groups (all p’s < .001). Notably, SBM metrics predicted cognitive improvements in AD.

While volume loss remains a key AD marker, it may not capture early morphometric changes. SBM features provide additional insights, underscoring the need for integrated volumetric and surface-based analyses to refine disease detection and therapeutic strategies.