Enhanced detection of cortical atrophy in Alzheimer's disease using structural MRI with anatomically constrained longitudinal registration

Cortical atrophy is a defining feature of Alzheimer's disease (AD), often detectable before symptoms arise. In surface‐based analyses, studies have commonly focused on cortical thinning while overlooking the impact of loss in surface area. To capture the impact of both cortical thinning and surface area loss, we used anatomically constrained Multimodal Surface Matching (aMSM), a recently developed tool for mapping change in surface area. We examined cortical atrophy over 2 years in cognitively normal subjects and subjects with diagnoses of stable mild cognitive impairment, mild cognitive impairment that converted to AD, and AD. Magnetic resonance imaging scans were segmented and registered to a common atlas using previously described techniques (FreeSurfer and ciftify), then longitudinally registered with aMSM. Changes in cortical thickness, surface area, and volume were mapped within each diagnostic group, and groups were compared statistically. Changes in thickness and surface area detected atrophy at similar levels of significance, though regions of atrophy somewhat differed. Furthermore, we found that surface area maps offered greater consistency across scanners (3.0 vs. 1.5 T). Comparisons to the FreeSurfer longitudinal pipeline and parcellation‐based (region‐of‐interest) analysis suggest that aMSM may allow more robust detection of atrophy, particularly in earlier disease stages and using smaller sample sizes.