Detecting short-interval longitudinal cortical atrophy in neurodegenerative dementias via cluster scanning: A proof of concept

Regional brain atrophy estimated from structural magnetic resonance imaging (MRI) is a widely used measure of neurodegeneration in Alzheimer’s disease (AD), Frontotemporal Lobar Degeneration (FTLD), and other dementias. Yet, traditional MRI-derived morphometric estimates are susceptible to measurement errors, posing a challenge for reliably detecting longitudinal atrophy, particularly over short intervals. Here, we examined the utility of multiple MRI scans acquired in rapid succession (i.e., cluster scanning ) for detecting longitudinal cortical atrophy over 3- and 6-month intervals within individual patients. Four individuals with mild cognitive impairment or mild dementia likely due to AD or FTLD participated in this study. At baseline, 3 months, and 6 months, structural MRI data were collected on a 3 Tesla scanner using a fast 1.2-mm T1-weighted multi-echo magnetization-prepared rapid gradient echo (MEMPRAGE) sequence (acquisition time = 2’23’’). At each timepoint, participants underwent up to 32 MEMPRAGE scans acquired in four separate sessions over two days. Using linear mixed-effects models, phenotypically vulnerable cortical (“core atrophy”) regions exhibited statistically significant longitudinal atrophy in all participants (i.e., decreased cortical thickness) by 3 months and further demonstrated preferential vulnerability compared to control regions in three of the participants over at least one of the 3-month intervals. These findings provide proof-of-concept evidence that pooling multiple morphometric estimates derived from cluster scanning can detect longitudinal cortical atrophy over short intervals in individual patients with neurodegenerative dementias.