Deformation‐based morphometry analysis shows early degeneration in Nucleus basalis of Meynert in Alzheimer’s disease

Abstract Background Nucleus basalis of Meynert (NbM) is the main source of cholinergic projection to the cerebral cortex, including entorhinal cortex (EC). Both cholinergic cells of NbM and their receptive targets in EC show degeneration during early stages of Alzheimer’s disease (AD). While precise delineation of NbM region on T1w scans is difficult due to limited spatial resolution and contrast, we sought to quantify the degeneration of NbM along the disease trajectory and confirm recent studies suggesting that NbM degeneration happens before degeneration in the EC using deformation‐based morphometry (DBM). Method Data included MRI scans of 1473 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Resolution was increased to 0.5 mm isotropic voxel‐size before non‐linear registration to an ADNI‐based unbiased symmetric template. The resulting deformation fields were used to compute the Jacobian determinant map for each subject as a proxy for local volume. NbM and EC masks were mapped to our high‐resolution template and mean determinant values inside these masks were calculated for groups with different baseline diagnosis, and sex‐ and age‐corrected z‐scores were calculated. Two‐sample t‐tests were then used to compare the scores between different groups. Result Figure 1 shows the mean DBM score of both NbM and EC regions for Normal Controls (CN), subjects with early‐ and late‐stage mild cognitive impairment (EMCI and LMCI) and subjects with probable AD dementia. Results corrected for multiple comparisons showed a significant difference between CN and both EMCI and LMCI for left and right NbM. A significant difference was also observed between EMCI and LMCI in left NbM (p‐value = 0.0024). Z‐scored EC volumes did not show a significant difference between CN and EMCI groups; However, results from EMCI and LMCI differ significantly in both hemispheres. We also observed the expected differences between each group with AD in both NbM and EC (P<0.001). Conclusion Our results show that while macroscopic changes in EC emerge as MCI subjects advance toward the later stages, NbM degeneration starts sooner, as early as preliminary stages of MCI. This points to MRI‐based measurements of NbM as potential biomarkers for early detection of AD and as a marker of disease burden.