Deformation‐based morphometry analysis shows early degeneration in Nucleus basalis of Meynert in Subjective Cognitive Decline

Abstract

AbstractBackgroundPeople with subjective cognitive decline (SCD+) are thought to be at greater risk of Alzheimer’s disease (AD). The Nucleus basalis of Meynert (NbM) has been shown to change early in AD (Fernández‐Cabello et al., 2020), and it is the main source of cholinergic projection to entorhinal cortex (EC) (Mesulam et al., 2013). We thus investigated if there was evidence of degeneration in the NbM, or EC in SCD+ participants compared to those without (SCD‐), and if there was a relationship between changes in these regions and SCD status using deformation‐based morphometry (DBM).MethodData included baseline visit MRI scans of 232 cognitively healthy older adults (148 SCD‐; 84 SCD+) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset (using only ADNI2). SCD status was extracted based on the cognitive change index (CCI) of the subjects reported in ADNIMERGE data (CCI ≥16). MRI 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 estimated, and sex‐ and age‐corrected z‐scores were calculated. Two‐sample t‐tests were then used to compare the SCD+:SCD‐ differences.ResultFigure 1 shows the mean z‐score values for NbM and EC regions for both SCD+ and SCD‐ groups. Results for left NbM showed a significant difference between two groups (p = .007), but not for the right NbM (p = .12). However, z‐scored EC volumes did not show any statistically significant difference between groups for either left (p = .58) or right region (p = .41).ConclusionOur results suggest that in SCD+ subjects, while the EC is still intact, neurodegeneration in the NbM appears to have already begun. Quantifying degeneration in the NbM may allow for early diagnosis of AD. Further research is needed to evaluate if such differences can be computed on an individual subject basis for use as a biomarker.