Nucleus basalis of Meynert degeneration starts in the earliest stages of Alzheimer’s disease: A deformation‐based morphometry analysis
Neda Shafiee, Mahsa Dadar, R. Nathan Spreng, D Louis Collins- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
One of the earliest pathological events in the course of AD is thought to be the degeneration of cholinergic neurons in the basal forebrain (Grothe et al. 2012). The largest cluster of cholinergic cells within the basal forebrain are found in the Nucleus basalis of Meynert (NbM) (Hampel et al. 2020). Studies show that loss of cholinergic projections due to cholinergic degeneration in NbM, is associated with the decline in cognitive abilities, specifically in memory and attention processing (Mesulam et al. 2013). However, identifying the NbM region on MR images is difficult due to limitations in the resolution and contrast of T1w images.
Method
Data included the baseline MRI scans of 677 amyloid‐positive subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset from ADNI1, 2, and GO. Scan resolution was increased to 0.5 mm isotropic voxel size by super‐sampling (Manjón et al. 2010) before non‐linear registration to an ADNI‐based unbiased template. The resulting deformation fields were used to compute the Jacobian determinant map for each subject as a proxy for local volume. A voxel‐wise linear regression model analysis was performed on Jacobian maps to assess the pattern of volumetric change within an NbM mask according to diagnosis: DBM ∼ 1+Dx+AGE+Dx:AGE+SEX; where DBM are the Jacobian values for subjects, Dx is the categorical variable for disease stage (NC, eMCI, lMCI, AD) and Dx:AGE is an interaction term between diagnosis and age of each subject.
Result
Figure 1 shows the statistically significant differences in local volume, comparing successive disease stages, within the NbM mask, after FDR correction (coronal section, A) NC vs eMCI, B) eMCI vs lMCI, C) lMCI vs AD). As it has been shown here, the Jacobian map (as a proxy for atrophy) becomes more pronounced as the disease advances.
Conclusion
Our results show that NbM degeneration starts as early as the preliminary stages of mild cognitive impairment, and this change accelerates as the disease progresses. This points to MRI‐based measurements of NbM as potential biomarkers for early AD detection and as a marker of disease burden.