Nucleus basalis of Meynert degeneration starts in the earliest stages of Alzheimer’s disease: A deformation‐based morphometry analysis
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".