The Impact of Early Life Bilateral Salpingo‐Oophorectomy on the Nucleus Basalis of Meynert
Bibliographic record
Abstract
Abstract Background Alzheimer's disease (AD) disproportionately affects women. Women with early‐life bilateral salpingo‐oophorectomy (BSO) have a yet higher risk of late‐life AD. The cholinergic pathway in the basal forebrain, comprising cholinergic nuclei 1, 2, and 3 (Ch123) and the nucleus basalis of Meynert (NBM, i.e., Ch4), are sensitive to estradiol and its atrophy is a marker for AD risk. We wondered whether BSO‐mediated estradiol depletion would affect its structure thereby helping to elucidate these women's trajectory toward late‐life AD risk. Methods Participants included women with early BSO taking estradiol therapy (BSO ET ; n = 24, M±SD age at scan = 45.1±5.2), women with early BSO without ET (BSO; n = 27, M±SD age = 47.3±6.5) and age‐matched controls (AMC; n = 22, M±SD age = 44.0±5.5) from Toronto and Montreal, Canada. T1‐weighted MRI scans (Siemens Prisma/Philips 3T) were preprocessed using the Computational Anatomy toolbox (CAT12). Cholinergic volumes (Ch123, NbM) were identified using cytoarchitectonic probabilistic maps from the JuBrain Anatomy toolbox. Group comparisons were assessed using bivariate analysis (ANOVA, or X 2 ). Partial least squares correlation (PLSC) was then used to examine associations only in the women with BSO between basal forebrain volumes and BSO‐related variables (e.g., time since BSO, estradiol therapy) and hormone levels (estradiol, progesterone). Statistical strength of the model was assessed using resampling methods (permutation test and bootstrap). Results Groups did not differ significantly in age or education. Women with BSO ET had higher estradiol levels at scan (M±SD = 38.5±36.5) than AMC (36.2±28.1) and BSO (17.6±8.1). They also had higher progesterone levels at scan (BSO ET : M±SD = 8.0±17.0) than both groups (AMC: 3.3±5.8; BSO: 1.9±3.8). Bivariate analysis did not find significant differences in Cholinergic volumes among the three groups. However, exploratory PLSC of BSO groups identified one latent variable explaining 95.2% of the covariance ( p = 0.006) which linked older age at scan and more time since BSO (irrespective of estradiol therapy) to smaller NbM volumes bilaterally. Conclusion Preliminary findings suggest that aging and early‐BSO may influence basal forebrain structure. Future work should disentangle age/time‐since‐BSO from estradiol loss. It might also investigate further memory circuit disruption by examining surrounding cholinergic white matter pathways further identifying early AD biomarkers.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".