Association between basal forebrain volume and age in the presenilin‐1 E280A autosomal dominant Alzheimer's disease kindred
Bibliographic record
Abstract
INTRODUCTION: The basal forebrain (BF), a key cholinergic hub, undergoes atrophy in Alzheimer's disease (AD), contributing to cognitive decline. However, its age-related differences and early vulnerability in autosomal dominant AD (ADAD) remain unclear. METHODS: We studied 158 individuals from the Colombian Presenilin-1 (PSEN1) E280A kindred, including 80 carriers (60 cognitively unimpaired, 20 cognitively impaired). Participants underwent structural magnetic resonance imaging, blood sampling, and neuropsychological testing. Analysis of covariance and false discovery rate-corrected t tests assessed group differences. Correlations evaluated associations among BF volume, age, and cognitive scores. Hamiltonian Markov chain Monte Carlo modeling estimated the age at which BF volume diverged between carriers and non-carriers. RESULTS: BF volume was comparable between cognitively unimpaired carriers and non-carriers but declined more rapidly in carriers, with divergence at ≈ 37.8 years, 6 years prior to the median age at onset of mild cognitive impairment. DISCUSSION: BF volume changes precede the onset of clinical symptoms in ADAD, supporting its potential as an early biomarker of cholinergic degeneration and therapeutic target. HIGHLIGHTS: There were not basal forebrain (BF) volume differences between PSEN1 E280A unimpaired carriers and non-carriers. Age-related modeling revealed a faster BF volume decline in carriers vs non-carriers. Age-related differences first emerged at 37.8 years, about 6 years before clinical onset. BF volume was related to age, cognition, and plasma phosphorylated tau 217 levels. BF changes may be early indicators of Alzheimer's disease-related neurodegeneration.
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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 | 0.001 | 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) | 0.001 | 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".