Bundle-wise functional connectivity density and fractional amplitude of low-frequency fluctuations decrease in white matter in preclinical Alzheimer's disease and are associated with A[beta] levels and cognition
Bibliographic record
Abstract
Neurophysiological changes associated with Alzheimer’s disease (AD) begin decades before clinical symptoms emerge, during preclinical AD. Functional abnormalities in White Matter (WM) at this preclinical stage remain largely unexplored. We obtained resting-state functional Magnetic Resonance Imaging (rs-fMRI) data of 295 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and evaluated bundle-wise Functional Connectivity Density (FCD) and fractional Amplitude of Low-Frequency Fluctuations (fALFF) across 46 bundles, which reflects the strength of synchronizations of BOLD dynamics between each WM bundle and whole-brain 200 GM parcels, and spontaneous neural activity of each WM bundle, respectively. To mitigate site/scanner effects on the metrics, ComBat harmonization was applied to the data. We then performed permutation tests (n=5,000) on each harmonized metric for each bundle to determine differences in FCD and fALFF in preclinical AD relative to controls, adjusting for sex, age, and education using multiple linear regression. Linear correlations of the metrics with the pathological biomarker beta-amyloid (Aβ) and cognitive scores (mPACC and ADAS11) were assessed using general linear models. Multiple comparisons were corrected via a False Discovery Rate (FDR). We found that preclinical AD patients had reduced FCD and fALFF in specific WM bundles, such as cingulate and hippocampal cingulum, compared to controls (FDR corrected p ⪅ 0.05), some of which were associated with poorer cognitive performance and greater Aβ) accumulation (FDR corrected p < 0.05). This study, to the best of our knowledge, is the first to examine bundle-wise FCD and fALFF of WM in preclinical AD using a large-scale, multisite, cross-sectional dataset, suggesting potential applications of these metrics for assessing preclinical AD with rs-fMRI.
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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 | 0.002 |
| 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".