The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition
Bibliographic record
Abstract
ABSTRACT INTRODUCTION Cognitive decline in Alzheimer’s disease is associated with amyloid-β accumulation, neurodegeneration and cerebral small vessel disease, but the temporal relationships between these factors is not well established. METHODS Data included white matter hyperintensity (WMH) load, grey matter (GM) atrophy and Alzheimer’s Disease Assessment Scale-Cognitive-Plus (ADAS13) scores for 720 participants and cerebrospinal fluid amyloid (Aβ1-42) for 461 participants from the Alzheimer’s Disease Neuroimaging Initiative. Linear regressions were used to assess the relationships between baseline WMH, GM, and Aβ1-42 to changes in WMH, GM, Aβ1-42, and cognition at one-year follow-up. RESULTS Baseline WMHs and Aβ1-42 predicted WMH increase and GM atrophy. Baseline WMHs, GM, and Aβ1-42 predicted worsening cognition. Only baseline Aβ1-42 predicted change in Aβ1-42. DISCUSSION Baseline WMHs lead to greater future GM atrophy and cognitive decline, suggesting that WM damage precedes neurodegeneration and cognitive decline. Baseline Aβ1-42 predicted WMH increase, suggesting a potential role of amyloid in WM damage. Research in Context Systematic Review : Both amyloid β and neurodegeneration are primary pathologies in Alzheimer’s disease. White matter hyperintensities (indicative of presence of cerebrovascular disease) might also be part of the pathological changes in Alzheimer’s. However, the temporal relationship between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline is still unclear. Interpretation : Our results establish a potential temporal order between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline, showing that white matter hyperintensities precede neurodegeneration and cognitive decline. The results provide some evidence that amyloid β deposition, in turn, precedes accumulation of white matter hyperintensities. Future Directions : The current findings reinforce the need for future longitudinal investigations of the mechanisms through which white matter hyperintensities impact the aging population in general and Alzheimer’s disease patients, in particular.
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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 | 0.008 | 0.044 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.005 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".