Spatially resolved neural slowing predicts impairment and amyloid burden in Alzheimer’s disease
Bibliographic record
Abstract
An extensive electrophysiological literature has proposed a pathological 'slowing' of neuronal activity in patients on the Alzheimer's disease spectrum. Supported by numerous studies reporting increases in low-frequency and decreases in high-frequency neural oscillations, this pattern has been suggested as a stable biomarker with potential clinical utility. However, no spatially resolved metric of such slowing exists, stymieing efforts to understand its relation to proteinopathy and clinical outcomes. Further, the assumption that this slowing is occurring in spatially overlapping populations of neurons has not been empirically validated. In the current study, we collected cross-sectional resting state measures of neuronal activity using magnetoencephalography from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal biomarker-negative older adults. From these data, we compute and validate a new metric of spatially resolved oscillatory deviations from healthy ageing for each patient on the Alzheimer's disease spectrum. Using this Pathological Oscillatory Slowing Index, we show that patients on the Alzheimer's disease spectrum exhibit robust neuronal slowing across a network of temporal, parietal, cerebellar and prefrontal cortices. This slowing effect is shown to be directly relevant to clinical outcomes, as oscillatory slowing in temporal and parietal cortices significantly predicted both general (i.e. Montreal Cognitive Assessment scores) and domain-specific (i.e. attention, language and processing speed) cognitive function. Further, regional amyloid-β accumulation, as measured by quantitative 18F florbetapir PET, robustly predicted the magnitude of this pathological neural slowing effect, and the strength of this relationship between amyloid-β burden and neural slowing also predicted attentional impairments across patients. These findings provide empirical support for a spatially overlapping effect of oscillatory neural slowing in biomarker-confirmed patients on the Alzheimer's disease spectrum, and link this effect to both regional proteinopathy and cognitive outcomes in a spatially resolved manner. The Pathological Oscillatory Slowing Index also represents a novel metric that is of potentially high utility across a number of clinical neuroimaging applications, as oscillatory slowing has also been extensively documented in other patient populations, most notably Parkinson's disease, with divergent spectral and spatial features.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".