Early β-amyloid accumulation and hypoconnectivity in the default mode network are related to its disengagement from global brain activity
Bibliographic record
Abstract
A bstract Importance The specific pattern/trajectory of β-amyloid (Aβ) pathology spreading in Alzheimer’s disease (AD), from default mode network (DMN) regions to sensory-motor areas, is well known, but poorly understood. Objective To determine if resting-state global brain activity is linked to early Aβ deposition in the DMN. Design This is a retrospect analysis of multi-modal and longitudinal data from the Alzheimer’s disease Neuroimaging Initiative (ADNI) cohort. Setting The ADNI was a multicenter project involving 63 research centers. Participants The study included 144 participants (72.6 ± 7.5 years; 73 females) of whom 28 were controls, 21 had significant memory concerns, 72 had cognitive impairment ( N =72), and 23 had AD. There were both baseline and 2-year follow-up data for Aβ-PET for 112 of the subjects. They were classified into following stages based on the CSF Aβ42 (CSF+: < 192 ng/L ) and cortical Aβ (PET+: > 0 . 872 SUVR ) levels: non-Aβ-accumulators (CSF-/PET-); early-Aβ-accumulators (CSF+/PET-); and late-Aβ-accumulators (CSF+/PET+). Exposure Resting-state brain activity was assessed by functional magnetic resonance imaging (rsfMRI), whereas glymphatic function was estimated by the coupling between fMRI blood-oxygen-level-dependent (BOLD) signals and CSF movements. Main Outcomes and Measures Cortical Aβ accumulation measured by 18 F-AV45 amyloid-positron emission tomography (PET), CSF Aβ42, and total and phosphorylated tau protein levels in all participants. Results Glymphatic function assessed by fMRI was strongly (ρ > 0.43, P < 0.042) associated with various markers of protein aggregation in early Aβ accumulators in whom Aβ just begins to accumulate cortically in the DMN. Among these early accumulators, the preferential Aβ accumulation in the DMN regions in the subsequent two years was correlated with lower gBOLD signal (ρ = 0.51, P = 0.027) and lower local glymphatic function (ρ = 0.48, P = 0.041) in the same regions at baseline. Conclusions and Relevance Resting-state global brain activity and related glymphatic function are linked to Aβ pathology, particularly its preferential deposition in the DMN at the earliest AD stages. This suggests potential novel early therapeutic directions that might provide disease modification. K ey P oints Question Why does the β-amyloid (Aβ) plaque deposit preferentially in the default mode network (DMN) regions at early preclinical stages of Alzheimer’s disease? Findings In this analytic observational cohort study with 144 subjects, we found that the preferential reduction of global resting-state brain activity in the DMN, as well as its coupling with cerebrospinal fluid movement, was significantly correlated with the preferential Aβ accumulation in these DMN regions among 19 subjects with early Aβ accumulation. Meaning Resting-state global brain activity plays a role in the early Aβ accumulation in the DMN, presumably due to its involvement in glymphatic clearance.
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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) | 0.002 | 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".