Increased regional brain inflammation predicts longitudinal brain atrophy in individuals in the Alzheimer’s disease continuum
Bibliographic record
Abstract
Abstract Background Neuroinflammation typically involves the activation of microglial cells in the brain and has been linked to Alzheimer’s disease (AD) pathology. However, how microglial activation influences brain neurodegeneration in individuals across the AD continuum is still poorly understood. Here, we aimed to investigate the influence of microglial activation in longitudinal brain atrophy in individuals across the AD continuum. We hypothesize that high levels of regional brain inflammation predict widespread brain atrophy. Method We assessed 95 individuals from the TRIAD cohort (60 cognitively unimpaired and 35 cognitively impaired) with available [11C]PBR28‐PET, a measure of microglial activation, and a 2‐year longitudinal MRI (mean = 2.07 years). We generated grey matter voxel‐based morphometry (VBM) images using SPM12 and DARTEL, smoothed with a Gaussian kernel of full‐width half maximum of 8mm. We built the uncorrected (p < 0.05) association matrix between the [11C]PBR28‐PET SUVR and longitudinal VBM ROIs (z‐score) with the ß‐estimates from linear regressions accounting for age, sex, and diagnosis. We divided the [11C]PBR28‐PET levels into terciles (low, intermediate, and high) to generate the averages of longitudinal VBM changes. Result Baseline ROI‐based [11C]PBR28‐PET levels associate with longitudinal brain atrophy not only locally but also in distinct brain regions (Fig 1a). After FDR‐correction, the inferior temporal cortex was the region where [11C]PBR28‐PET levels were better associated with widespread longitudinal brain atrophy (Fig. 1b). Brain atrophy was observed in AD‐related regions, including the amygdala, insula, and the superior temporal cortex, independently of global amyloid load and tau (Fig. 1b). Accordingly, individuals with higher [11C]PBR28‐PET levels in the inferior temporal cortex presented increased longitudinal brain atrophy compared to individuals with lower [11C]PBR28‐PET (Fig. 1c). Conclusion We identified increased baseline [11C]PBR28‐PET levels in the inferior temporal cortex that were highly associated with longitudinal brain atrophy in individuals across the AD continuum. Our results demonstrated that higher levels of inflammation in key brain regions could predict widespread longitudinal brain atrophy, suggesting that microglial activation has a detrimental impact on AD‐related neurodegeneration progression.
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".