The combined influence of beta‐amyloid and vascular risk on prospective brain atrophy in clinically normal individuals
Bibliographic record
Abstract
Abstract Background Amyloid‐beta (Aβ) and vascular risk factors are commonly observed together among cognitively unimpaired adults. Here, we examined the interactive associations of Aβ burden and systemic vascular risk with respect to longitudinal patterns of neurodegeneration. Secondarily, we assessed whether systemic vascular risk associations with brain atrophy were modified after adjusting for imaging based markers of white matter integrity (white matter hyperintensities (WMH) and diffusion‐derived fractional anisotropy). Methods Participants were 197 adults (age=73.5±6.1 years) from the Harvard Aging Brain Study with at least two MRI scans over a median of 4.5 years. Baseline Aβ burden was measured with Pittsburgh Compound‐B PET. Vascular risk was quantified with the Framingham Heart Study general cardiovascular disease risk score. Altered white matter microstructure was measured via diffusion‐derived fractional anisotropy and WMH burden was quantified using FLAIR images. Brain atrophy was assessed longitudinally with serial structural MRI. Aβ burden and vascular risk were examined as interactive and independent predictors of brain atrophy in separate linear mixed models, adjusting for age, sex, education, APOE ε4 status, and intracranial volume (where appropriate). Result We found a significant interaction between elevated Aβ burden and higher vascular risk in relation to faster atrophy within frontal (t=‐2.95, p=0.003) and anterior temporal lobes (t =‐2.32, p=0.021), thalamus (t=‐2.61, p=0.010) and striatum (t =‐2.17, p=0.031). Higher Aβ burden, but not vascular risk, was associated with faster atrophy in the parietal lobes (Aβ: t=‐4.14, p<0.001; vascular risk: t=‐1.54, p=0.124), occipital lobes (Aβ: t=‐2.95, p=0.003; vascular risk: t=‐0.63, p=0.526), and hippocampus (Aβ: t=‐2.72, p=0.007; vascular risk: t=0.207, p=0.836). These effects remained very similar after adjusting for WMH and fractional anisotropy measures. Conclusion Elevated vascular risk was associated with accelerated Aβ‐related atrophy in frontal and anterior temporal regions. However, higher Aβ burden alone was correlated with greater atrophy in regions often associated with a canonical AD pattern of neurodegeneration, including the hippocampus and parietal regions. These findings highlight interactions between vascular and Aβ‐related pathways with respect to brain atrophy, and the potential benefit of managing vascular risk factors as a possible intervention to slow regional neurodegeneration in preclinical Alzheimer’s disease.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".