Serum cholesterol levels and APOEε4 status potentiate metabolic decline in non‐demented individuals
Bibliographic record
Abstract
Abstract Background Epidemiological investigations have shown that midlife elevated total serum cholesterol levels increase the risk of Alzheimer’s disease (AD). However, observational studies in late‐life subjects suggested that high cholesterol levels reduce the risk of dementia. Since hypometabolism is a pivotal marker of AD progression, understanding the impact of peripheral cholesterol levels over the brain’s metabolic state in older adults has become crucial to clarify these seemingly conflicting findings. Therefore, whether high serum cholesterol levels accelerate brain metabolic decline in older subjects remains a key question to be answered. Here, we investigated whether total serum cholesterol levels are associated with cerebral metabolic decline. We hypothesized that elevated total serum cholesterol levels accelerate metabolic decline in AD‐related brain regions. Method We evaluated 499 cognitively unimpaired and mild cognitive impaired elderly subjects (age>55 years) from Alzheimer's Disease Neuroimaging Initiative (ADNI) with available total serum cholesterol measurements at baseline and longitudinal [18F]FDG‐PET scans. Voxel‐wise general linear modelling was used to assess the baseline association between total serum cholesterol levels and cerebral metabolic rate for glucose (CMRglc), as well as cholesterol’s impact over the 2‐year’s rate of metabolic decline. Age, gender, BMI, cholesterol treatment and diagnostic group were set as covariates for adjustment. APOEε4 genotype was used as both, a covariate or an interaction factor. Result No significant associations were observed at baseline. We found a negative correlation between cholesterol levels and the 2‐year CMRglc variation rates in brain regions affected in early stages of AD, which was driven by the interaction with APOEε4 status (Figure 1). Regions affected include the right precuneus (peak t(491) = ‐3.93, p<0.0001) and the right posterior cingulate gyrus (peak t(491) = ‐4.12, p<0.0001). Associations were greater in the right hemisphere. Conclusion Our results support the concept that the interaction of higher serum cholesterol levels with APOEε4 genotype accelerate metabolic decline in AD‐related brain regions. These findings complement cross‐sectional studies postulating that, even among older adults, serum cholesterol levels, in association with the APOEε4 status, might be related to brain functional changes similar to those observed in the development of AD.
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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 | 0.001 |
| 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 | 0.001 | 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".