The impact of individual vascular risk factors on longitudinal neurodegeneration in cognitively unimpaired individuals
Bibliographic record
Abstract
Abstract Background Vascular risk factors (VRFs) have an important role in the etiology and progression of Alzheimer´s Disease (AD). We recently described that VRF burden interacts with AD pathophysiology increasing plasma neurofilament light (NfL) levels, a biomarker of neuroaxonal damage. However, whether individual VRFs interact with AD pathophysiology to promote longitudinal neurodegeneration remains to be elucidated. Here, we aimed to assess the impact of individual VRFs in the longitudinal trajectory of plasma NfL in cognitively unimpaired (CU) individuals. Method We assessed 269 CU individuals from the ADNI cohort with available baseline medical data and cerebrospinal fluid (CSF) Elecsys biomarkers (Aβ1‐42 and p‐tau181), as well as longitudinal measures of plasma NfL. Individuals with both Aβ1‐42 and p‐tau181 positivity were defined as having preclinical AD (A+T+). The VRFs assessed in our analysis were history of cardiovascular disease (CAD), hypertension (HTN), diabetes mellitus (DM), hyperlipidemia (HLP), stroke or transient ischemic attack, smoking, atrial fibrillation, and left ventricular hypertrophy. Only those VRFs with at least 5% prevalence in the studied population were included in our analysis. Result The following VRFs were included in the final analysis based on prevalence: HTN, CAD, DM, and HLP. Linear mixed‐effects (LME) models revealed that no individual VRF significantly interacted with AD pathophysiology to increase longitudinal values of plasma NfL (HTN X AD pathophysiology X time, β =0.97 p=0.63; CAD X AD pathophysiology X time, β = 2.68, p= 0.36; HLP X AD pathophysiology X time, β= ‐2.1, p=0.3). DM was not present among individuals positive for AD pathophysiology. On the other hand, VRF burden significatively interacted with AD to increase NfL levels (VRF burden x AD pathology x time; β = 5.08, P = 0.016). Conclusion We observed that no individual VRF interacted with AD pathophysiology to promote longitudinal neurodegeneration in CU individuals. Our findings suggest that the cumulative number of VRFs, rather than any VRF individually, impacts on neurodegeneration in the context 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 | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 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".