Pathological Continuum From the Rise in Pulse Pressure to Impaired Neurovascular Coupling and Cognitive Decline
Bibliographic record
Abstract
The "biomechanical hypothesis" stipulates that with aging, the cumulative mechanical damages to the cerebral microvasculature, magnified by risk factors for vascular diseases, contribute to a breach in cerebral homeostasis producing neuronal losses. In other words, vascular dysfunction affects brain structure and function, and leads to cognitive failure. This is gathered under the term Vascular Cognitive Impairment and Dementia (VCID). One of the main culprits in the occurrence of cognitive decline could be the inevitable rise in arterial pulse pressure due to the age-dependent stiffening of large conductance arteries like the carotids, which in turn, could accentuate the penetration of the pulse pressure wave deeper into the fragile microvasculature of the brain and damage it. In this review, we will discuss how and why the vascular and brain cells communicate and are interdependent, describe the deleterious impact of a vascular dysfunction on brain function in various neurodegenerative diseases and even of psychiatric disorders, and the potential chronic deleterious effects of the pulsatile blood pressure on the cerebral microcirculation. We will also briefly review data from antihypertensive clinical trial aiming at improving or delaying dementia. Finally, we will debate how the aging process, starting early in life, could determine our sensitivity to risk factors for vascular diseases, including cerebral diseases, and the trajectory to VCID.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".