A Pilot Study of Changes in Medial Temporal Lobe Fractional Amplitude of Low Frequency Fluctuations after Sildenafil Administration in Patients with Alzheimer’s Disease
Bibliographic record
Abstract
Alzheimer's disease (AD) is the most common cause of neurodegenerative cognitive impairment, defined by abnormal accumulations of amyloid-β and tau. Approaches directly targeting these proteins have not resulted in a disease modifying therapy. Neurovascular unit dysfunction is a feature of AD offering an alternative target for intervention. Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, improves cognitive functioning in mouse models of AD. Recent work in AD patients has demonstrated increased cerebral blood flow, as well as brain oxygen utilization after a single dose of sildenafil. Its effect on nitric oxide-cGMP signaling may have downstream effects on neuroplasticity, amyloid-β processing, and improved neurovascular unit function. Fractional amplitude of low frequency fluctuations (fALFF) assesses spontaneous neural activity via resting state fMRI BOLD signal (0.01-0.08 or 0.10 Hz). In AD, other assessments have revealed increased fALFF in hippocampi and parahippocampal gyri. Here, we examined the effects of a single dose of sildenafil on fALFF in a cohort of 10 AD patients. We found a decrease (p < 0.03, α= 0.05) in fALFF an hour after sildenafil administration in the right hippocampus. Additionally, cerebral vascular reactivity in response to carbon dioxide inhalation, a measure of neural vascular reserve previously collected on most of these participants, was not significantly correlated with this decrease, implying that change in fALFF may not have been solely due to altered vascular reactivity to CO2. We demonstrate that in patients with AD, hippocampal fALFF decreases in response to sildenafil, suggesting a normalization. These findings support further investigation into the effects of sildenafil in 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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.001 | 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".