Bibliographic record
Abstract
Agitation is challenging to treat in Alzheimer’s disease (AD) and has significant implications for patients and caregivers. A major source of difficulty in identifying safe and effective treatments for agitation is the lack of validated biomarkers. The goal of this work was to investigate biomarkers of agitation in patients with AD. Study 1: This study systematically reviewed 57 papers investigating biomarkers of agitation in AD. Studies 2-5: Blood samples were collected from 38 participants enrolled in a randomized, placebo-controlled trial investigating nabilone, a synthetic cannabinoid, for the treatment of agitation in AD. The cross-sectional and longitudinal associations between agitation and 24-S-hydroxycholesterol (cerebrocholesterol (Cchol) (study 2), lipid peroxidation markers of oxidative stress (OS) (study 3), and inflammatory cytokines (study 4) and a biosignature of response to nabilone (study 5) were investigated. These processes are altered in AD and may be associated with agitation and/or endocannabinoid signalling. Study 1: Of six classes of biomarkers identified, most were diagnostic in nature, substantiating the need for studies investigating the longitudinal associations between biomarkers and agitation in AD. Study 2: Cchol was associated with agitation severity cross-sectionally, and longitudinally. However, Cchol did not predict response to nabilone, and did not change over time with nabilone. Study 3: Baseline levels of the late-stage lipid-peroxidation marker, 4-hydroxynonenal (4-HNE) were associated with agitation severity cross-sectionally, and longitudinally. However changes in 4-HNE were not associated with changes in agitation severity in either phase. Study 4: The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α) was associated with agitation severity cross-sectionally. Lower baseline and decreases in TNF-α were associated with decreases in agitation severity in the nabilone phase only. Study 5: Inflammatory cytokines, and markers of OS predicted response to nabilone based on symptoms of verbal and physical agitation, respectively. Findings from the nabilone trial suggest that Cchol, 4-HNE and TNF-α may be useful markers of agitation severity. Additionally, response to nabilone may be influenced by the degree of OS and neuroinflammation a patient may have. As there are no validated biomarkers of agitation, identifying markers of agitation and response would assist in identifying patients who may benefit from treatment with nabilone.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".