Cerebrospinal fluid insulin concentration increases and correlates with memory improvements after intranasal insulin administration
Bibliographic record
Abstract
Abstract Background There are currently no effective treatments for Alzheimer’s disease (AD) which has prompted research into alternative therapeutic options; one such promising option is intranasal insulin (INI). Although INI treatment over 4 months improved memory, no study has verified whether INI administration elevates insulin in the central nervous system and whether elevations are accompanied by enhanced memory performance. Method This study examined the effect of acute INI administration on cerebrospinal fluid (CSF) insulin levels and memory measured by the auditory‐verbal learning task (AVLT) in mild cognitive impairment (MCI, n=11, mean age=68+‐4.8) and cognitively unimpaired adults (n=8, age=67.5+‐4.1). Participants were randomized to receive insulin (Humulin‐R 20 IU) or placebo at their first visit using an intranasal delivery device and returned two‐to‐six weeks later to repeat the visit with the other substance. Fasting participants underwent a blood draw, INI or placebo administration, AVLT, lumbar puncture (LP), blood draw, and delayed AVLT. CSF and plasma insulin measured with ultra‐sensitive ELISA and AVLT scores were compared between placebo and insulin visits. Linear modeling was performed in SAS with visit as a repeated factor and covariates BMI, cognitive status, sex, age, race, and Montreal Cognitive Assessment (MOCA) score. Non‐contributory covariates (p>0.15) were removed. Result CSF insulin concentration increased after INI administration (p<0.05) while peripheral insulin levels remained unchanged. INI also trended to increased AVLT immediate recall (p<0.1). CSF insulin concentration changes and AVLT changes were positively correlated (p< 0.05). Participants with higher baseline MOCA scores showed greater increases in CSF insulin after INI relative to placebo administration (p<0.05). Conclusion INI is effectively transported into the CNS without modulating peripheral levels. In the brain, insulin may act to increase cognition in a concentration‐dependent manner. INI may be a good therapeutic option for adults with MCI or AD for whom CSF insulin levels are enhanced through intranasal delivery.
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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) | 0.000 | 0.000 |
| 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 | 0.000 |
| 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".