Evidence mapPaperPMID 34101779Full record

Trial reportThe journal of prevention of Alzheimer's disease

Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer's Disease.

D Kellar, S N Lockhart, P Aisen, R Raman, R A Rissman, J Brewer, S Craft

2 registry-linked trialsOpen access · diamondAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in The journal of prevention of Alzheimer's disease. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT06072963. Cited by 55 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 3 pooled it
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06072963 phase2recruiting

Combination of Intranasal Insulin With Oral Semaglutide to Improve Cognition and Cerebral Blood Flow: a Feasibility Study

Ran2024Enrolled80Registered outcomes15Posted comparisons0ConditionsAlzheimer Disease, Metabolic Syndrome, Mild Cognitive ImpairmentArmsIntranasal insulin, Intranasal insulin placebo, semaglutide, Semaglutide placebo
Open the trial in the graph
NCT01767909 phase2 / phase3completednot on this map

Therapeutic Effects of Intranasally-Administered Insulin in Adults With Amnestic Mild Cognitive Impairment (aMCI) or Mild Alzheimer's Disease (AD)

TypeinterventionalSponsorUniversity of Southern CaliforniaRan2014 to 2018Enrolled240ConditionsAmnestic Mild Cognitive Impairment, Alzheimer's DiseaseArmsInsulin (Humulin® R U-100), Placebo
3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 3 syntheses or guidelines pooled it, 78 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. A phase 2A/B randomized trial of metabolic modulators intranasal insulin and empagliflozin for MCI and early AD.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  6. Trial
  7. Trial
  8. Review
  9. Longitudinal Changes in White Matter Hypointensities in Recurrent Late-Life Depression.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2026
    Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Traumatic Brain Injury and Coenzyme Q10: An Overview.International journal of molecular sciences · 2025
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

D KellarSuzanne Craft, PhD, Department of Internal Medicine-Geriatrics, Wake Forest School of Medicine, One Medical Center Boulevard, Winston-Salem, NC 27157, suzcraft@wakehealth.edu.
S N Lockhart
P Aisen
R Raman
R A Rissman
J Brewer
S Craft
Wake Forest University · USSouthern States University · USUniversity of California, San Diego · USUniversity of Southern California · US

Funding

REC CoreP30AG072947 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$3.0M
NIA NIH HHS P30 AG072947NIA NIH HHS RF1 AG041845
6 · The paper itself

Abstract

backgroundIntranasally administered insulin has shown promise in both rodent and human studies in Alzheimer's disease; however, both effects and mechanisms require elucidation.

objectiveWe assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer's disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909).

designA randomized (1:1) double-blind clinical trial.

settingTwelve sites across the United States.

participantsAdults with mild cognitive impairment or Alzheimer's disease.

interventionParticipants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled. MEASUREMENTS: Changes from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer's Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale, and a memory composite.

resultsThe insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer's disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group.

conclusionIntranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin's potential as a therapeutic option for Alzheimer's disease.

Indexed as

Activities of Daily LivingAdministration, IntranasalAgedAlzheimer DiseaseBiomarkersBrainCognitionCognitive DysfunctionFemaleHumansHypoglycemic AgentsImage Processing, Computer-AssistedInsulinInsulin, Regular, HumanMagnetic Resonance ImagingMaleBiomarkersHypoglycemic AgentsInsulinInsulin, Regular, HumanAlzheimer’s diseaseclinical trialCSFintranasal insulinwhite matter

Identifiers

PMID34101779
PMCPMC10233712
OpenAlexW3149522138

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.