Cited by 830Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

Intranasal insulin improves cognition and modulates β-amyloid in early AD

Reger, M. A., Watson, G. S., Green, P. S., Wilkinson, C. W., Baker, L. D., Cholerton, B., Fishel, M. A., Plymate, S. R. +4 more·2008·Neurology

Abstract

BACKGROUND: Reduced brain insulin signaling and low CSF-to-plasma insulin ratios have been observed in patients with Alzheimer disease (AD). Furthermore, intracerebroventricular or IV insulin administration improve memory, alter evoked potentials, and modulate neurotransmitters, possibly by augmenting low brain levels. After intranasal administration, insulin-like peptides follow extracellular pathways to the brain within 15 minutes. OBJECTIVE: We tested the hypothesis that daily intranasal insulin treatment would facilitate cognition in patients with early AD or its prodrome, amnestic mild cognitive impairment (MCI). The proportion of verbal information retained after a delay period was the planned primary outcome measure. Secondary outcome measures included attention, caregiver rating of functional status, and plasma levels of insulin, glucose, beta-amyloid, and cortisol. METHODS: Twenty-five participants were randomly assigned to receive either placebo (n = 12) or 20 IU BID intranasal insulin treatment (n = 13) using an electronic atomizer, and 24 participants completed the study. Participants, caregivers, and all clinical evaluators were blinded to treatment assignment. Cognitive measures and blood were obtained at baseline and after 21 days of treatment. RESULTS: Fasting plasma glucose and insulin were unchanged with treatment. The insulin-treated group retained more verbal information after a delay compared with the placebo-assigned group (p = 0.0374). Insulin-treated subjects also showed improved attention (p = 0.0108) and functional status (p = 0.0410). Insulin treatment raised fasting plasma concentrations of the short form of the beta-amyloid peptide (A beta 40; p = 0.0471) without affecting the longer isoform (A beta 42), resulting in an increased A beta 40/42 ratio (p = 0.0207). CONCLUSIONS: The results of this pilot study support further investigation of the benefits of intranasal insulin for patients with Alzheimer disease, and suggest that intranasal peptide administration may be a novel approach to the treatment of neurodegenerative disorders.

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Crossref · 10.1212/01.wnl.0000265401.62434.36

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Authors
Reger, M. A., Watson, G. S., Green, P. S., Wilkinson, C. W., Baker, L. D., Cholerton, B., Fishel, M. A., Plymate, S. R., Breitner, J. C. S., DeGroodt, W., Mehta, P., & Craft, S.
Affiliations
University of Washington (US)
Venue
Neurology
Published
2008-02-05
Volume
70
Issue
6
Pages
440-448
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
OpenAlex
W2083337622
Cited by
830
References
31
Citations by year
2026: 21 · 2025: 24 · 2024: 37 · 2023: 38 · 2022: 34 · 2021: 49 · 2020: 29 · 2019: 52 · 2018: 55 · 2017: 47 · 2016: 36 · 2015: 49 · 2014: 63 · 2013: 50 · 2012: 52
FWCI
26.74
Type
journal article
Language
en
Open access
closed
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (R01AG027415)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
intranasal insulin, Alzheimer's disease, amnestic mild cognitive impairment, early Alzheimer's disease, cognitive function, attention, functional status, amyloid-beta, insulin signaling, plasma insulin, cortisol
MeSH terms
Administration, Intranasal, Aged, Aged, 80 and over, Alzheimer Disease, Attention, Brain, Cognition Disorders, Humans, Insulin, Neuropsychological Tests, Peptide Fragments, Pilot Projects, Verbal Behavior, Amyloid beta-Peptides, Treatment Outcome, Disease Progression, Neuroprotective Agents, Plaque, Amyloid

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