Intranasal insulin improves cognition and modulates β-amyloid in early AD
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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Beta-amyloid plaques are a hallmark of AD that develop in its early stage.
“The beta-amyloid plaques are a hallmark of AD that develop in its early stage (Reger et al., 2008).”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Reger et al., 2008
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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)
- ORCID
- 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
- Update notices
- correction (2008-09-09)
- 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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