Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer’s Disease Biomarkers: A Pilot Clinical Trial
Open accessAbstract
Background: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer’s disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. Objective: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD. Methods: This randomized, double-blind, placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD. Participants received placebo ( n = 12), 40 IU of insulin detemir ( n = 12), or 40 IU of regular insulin ( n = 12) daily for four months, administered with a nasal delivery device. A cognitive battery was administered at baseline and after two and four months of treatment. MRI was administered for all participants and lumbar puncture for a subset ( n = 20) at baseline and four months. The primary outcome was change from baseline to four months on a memory composite (sum of Z scores for delayed list and story recall). Secondary outcomes included: global cognition (Alzheimer’s Disease Assessment Scale-Cognition), daily functioning (Dementia Severity Rating Scale), MRI volume changes in AD-related regions of interest, and cerebrospinal fluid AD markers. Results: The regular insulin treated group had better memory after two and four months compared with placebo ( p < 0.03). No significant effects were observed for the detemir-assigned group compared with the placebo group, or for daily functioning for either group. Regular insulin treatment was associated with preserved volume on MRI. Regular insulin treatment was also associated with reduction in the tau-P181/Aβ 42 ratio. Conclusion: Future research is warranted to examine the mechanistic basis of treatment differences, and to further assess the efficacy and safety of intranasal insulin.
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A device for IN delivery that had been successfully used in previous studies proved unreliable in the first 49 participants because of malfunctions of a newly added electronic timer.
“A device for IN delivery that had been successfully used in previous studies 75,76,107 proved unreliable in the first 49 participants because of malfunctions of a newly added electronic timer.”
From Intranasal insulin (2021) · cites this paper as [75]
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- Authors
- Craft, S., Claxton, A., Baker, L. D., Hanson, A. J., Cholerton, B., Trittschuh, E. H., Dahl, D., Caulder, E., Neth, B., Montine, T. J., Jung, Y., Maldjian, J., Whitlow, C., & Friedman, S.
- Affiliations
- Wake Forest University Health Sciences (US)
- Alkermes (United States) (US)
- University of Washington (US)
- Stanford Medicine (US)
- The University of Texas Southwestern Medical Center (US)
- Seattle Children's Hospital (US)
- Corresponding author
- Craft, Suzanne
- ORCID
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2017-03-29
- Volume
- 57
- Issue
- 4
- Pages
- 1325-1334
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC5409050
- OpenAlex
- W2600568015
- Cited by
- 335
- References
- 33
- Citations by year
- 2026: 13 · 2025: 40 · 2024: 25 · 2023: 47 · 2022: 32 · 2021: 46 · 2020: 49 · 2019: 46 · 2018: 29 · 2017: 8
- FWCI
- 26.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Alzheimer's Association (ZEN-10-173646)
- National Institute on Aging (P30AG049638)
- 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, insulin detemir
- MeSH terms
- Activities of Daily Living, Aged, Alzheimer Disease, Brain, Cognition, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Organ Size, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Treatment Outcome, Nootropic Agents, Insulins
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