Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia
Open accessAbstract
Previous trials have shown promising effects of intranasally administered insulin for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). These trials used regular insulin, which has a shorter half-life compared to long-lasting insulin analogues such as insulin detemir. The current trial examined whether intranasal insulin detemir improves cognition or daily functioning for adults with MCI or AD. Sixty adults diagnosed with MCI or mild to moderate AD received placebo (n = 20), 20 IU of insulin detemir (n = 21), or 40 IU of insulin detemir (n = 19) for 21 days, administered with a nasal drug delivery device. Results revealed a treatment effect for the memory composite for the 40 IU group compared with placebo (p < 0.05). This effect was moderated by APOE status (p < 0.05), reflecting improvement for APOE-ε4 carriers (p < 0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at baseline predicted greater improvement with the 40 IU dose (r = 0.54, p < 0.02). Significant treatment effects were also apparent for verbal working memory (p < 0.03) and visuospatial working memory (p < 0.04), reflecting improvement for subjects who received the high dose of intranasal insulin detemir. No significant differences were found for daily functioning or executive functioning. In conclusion, daily treatment with 40 IU insulin detemir modulated cognition for adults with AD or MCI, with APOE-related differences in treatment response for the primary memory composite. Future research is needed to examine the mechanistic basis of APOE-related treatment differences, and to further assess the efficacy and safety of intranasal insulin detemir.
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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 [107]
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- Authors
- Claxton, A., Baker, L. D., Hanson, A., Trittschuh, E. H., Cholerton, B., Morgan, A., Callaghan, M., Arbuckle, M., Behl, C., & Craft, S.
- Affiliations
- University of Washington (US)
- Wake Forest University Health Sciences (US)
- Oregon Health & Science University (US)
- Corresponding author
- Craft, Suzanne
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2015-02-06
- Volume
- 44
- Issue
- 3
- Pages
- 897-906
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2145577892
- Cited by
- 467
- References
- 50
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 23 · 2023: 41 · 2022: 45 · 2021: 56 · 2020: 55 · 2019: 46 · 2018: 40 · 2017: 56 · 2016: 42 · 2015: 23
- FWCI
- 39.14
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-04-13)
- Open access
- bronze
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institute on Aging (AG000258, P50AG005136)
- 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
- Insulin Detemir, Administration, Intranasal, Alzheimer Disease, Analysis of Variance, Dose-Response Relationship, Drug, Female, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin, Longitudinal Studies, Male, Memory, Short-Term, Mental Status Schedule, Neuropsychological Tests, Psychomotor Disorders, Time Factors, Treatment Outcome, Area Under Curve, Insulin, Long-Acting, Apolipoprotein E4, Cognitive Dysfunction
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