Sex and ApoE Genotype Differences in Treatment Response to Two Doses of Intranasal Insulin in Adults with Mild Cognitive Impairment or Alzheimer's Disease
Open accessAbstract
A previous clinical trial demonstrated that four months of treatment with intranasal insulin improves cognition and function for patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), but prior studies suggest that response to insulin treatment may differ by sex and ApoE ε4 carriage. Thus, responder analyses using repeated measures analysis of covariance were completed on the trial's 104 participants with MCI or AD who received either placebo or 20 or 40 IU of insulin for 4 months, administered by a nasal delivery device. Results indicate that men and women with memory impairment responded differently to intranasal insulin treatment. On delayed story memory, men and women showed cognitive improvement when taking 20 IU of intranasal insulin, but only men showed cognitive improvement for the 40 IU dose. The sex difference was most apparent for ApoE ε4 negative individuals. For the 40 IU dose, ApoE ε4 negative men improved while ApoE ε4 negative women worsened. Their ApoE ε4 positive counterparts remained cognitively stable. This sex effect was not detected in functional measures. However, functional abilities were relatively preserved for women on either dose of intranasal insulin compared with men. Unlike previous studies with young adults, neither men nor women taking intranasal insulin exhibited a significant change in weight over 4 months of treatment.
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Craft and colleagues found that short-term intranasal insulin improved cognition and lowered neurotoxic Aβ42 in early AD patients.
“Craft and co-workers investigated insulin resistance in AD7,38 and reported improved cognition in early AD patients and decreased levels of neurotoxic Aβ42 following a short-term treatment with intranasal insulin98.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [98]
The Introduction (page unavailable) reports improved memory and cognitive scores after intranasal insulin in people with early AD or MCI. It says amyloid-β levels may be modulated, but neither the Introduction nor the retrieved passages report a decrease in Aβ42; that part of the claim is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe results of intranasal insulin differed according to gender and apoE genotype.
“The results differed according to gender and apoE genotype98.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [98]
Studies in larger samples of male and female participants with cognitive impairments only yielded sporadic indicators of a sex difference in response to IN insulin.
“studies in larger samples of male and female participants with cognitive impairments only yielded sporadic indicators of a sex difference in the response to IN insulin, 74”
From Intranasal insulin (2021) · cites this paper as [74]
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“Differential effects of insulin by ApoE genotype has also been proposed (112).”
Background
- Authors
- Claxton, A., Baker, L. D., Wilkinson, C. W., Trittschuh, E. H., Chapman, D., Watson, G. S., Cholerton, B., Plymate, S. R., Arbuckle, M., & Craft, S.
- Affiliations
- University of Washington (US)
- Wake Forest University Health Sciences (US)
- VA Puget Sound Health Care System (US)
- Corresponding author
- Craft, Suzanne
- ORCID
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2013-05-21
- Volume
- 35
- Issue
- 4
- Pages
- 789-797
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC4144993
- OpenAlex
- W1553529648
- Cited by
- 215
- References
- 44
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 15 · 2023: 18 · 2022: 23 · 2021: 23 · 2020: 23 · 2019: 27 · 2018: 14 · 2017: 20 · 2016: 14 · 2015: 12 · 2014: 6 · 2013: 5
- FWCI
- 8.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institute on Aging (AG027415, T32AG000258, 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
- MeSH terms
- Administration, Intranasal, Aged, Alzheimer Disease, Body Weight, Female, Genotype, Humans, Hypoglycemic Agents, Insulin, Male, Neuropsychological Tests, Sex Characteristics, Body Mass Index, Treatment Outcome, Apolipoprotein E4, Cognitive Dysfunction
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