Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial
Open accessAbstract
OBJECTIVE: To examine the effects of intranasal insulin administration on cognition, function, cerebral glucose metabolism, and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease (AD). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Clinical research unit of a Veterans Affairs medical center. PARTICIPANTS: The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment (n = 64) or mild to moderate AD (n = 40). Intervention Participants received placebo (n = 30), 20 IU of insulin (n = 36), or 40 IU of insulin (n = 38) for 4 months, administered with a nasal drug delivery device (Kurve Technology, Bothell, Washington). MAIN OUTCOME MEASURES: Primary measures consisted of delayed story recall score and the Dementia Severity Rating Scale score, and secondary measures included the Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-cog) score and the Alzheimer's Disease Cooperative Study-activities of daily living (ADCS-ADL) scale. A subset of participants underwent lumbar puncture (n = 23) and positron emission tomography with fludeoxyglucose F 18 (n = 40) before and after treatment. RESULTS: Outcome measures were analyzed using repeated-measures analysis of covariance. Treatment with 20 IU of insulin improved delayed memory (P < .05), and both doses of insulin (20 and 40 IU) preserved caregiver-rated functional ability (P < .01). Both insulin doses also preserved general cognition as assessed by the ADAS-cog score for younger participants and functional abilities as assessed by the ADCS-ADL scale for adults with AD (P < .05). Cerebrospinal fluid biomarkers did not change for insulin-treated participants as a group, but, in exploratory analyses, changes in memory and function were associated with changes in the Aβ42 level and in the tau protein-to-Aβ42 ratio in cerebrospinal fluid. Placebo-assigned participants showed decreased fludeoxyglucose F 18 uptake in the parietotemporal, frontal, precuneus, and cuneus regions and insulin-minimized progression. No treatment-related severe adverse events occurred. CONCLUSIONS: These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD. Trial Registration clinicaltrials.gov Identifier: NCT00438568.
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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 [76]
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- Authors
- Craft, S.
- Affiliations
- VA Puget Sound Health Care System (US)
- Corresponding author
- Craft, Suzanne
- ORCID
- Craft, Suzanne
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2012-01-01
- Volume
- 69
- Issue
- 1
- Pages
- 29
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3260944
- OpenAlex
- W2153284686
- Cited by
- 1,253
- References
- 32
- Citations by year
- 2026: 47 · 2025: 63 · 2024: 66 · 2023: 70 · 2022: 70 · 2021: 82 · 2020: 82 · 2019: 105 · 2018: 92 · 2017: 101 · 2016: 94 · 2015: 91 · 2014: 105 · 2013: 100 · 2012: 75
- FWCI
- 62.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Nancy and Buster Alvord Endowment (AG05136)
- University of Washington
- National Institute on Aging (AG027415, T32AG000258, P50AG005136, R01AG027415)
- NIH Clinical Center
- 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, memory preservation, functional capacity, brain glucose metabolism, cerebrospinal fluid biomarkers, amyloid-beta 42, tau protein, activities of daily living, dementia severity, intranasal drug delivery, veterans, treatment-emergent adverse events, treatment discontinuation
- MeSH terms
- Administration, Intranasal, Aged, Alzheimer Disease, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Hospitals, Veterans, Humans, Hypoglycemic Agents, Immunoassay, Insulin, Male, Neuropsychological Tests, Peptide Fragments, Pilot Projects, Psychiatric Status Rating Scales, Spinal Puncture, Least-Squares Analysis, Amyloid beta-Peptides, tau Proteins, Fluorodeoxyglucose F18, Positron-Emission Tomography, Cognitive Dysfunction
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