Send to:

Choose Destination
See comment in PubMed Commons below
Arch Neurol. 2012 Jan;69(1):29-38. doi: 10.1001/archneurol.2011.233. Epub 2011 Sep 12.

Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial.

Author information

  • 1Geriatric Research, Education, and Clinical Center, S-182, Veterans Affairs Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA.



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).


Randomized, double-blind, placebo-controlled trial.


Clinical research unit of a Veterans Affairs medical center.


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).


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.


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.


These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD. Trial Registration Identifier: NCT00438568.

Comment in

[PubMed - indexed for MEDLINE]
Free PMC Article

Publication Types, MeSH Terms, Substances, Secondary Source ID, Grant Support

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Write to the Help Desk