A Phase 2 trial of intranasal insulin for Alzheimer’s disease was published online September 12 in the Archives of Neurology. First author Suzanne Craft of the University of Washington, Seattle, previously reported key findings from this double-blind, four-month trial last summer at the International Conference on Alzheimer’s Disease in Honolulu, Hawaii (see ARF related news story).

The Study of Nasal Insulin to Fight Forgetfulness (SNIFF-120) randomized 64 people with mild cognitive impairment, and 40 mild to moderate AD patients, to daily placebo or insulin (20 or 40 international units) through the nose. As reported at ICAD, the lower insulin dose improved delayed memory, and both doses staved off decline in general cognition (measured by ADAS-Cog) and functional abilities (measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living, i.e., ADCS-ADL).

A subset of participants consented to spinal taps for measuring cerebrospinal fluid AD biomarkers, and to fluorodeoxyglucose positron emission tomography (FDG-PET) scans to assess brain glucose usage. On the whole, CSF levels of Aβ42, Aβ40, tau, and tau phosphorylated at position 181P stayed the same in treated participants over the four-month study. In exploratory analyses, correlations between CSF biomarker changes and cognitive measures showed up in the treatment group (low and high doses were pooled), but not in placebo participants. On FDG-PET, metabolism decreased in AD-affected regions (bilateral frontal, right temporal, bilateral occipital, and precuneus/cuneus) in the placebo group more than in the treatment groups.

In collaboration with the Alzheimer's Disease Cooperative Study group led by Paul Aisen at the University of California, San Diego, Craft has applied for National Institute on Aging funds for a larger, 18-month Phase 2B multisite trial testing similar doses of intranasal insulin in MCI and mild AD patients. The proposed study would include cognitive and functional tests, as well as CSF biomarker and imaging endpoints, she told ARF.—Esther Landhuis.

Reference:
Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 12 Sep 2011. Abstract

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  1. As an insulin research scientist of many decades, it is of interest to read the article showing alterations in brain function by nasal insulin. For many years, it has been believed that brain tissue as an obligatory glucose consumer does not require insulin to stimulate glucose uptake. If critical parts of the brain do require insulin for normal function, then the investigator needs to realize that in the human population there is a very broad range of normal basal insulin levels in the blood, ranging from nearly zero to nearly 1 ng/ml fasting. If the symptom-reducing effect is real, then it would behoove an investigator to examine the basal fasting insulin levels in plasma of Alzheimer's patients to see if the disease appears with higher frequency in those subjects with low insulin levels.

    The part of the paper that I did not appreciate was the use of a fluoridated carbohydrate to assess metabolic status. Many people in the U.S. are unaware of what I believe to be toxicity of synthetic fluoride compounds. In my view, that part of the protocol should not have been permitted to be done.

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References

News Citations

  1. Honolulu: Intranasal Insulin Trial Claims Promise in MCI, AD

Paper Citations

  1. . Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38. PubMed.

Other Citations

  1. ADAS-Cog

External Citations

  1. Study of Nasal Insulin to Fight Forgetfulness

Further Reading

Papers

  1. . Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38. PubMed.

News

  1. Honolulu: Intranasal Insulin Trial Claims Promise in MCI, AD

Primary Papers

  1. . Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38. PubMed.