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