JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

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

Suzanne Craft, Laura D Baker, Thomas J Montine, Satoshi Minoshima, G Stennis Watson, Amy Claxton, Matthew Arbuckle, Maureen Callaghan, Elaine Tsai, Stephen R Plymate, Pattie S Green, James Leverenz, Donna Cross, Brooke Gerton
Archives of Neurology 2012, 69 (1): 29-38
21911655

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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