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Clinical Trials
Jan 2012

Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial

Author Affiliations

Author Affiliations: Geriatric Research, Education, and Clinical Center (Drs Craft, Baker, Watson, Claxton, Callaghan, and Plymate and Mr Arbuckle) and Mental Illness Research, Education, and Clinical Center (Drs Leverenz and Gerton), Veterans Affairs Puget Sound Health Care System, and Departments of Psychiatry and Behavioral Sciences (Drs Craft, Baker, Watson, Claxton, and Leverenz), Pathology (Dr Montine), Radiology (Drs Minoshima and Cross), Medicine (Drs Tsai, Plymate, and Green), and Neurology (Drs Leverenz and Gerton), University of Washington School of Medicine, Seattle, Washington.

Arch Neurol. 2012;69(1):29-38. doi:10.1001/archneurol.2011.233

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