TY - JOUR
T1 - Intranasal insulin improves cognition and modulates β-amyloid in early AD
AU - Reger, M. A.
AU - Watson, G. S.
AU - Green, P. S.
AU - Wilkinson, C. W.
AU - Baker, L. D.
AU - Cholerton, B.
AU - Fishel, M. A.
AU - Plymate, S. R.
AU - Breitner, J. C.S.
AU - DeGroodt, W.
AU - Mehta, P.
AU - Craft, S.
N1 - Funding Information:
Supported by the Department of Veterans Affairs, the Institute for the Study on Aging, and National Institute on Aging RO1 AG027415.
PY - 2008/2/5
Y1 - 2008/2/5
N2 - Background: Reduced brain insulin signaling and low CSF-to-plasma insulin ratios have been observed in patients with Alzheimer disease (AD). Furthermore, intracerebroventricular or IV insulin administration improve memory, alter evoked potentials, and modulate neurotransmitters, possibly by augmenting low brain levels. After intranasal administration, insulin-like peptides follow extracellular pathways to the brain within 15 minutes. Objective: We tested the hypothesis that daily intranasal insulin treatment would facilitate cognition in patients with early AD or its prodrome, amnestic mild cognitive impairment (MCI). The proportion of verbal information retained after a delay period was the planned primary outcome measure. Secondary outcome measures included attention, caregiver rating of functional status, and plasma levels of insulin, glucose, j3-amyloid, and cortisol. Methods: Twenty-five participants were randomly assigned to receive either placebo (n = 12) or 20 IU BID intranasal insulin treatment (n = 13) using an electronic atomizer, and 24 participants completed the study. Participants, caregivers, and all clinical evaluators were blinded to treatment assignment. Cognitive measures and blood were obtained at baseline and after 21 days of treatment. Results: Fasting plasma glucose and insulin were unchanged with treatment. The insulin-treated group retained more verbal information after a delay compared with the placebo-assigned group (p = 0.0374). Insulin-treated subjects also showed improved attention (p = 0.0108) and functional status (p = 0.0410). Insulin treatment raised fasting plasma concentrations of the short form of the j3-amyloid peptide (A/340; p = 0.0471) without affecting the longer isoform (A/342), resulting in an increased A/340/42 ratio (p = 0.0207). Conclusions: The results of this pilot study support further investigation of the benefits of intranasal insulin for patients with Alzheimer disease, and suggest that intranasal peptide administration may be a novel approach to the treatment of neurodegenerative disorders. Neurology® 2008;70:440-448.
AB - Background: Reduced brain insulin signaling and low CSF-to-plasma insulin ratios have been observed in patients with Alzheimer disease (AD). Furthermore, intracerebroventricular or IV insulin administration improve memory, alter evoked potentials, and modulate neurotransmitters, possibly by augmenting low brain levels. After intranasal administration, insulin-like peptides follow extracellular pathways to the brain within 15 minutes. Objective: We tested the hypothesis that daily intranasal insulin treatment would facilitate cognition in patients with early AD or its prodrome, amnestic mild cognitive impairment (MCI). The proportion of verbal information retained after a delay period was the planned primary outcome measure. Secondary outcome measures included attention, caregiver rating of functional status, and plasma levels of insulin, glucose, j3-amyloid, and cortisol. Methods: Twenty-five participants were randomly assigned to receive either placebo (n = 12) or 20 IU BID intranasal insulin treatment (n = 13) using an electronic atomizer, and 24 participants completed the study. Participants, caregivers, and all clinical evaluators were blinded to treatment assignment. Cognitive measures and blood were obtained at baseline and after 21 days of treatment. Results: Fasting plasma glucose and insulin were unchanged with treatment. The insulin-treated group retained more verbal information after a delay compared with the placebo-assigned group (p = 0.0374). Insulin-treated subjects also showed improved attention (p = 0.0108) and functional status (p = 0.0410). Insulin treatment raised fasting plasma concentrations of the short form of the j3-amyloid peptide (A/340; p = 0.0471) without affecting the longer isoform (A/342), resulting in an increased A/340/42 ratio (p = 0.0207). Conclusions: The results of this pilot study support further investigation of the benefits of intranasal insulin for patients with Alzheimer disease, and suggest that intranasal peptide administration may be a novel approach to the treatment of neurodegenerative disorders. Neurology® 2008;70:440-448.
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U2 - 10.1212/01.WNL.0000265401.62434.36
DO - 10.1212/01.WNL.0000265401.62434.36
M3 - Article
C2 - 17942819
AN - SCOPUS:40349091597
SN - 0028-3878
VL - 70
SP - 440
EP - 448
JO - Neurology
JF - Neurology
IS - 6
ER -