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Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia

Article type: Research Article

Authors: Claxton, Amya; b | Baker, Laura D.c | Hanson, Angelaa; b | Trittschuh, Emily H.a; b | Cholerton, Brennab | Morgan, Amya; b | Callaghan, Maureena; b | Arbuckle, Matthewd | Behl, Colina; b | Craft, Suzannec; *

Affiliations: [a] Geriatric Research, Education, & Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA | [b] Department of Psychiatry & Behavioral Science, University of Washington School of Medicine, Seattle, Washington, USA | [c] Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA | [d] Department of Psychiatry, Oregon Health and Science University, Portland, Oregon, USA

Correspondence: [*] Correspondence to: Suzanne Craft, PhD, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1207, USA. Tel.: +1 336 713 8832; Fax: +1 336 713 8800; E-mail: suzcraft@wakehealth.edu.

Keywords: Alzheimer's disease, clinical trials, randomized, insulin, intranasal drug administration, mild cognitive impairment

DOI: 10.3233/JAD-141791

Journal: Journal of Alzheimer's Disease, vol. 44, no. 3, pp. 897-906, 2015

Accepted 29 September 2014
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Published: 6 February 2015
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Supplementary Materials:

Supplementary Tables.

Abstract

Previous trials have shown promising effects of intranasally administered insulin for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). These trials used regular insulin, which has a shorter half-life compared to long-lasting insulin analogues such as insulin detemir. The current trial examined whether intranasal insulin detemir improves cognition or daily functioning for adults with MCI or AD. Sixty adults diagnosed with MCI or mild to moderate AD received placebo (n = 20), 20 IU of insulin detemir (n = 21), or 40 IU of insulin detemir (n = 19) for 21 days, administered with a nasal drug delivery device. Results revealed a treatment effect for the memory composite for the 40 IU group compared with placebo (p < 0.05). This effect was moderated by APOE status (p < 0.05), reflecting improvement for APOE-ε4 carriers (p < 0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at baseline predicted greater improvement with the 40 IU dose (r = 0.54, p < 0.02). Significant treatment effects were also apparent for verbal working memory (p < 0.03) and visuospatial working memory (p < 0.04), reflecting improvement for subjects who received the high dose of intranasal insulin detemir. No significant differences were found for daily functioning or executive functioning. In conclusion, daily treatment with 40 IU insulin detemir modulated cognition for adults with AD or MCI, with APOE-related differences in treatment response for the primary memory composite. Future research is needed to examine the mechanistic basis of APOE-related treatment differences, and to further assess the efficacy and safety of intranasal insulin detemir.

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