P3–276: Long‐acting Intranasal Insulin Detemir Improves Working Memory for Adults with Mild Cognitive Impairment or Early‐stage Alzheimer's Dementia

Previous clinical trials have yielded promising effects of intranasally administered insulin for adults diagnosed with Alzheimer's disease dementia (AD) or mild cognitive impairment (MCI)[1–3]. These trials used regular insulin, which has a short half life and mimics post prandial release. The insulin analogue detemir, in contrast, has a longer half life and mimics basal insulin secretion, and it may have better parenchymal penetration and greater cognitive benefit. In a recent study, we hypothesized that intranasal insulin detemir would improve cognition for adults with MCI or AD, and report here results for secondary outcome measures of working memory. Participants with AD (n = 20) or amnestic MCI (n = 38) were randomized to receive placebo (n=19), 20 IU (n=20), or 40 IU (n=19) intranasal insulin detemir daily for 21 days. A cognitive battery was administered at baseline and day 21. Verbal working memory was measured using Dot Counting N-back, in which participants were asked to count targets on consecutive computer displays. After n -number of displays, subjects recall the number of targets presented on previous displays. Visual working memory was assessed using the Benton Visual Retention Test (BVRT), an object recognition memory paradigm that activates the dentate gyrus [4]. For this task, subjects first view a design and then identify this design included in an array containing four distractors, three of which are highly similar to the target. Scores for each of the two insulin detemir dose groups were compared with the placebo group using repeated measures analysis of covariance (ANCOVA). Age, diagnosis, MMSE score, gender, and APOE-e4 allele status were examined as covariates. Significant treatment effects were apparent for Dot Counting N-Back (p=0.03) and BVRT (p=0.04); relative to placebo, subjects who received the 40 IU dose of intranasal insulin determir showed improved visual working memory from baseline to day 21. No significant differences were noted for subjects who received the 20 IU dose vs. placebo.