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Intranasal insulin in Alzheimer’s dementia or mild cognitive impairment: a systematic review


Background and aims

Due to common pathophysiological findings of Alzheimer’s disease (AD) with diabetes mellitus (DM), insulin has been suggested as a possible treatment of AD or mild cognitive impairment (MCI). A safe alternative of IV insulin is intranasal (IN) insulin. The aim of this systematic review is to investigate the effects of IN insulin on cognitive function of patients with either AD or MCI.


A literature search of the electronic databases Medline, Scopus and CENTRAL was performed to identify RCTs investigating the effect of IN insulin administration on cognitive tasks, in patients with AD or MCI.


Seven studies (293 patients) met our inclusion criteria. Most studies showed that verbal memory and especially story recall was improved after IN insulin administration. Sometimes the effect was restricted for apoe4 (−) patients. Intranasal insulin did not affect other cognitive functions. However, there were some positive results in functional status and daily activity. Data suggested that different insulin types and doses may have different effects on different apoe4 groups. In addition, the effects of treatment on Αβ levels differed from study to study. Finally, IN insulin resulted in minor adverse effects.


Intranasal insulin improved story recall performance of apoe4 (−) patients with AD or MCI. Other cognitive functions were not affected, but there were some positive results in functional status and daily activity. Since IN insulin is a safe intervention, future studies should be conducted with larger doses and after proper selection of patients and insulin types.

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Author information

KLA: Study concept, design and writing of the manuscript (including tables). GK: Data collection process (literature search, flow diagram and data extraction from the included studies). AM: Data collection process (literature search, flow diagram and data extraction from the included studies). DK: Assessment of risk of bias of the included studies (including the respective figures of “Risk of bias”). PM: Contribution to methodology and design of the study, helped with the disagreements of literature search and data extraction which were originally conducted by Dr. Kalaitzidis and Dr. Malli, reviewed the initial draft. VSL: Critical revision of the manuscript for important intellectual content, approval of the paper.

Correspondence to Konstantinos Ioannis Avgerinos.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.


This study was not sponsored by any company. Dr. Avgerinos reports no disclosures. Dr. Kalaitzidis reports no disclosures. Dr. Malli reports no disclosures. Dr. Kalaitzoglou reports no disclosures. Dr. Myserlis reports no disclosures. Dr. Lioutas reports no disclosures.

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Avgerinos, K.I., Kalaitzidis, G., Malli, A. et al. Intranasal insulin in Alzheimer’s dementia or mild cognitive impairment: a systematic review. J Neurol 265, 1497–1510 (2018). https://doi.org/10.1007/s00415-018-8768-0

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  • Alzheimer’s disease
  • MCI (mild cognitive impairment)
  • Cognitive function
  • Intranasal insulin
  • Systematic review