Modulation of memory by insulin and glucose: Neuropsychological observations in Alzheimer’s disease

Watson, G.Stennis; Craft, Suzanne

doi:10.1016/j.ejphar.2004.02.048

Cited by 307Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMemory and Neural Mechanisms

Modulation of memory by insulin and glucose: Neuropsychological observations in Alzheimer’s disease

Watson, G.Stennis, Craft, Suzanne·2004·European Journal of Pharmacology

DOI 10.1016/j.ejphar.2004.02.048

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Abstract

Converging evidence has identified a potential association among Alzheimer's disease, glucose metabolism, insulin activity, and memory. Notably, type 2 diabetes, which is characterized by insulin resistance, may modulate the risk of Alzheimer's disease, and patients with Alzheimer's disease may have a greater risk for glucoregulatory impairments than do healthy older adults. In animal studies, it has been shown that raising blood glucose levels acutely can facilitate memory, in part, by increasing cholinergic activity, which is greatly diminished in patients with Alzheimer's disease. Other studies have confirmed that glucose administration can facilitate memory in healthy humans and in patients with Alzheimer's disease. Interestingly, glucose effects on memory appear to be modulated by insulin sensitivity (efficiency of insulin-mediated glucose disposal). Of course, the acute effects of glucose administration should be distinguished from the effects of chronic hyperglycemia (diabetes), which has been associated with cognitive impairments, at least in older adults. The relationship of insulin and memory has been more difficult to characterize. In animals, systemic insulin administration has been associated with memory deficits, likely due, in part, to hypoglycemia that occurs when exogenous insulin is not supplemented with glucose to maintain euglycemia. In healthy adults and patients with Alzheimer's disease, raising plasma insulin levels while maintaining euglycemia can improve memory; however, raising plasma glucose while suppressing endogenous insulin secretion may not improve memory, suggesting that adequate levels of insulin and glucose are necessary for memory facilitation. Clinical studies have corroborated findings that patients with Alzheimer's disease are more likely than healthy older adults to have reduced insulin sensitivity, and further suggest that apolipoprotein E genotype may modulate the effects of insulin on glucose disposal, memory facilitation, and amyloid precursor protein processing. Collectively, these findings support an association among Alzheimer's disease, impaired glucose metabolism, and reduced insulin sensitivity.

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Authors: Watson, G. S., & Craft, S.
Affiliations: University of Washington (US)
Corresponding author: Craft, Suzanne
ORCID: Craft, Suzanne
Venue: European Journal of Pharmacology
Publisher: Elsevier BV
Published: 2004-04
Volume: 490
Issue: 1-3
Pages: 97-113
ISSN: 0014-2999 (ISSN-L)
DOI: 10.1016/j.ejphar.2004.02.048
OpenAlex: W2043629385
Semantic Scholar: 25e784ce91a1cb9676a15481a925fb57df3e284c
Cited by: 307
References: 143
Citations by year: 2026: 2 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 13 · 2020: 11 · 2019: 14 · 2018: 8 · 2017: 7 · 2016: 12 · 2015: 15 · 2014: 25 · 2013: 20 · 2012: 21
FWCI: 2.83
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: European Journal of Pharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs
National Institutes of Health
National Institute on Aging (R01-AG-10880, R01AG010880)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061606, R01 DK 61606)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: Alzheimer's disease, insulin, glucose, memory, insulin resistance, type 2 diabetes, hyperglycemia, insulin sensitivity, glucose metabolism, cholinergic activity, apolipoprotein E, APP processing, hypoglycemia, normoglycemia, cognitive impairment
MeSH terms: Alzheimer Disease, Animals, Blood Glucose, Glucose, Humans, Insulin, Memory

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Modulation of memory by insulin and glucose: Neuropsychological observations in Alzheimer’s disease

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