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Memory improvement following induced hyperinsulinemia in Alzheimer’s disease
Abstract
Dementia of the Alzheimer type (DAT) is accompanied by disruption in glucose regulation and utilization that may contribute to its characteristic memory impairment. Increasing glucose availability by raising plasma glucose improves memory in patients with DAT. Such memory improvement is associated with a secondary elevation in plasma insulin levels, raising the question of whether improvement is due to changes in insulin levels, independent of hyperglycemia. Distributions of insulin receptors in the hippocampus and insulin-mediated increases in glucose utilization in entorhinal cortex provide potential mechanisms for such improvement. We show that raising plasma insulin through intravenous infusion while keeping plasma glucose at a fasting baseline level produces striking memory enhancement for patients with DAT. Previous findings of hyperglycemic memory enhancement were also replicated. Patients with DAT also showed abnormal plasma levels of glucoregulatory hormones and metabolites at baseline and during metabolic manipulations. Our findings suggest that neuroendocrine factors play an important role in the pathophysiology of DAT.
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“Neuronal IRs are involved in diverse brain functions including synapse plasticity, learning and memory (Chiu et al., 2008; Craft et al., 1996; Kern et al., 2001; Lee et al., 2005; Park et al., 2000).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Craft et al., 1996
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Metadata
- Authors
- Craft, S., Newcomer, J., Kanne, S., Dagogo-Jack, S., Cryer, P., Sheline, Y., Luby, J., Dagogo-Jack, A., & Alderson, A.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Craft, Suzanne
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1996-01
- Volume
- 17
- Issue
- 1
- Pages
- 123-130
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2101048381
- Cited by
- 538
- References
- 41
- Citations by year
- 2026: 9 · 2025: 32 · 2024: 45 · 2023: 28 · 2022: 21 · 2021: 29 · 2020: 42 · 2019: 25 · 2018: 17 · 2017: 8 · 2016: 8 · 2015: 10 · 2014: 6 · 2013: 17 · 2012: 17
- FWCI
- 12.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k20mh001045-01)
- National Institute on Aging (R01-AG-10880, R01AG010880)
- National Institute of Mental Health (MH-01045)
- National Center for Research Resources (MO1RR00036, M01RR000036)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Alzheimer's disease, hyperinsulinemia, memory impairment, insulin, glucose regulation, hyperglycemia, hippocampus, insulin receptor, entorhinal cortex, glucoregulatory hormones, neuroendocrine factors
- MeSH terms
- Aged, Alzheimer Disease, Fatty Acids, Glucagon, Humans, Hyperglycemia, Hyperinsulinism, Lactates, Memory, Norepinephrine, Psychiatric Status Rating Scales
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