Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?


BACKGROUND: Type 2 diabetes is a risk factor for Alzheimer's disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects. METHODS: In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function. RESULTS: In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs. CONCLUSIONS: In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.

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Divisions: College of Health & Life Sciences > Aston Medical School
Additional Information: © The Author(s). 2021 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data. Funding Information: This study was funded by Alzheimer’s Drug Discovery Foundation, US, Alzheimer’s Society, UK, Novo Nordisk A/S, Van Geest Foundation, NIHR Biomedical Research Centre, Imperial College London and Kings College London. Dr. Edison was funded by the Medical Research Council and now by the Higher Education Funding Council for England (HEFCE). He has also received grants from Alzheimer’s Research, UK, Alzheimer’s Drug Discovery Foundation, Alzheimer’s Society, UK, Novo Nordisk, GE Healthcare, Astra Zeneca, Pfizer, Eli Lilly and Piramal Life Sciences.
Uncontrolled Keywords: Alzheimer Disease,Insulin Resistance,Magnetic Resonance Imaging,Positron-Emission Tomography Imaging
Publication ISSN: 1758-9193
Last Modified: 06 Jun 2024 07:18
Date Deposited: 18 Oct 2022 15:08
Full Text Link:
Related URLs: https://alzres. ... 195-021-00784-w (Publisher URL)
PURE Output Type: Article
Published Date: 2021-02-17
Accepted Date: 2021-02-03
Authors: Femminella, Grazia Daniela
Livingston, Nicholas R
Raza, Sanara
van der Doef, Thalia
Frangou, Eleni
Love, Sharon
Busza, Gail
Calsolaro, Valeria
Carver, Stefan
Holmes, Clive
Ritchie, Craig W
Lawrence, Robert M
McFarlane, Brady
Tadros, George (ORCID Profile 0000-0001-5820-7643)
Ridha, Basil H
Bannister, Carol
Walker, Zuzana
Archer, Hilary
Coulthard, Elizabeth
Underwood, Ben
Prasanna, Aparna
Koranteng, Paul
Karim, Salman
Junaid, Kehinde
McGuinness, Bernadette
Passmore, Anthony Peter
Nilforooshan, Ramin
Macharouthu, Ajayverma
Donaldson, Andrew
Thacker, Simon
Russell, Gregor
Malik, Naghma
Mate, Vandana
Knight, Lucy
Kshemendran, Sajeev
Tan, Tricia
Holscher, Christian
Harrison, John
Brooks, David J
Ballard, Clive
Edison, Paul



Version: Published Version

License: Creative Commons Attribution

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