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

TY - JOUR

T1 - Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer’s subjects?

AU - Femminella, Grazia Daniela

AU - Livingston, Nicholas R.

AU - Raza, Sanara

AU - van der Doef, Thalia

AU - Frangou, Eleni

AU - Love, Sharon

AU - Busza, Gail

AU - Calsolaro, Valeria

AU - Carver, Stefan

AU - Holmes, Clive

AU - Ritchie, Craig W.

AU - Lawrence, Robert M.

AU - McFarlane, Brady

AU - Tadros, George

AU - Ridha, Basil H.

AU - Bannister, Carol

AU - Walker, Zuzana

AU - Archer, Hilary

AU - Coulthard, Elizabeth

AU - Underwood, Ben

AU - Prasanna, Aparna

AU - Koranteng, Paul

AU - Karim, Salman

AU - Junaid, Kehinde

AU - McGuinness, Bernadette

AU - Passmore, Anthony Peter

AU - Nilforooshan, Ramin

AU - Macharouthu, Ajayverma

AU - Donaldson, Andrew

AU - Thacker, Simon

AU - Russell, Gregor

AU - Malik, Naghma

AU - Mate, Vandana

AU - Knight, Lucy

AU - Kshemendran, Sajeev

AU - Tan, Tricia

AU - Holscher, Christian

AU - Harrison , John

AU - Brooks, David J.

AU - Ballard, Clive

AU - Edison, Paul

N1 - Funding Information: This article presents independent research sponsored by Imperial College London and supported by the NIHR, CRF, and BRC at the Imperial College Healthcare NHS Trust. The views expressed are those of the authors and not necessarily those of Imperial College London, the NHS, the NIHR, or the Department of Health. We thank the Imperial College Clinical Imaging Facility for providing MRI and PET imaging facilities. 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. Funding Information: This article presents independent research sponsored by Imperial College London and supported by the NIHR, CRF, and BRC at the Imperial College Healthcare NHS Trust. The views expressed are those of the authors and not necessarily those of Imperial College London, the NHS, the NIHR, or the Department of Health. We thank the Imperial College Clinical Imaging Facility for providing MRI and PET imaging facilities. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/12

Y1 - 2021/12

N2 - BackgroundType 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.MethodsIn 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.ResultsIn 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.ConclusionsIn 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.

AB - BackgroundType 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.MethodsIn 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.ResultsIn 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.ConclusionsIn 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.

UR - http://www.scopus.com/inward/record.url?scp=85100880873&partnerID=8YFLogxK

U2 - 10.1186/s13195-021-00784-w

DO - 10.1186/s13195-021-00784-w

M3 - Article

SN - 1758-9193

VL - 13

JO - Alzheimer's Research and Therapy

JF - Alzheimer's Research and Therapy

IS - 1

M1 - 47

ER -