Alzheimer’s Research & Therapy (Feb 2021)
Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer’s subjects?
- Grazia Daniela Femminella,
- Nicholas R. Livingston,
- Sanara Raza,
- Thalia van der Doef,
- Eleni Frangou,
- Sharon Love,
- Gail Busza,
- Valeria Calsolaro,
- Stefan Carver,
- Clive Holmes,
- Craig W. Ritchie,
- Robert M. Lawrence,
- Brady McFarlane,
- George Tadros,
- Basil H. Ridha,
- Carol Bannister,
- Zuzana Walker,
- Hilary Archer,
- Elizabeth Coulthard,
- Ben Underwood,
- Aparna Prasanna,
- Paul Koranteng,
- Salman Karim,
- Kehinde Junaid,
- Bernadette McGuinness,
- Anthony Peter Passmore,
- Ramin Nilforooshan,
- Ajayverma Macharouthu,
- Andrew Donaldson,
- Simon Thacker,
- Gregor Russell,
- Naghma Malik,
- Vandana Mate,
- Lucy Knight,
- Sajeev Kshemendran,
- Tricia Tan,
- Christian Holscher,
- John Harrison,
- David J. Brooks,
- Clive Ballard,
- Paul Edison
Affiliations
- Grazia Daniela Femminella
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- Nicholas R. Livingston
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- Sanara Raza
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- Thalia van der Doef
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- Eleni Frangou
- University of Oxford
- Sharon Love
- University of Oxford
- Gail Busza
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- Valeria Calsolaro
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- Stefan Carver
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- Clive Holmes
- University of Southampton
- Craig W. Ritchie
- University of Edinburgh
- Robert M. Lawrence
- South West London and St George’s Mental Health NHS Trust
- Brady McFarlane
- Southern Health NHS Foundation Trust
- George Tadros
- Heart of England NHS Foundation Trust
- Basil H. Ridha
- Brighton and Sussex University Hospital Trust
- Carol Bannister
- King’s College London
- Zuzana Walker
- Mental Health Unit, St. Margaret’s Hospital
- Hilary Archer
- North Bristol NHS Trust
- Elizabeth Coulthard
- North Bristol NHS Trust
- Ben Underwood
- Cambridgeshire and Peterborough NHS Foundation Trust
- Aparna Prasanna
- Black Country Partnership NHS Foundation Trust
- Paul Koranteng
- Northamptonshire Healthcare NHS Foundation Trust
- Salman Karim
- Lancashire Care NHS Foundation Trust
- Kehinde Junaid
- Nottinghamshire Healthcare NHS Foundation Trust
- Bernadette McGuinness
- Queen’s University Belfast
- Anthony Peter Passmore
- Queen’s University Belfast
- Ramin Nilforooshan
- Surrey and Borders Partnership NHS Foundation Trust
- Ajayverma Macharouthu
- NHS Ayrshire and Arran
- Andrew Donaldson
- NHS Lanarkshire
- Simon Thacker
- Derbyshire Healthcare NHS Foundation Trust
- Gregor Russell
- Bradford District Care NHS Foundation Trust
- Naghma Malik
- North West Boroughs Partnership NHS Foundation Trust
- Vandana Mate
- Cornwall Partnership NHS Foundation Trust
- Lucy Knight
- Somerset Partnership NHS Foundation Trust
- Sajeev Kshemendran
- South Staffordshire and Shropshire Healthcare NHS Foundation Trust
- Tricia Tan
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- Christian Holscher
- Research and Experimental Center, Henan University of Chinese Medicine
- John Harrison
- Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam
- David J. Brooks
- Newcastle University
- Clive Ballard
- University of Exeter Medical School
- Paul Edison
- Division of Neurology, Neurology Imaging Unit, Department of Brain Sciences, Imperial College London
- DOI
- https://doi.org/10.1186/s13195-021-00784-w
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 11
Abstract
Abstract 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.
Keywords
- Alzheimer’s disease
- Insulin resistance
- Magnetic resonance imaging
- Positron emission tomography imaging
