학술논문
Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer’s subjects?
Document Type
article
Author
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
Source
Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-11 (2021)
Subject
Language
English
ISSN
1758-9193
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.