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. 2021 Feb 17;13(1):47.
doi: 10.1186/s13195-021-00784-w.

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

Grazia Daniela Femminella  1 , Nicholas R Livingston  1 , Sanara Raza  1 , Thalia van der Doef  1 , Eleni Frangou  2 , Sharon Love  2 , Gail Busza  1 , Valeria Calsolaro  1 , Stefan Carver  1 , Clive Holmes  3 , Craig W Ritchie  4 , Robert M Lawrence  5 , Brady McFarlane  6 , George Tadros  7 , Basil H Ridha  8 , Carol Bannister  9 , Zuzana Walker  10 , Hilary Archer  11 , Elizabeth Coulthard  11 , Ben Underwood  12 , Aparna Prasanna  13 , Paul Koranteng  14 , Salman Karim  15 , Kehinde Junaid  16 , Bernadette McGuinness  17 , Anthony Peter Passmore  17 , Ramin Nilforooshan  18 , Ajayverma Macharouthu  19 , Andrew Donaldson  20 , Simon Thacker  21 , Gregor Russell  22 , Naghma Malik  23 , Vandana Mate  24 , Lucy Knight  25 , Sajeev Kshemendran  26 , Tricia Tan  1 , Christian Holscher  27 , John Harrison  28 , David J Brooks  29 , Clive Ballard  30 , Paul Edison  31
Affiliations

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

Grazia Daniela Femminella et al. Alzheimers Res Ther. .

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.

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Conflict of interest statement

The other authors have nothing to declare in relation to this manuscript.

Figures

Fig. 1
Fig. 1
Multiple linear regression between HOMA2, hippocampal rCMRGlc and total grey matter volume. a The inverse association between log transformed HOMA2 hippocampal rCMRGlc, in a multiple regression model corrected by age and gender (R2 = 0.19, p = 0.01). Log transformed HOMA2 was negatively associated with total grey matter volumes (R2 = 0.37, p = 0.01), in a multiple regression model corrected by age and gender (b). rCMRGlc is expressed in μmol/g/min, total grey matter volumes are expressed in mm3
See this image and copyright information in PMC

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