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 UnderwoodAparna 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*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

32 Citations (Scopus)
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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.

Original languageEnglish
Article number47 (2021)
Number of pages12
JournalAlzheimer's Research and Therapy
Publication statusPublished - 17 Feb 2021


  • Alzheimer’s disease
  • Insulin resistance
  • Magnetic resonance imaging
  • Positron emission tomography imaging


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