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

Femminella, Grazia Daniela, Livingston, Nicholas R, Raza, Sanara, van der Doef, Thalia, Frangou, Eleni, Love, Sharon, Busza, Gail, Calsolaro, Valeria, Carver, Stefan, Holmes, Clive, Ritchie, Craig W, Lawrence, Robert M, McFarlane, Brady, Tadros, George, Ridha, Basil H, Bannister, Carol, Walker, Zuzana, Archer, Hilary, Coulthard, Elizabeth, Underwood, Ben, Prasanna, Aparna, Koranteng, Paul, Karim, Salman, Junaid, Kehinde, McGuinness, Bernadette, Passmore, Anthony Peter, Nilforooshan, Ramin, Macharouthu, Ajayverma, Donaldson, Andrew, Thacker, Simon, Russell, Gregor, Malik, Naghma, Mate, Vandana, Knight, Lucy, Kshemendran, Sajeev, Tan, Tricia, Holscher, Christian, Harrison, John, Brooks, David J, Ballard, Clive and Edison, Paul (2021) Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects? Alzheimer's research & therapy, 13 (1). p. 47. ISSN 1758-9193. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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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.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: WK Endocrine system. Endocrinology
WM Psychiatry. Mental health
Divisions: Emergency Services > Elderly
Related URLs:
Depositing User: Mrs Yolande Brookes
Date Deposited: 25 Feb 2021 11:34
Last Modified: 25 Feb 2021 11:34
URI: http://www.repository.uhblibrary.co.uk/id/eprint/4010

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