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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
Femminella, Grazia Daniela
Livingston, Nicholas R
Raza, Sanara
van der Doef, Thalia
Frangou, Eleni
Love, Sharon
Busza, Gail
Calsolaro, Valeria
Carver, Stefan
Holmes, Clive
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2021-02-17
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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.
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Femminella GD, Livingston NR, Raza S, van der Doef T, Frangou E, Love S, Busza G, Calsolaro V, Carver S, Holmes C, Ritchie CW, Lawrence RM, McFarlane B, Tadros G, Ridha BH, Bannister C, Walker Z, Archer H, Coulthard E, Underwood B, Prasanna A, Koranteng P, Karim S, Junaid K, McGuinness B, Passmore AP, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Tan T, Holscher C, Harrison J, Brooks DJ, Ballard C, Edison P. Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects? Alzheimers Res Ther. 2021 Feb 17;13(1):47. doi: 10.1186/s13195-021-00784-w. PMID: 33597002; PMCID: PMC7890851.
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