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 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

doi:10.1186/s13195-021-00784-w

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 journal › Article (Academic Journal) › peer-review

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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.

Original language	English
Article number	47 (2021)
Number of pages	12
Journal	Alzheimer's Research and Therapy
Volume	13
DOIs	https://doi.org/10.1186/s13195-021-00784-w
Publication status	Published - 17 Feb 2021

Keywords

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

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Femminella, G. D., Livingston, N. R., Raza, S., van der Doef, T., Frangou, E., Love, S., Busza, G., Calsolaro, V., Carver, S., Holmes, C., Ritchie, C. W., Lawrence, R. M., McFarlane, B., Tadros, G., Ridha, B. H., Bannister, C., Walker, Z., Archer, H., Coulthard, E., ... Edison, P. (2021). Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects? Alzheimer's Research and Therapy, 13, [47 (2021)]. https://doi.org/10.1186/s13195-021-00784-w

@article{112bdb5305b24790a354bebef20cb0a6,

title = "Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?",

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{\textquoteright}s disease, Insulin resistance, Magnetic resonance imaging, Positron emission tomography imaging",

author = "Femminella, {Grazia Daniela} and Livingston, {Nicholas R} and Sanara Raza and {van der Doef}, Thalia and Eleni Frangou and Sharon Love and Gail Busza and Valeria Calsolaro and Stefan Carver and Clive Holmes and Ritchie, {Craig W} and Lawrence, {Robert M} and Brady McFarlane and George Tadros and Ridha, {Basil H} and Carol Bannister and Zuzana Walker and Hilary Archer and Elizabeth Coulthard and Ben Underwood and Aparna Prasanna and Paul Koranteng and Salman Karim and Kehinde Junaid and Bernadette McGuinness and Passmore, {Anthony Peter} and Ramin Nilforooshan and Ajayverma Macharouthu and Andrew Donaldson and Simon Thacker and Gregor Russell and Naghma Malik and Vandana Mate and Lucy Knight and Sajeev Kshemendran and Tricia Tan and Christian Holscher and John Harrison and Brooks, {David J} and Clive Ballard and Paul Edison",

year = "2021",

month = feb,

day = "17",

doi = "10.1186/s13195-021-00784-w",

language = "English",

volume = "13",

journal = "Alzheimer's Research and Therapy",

issn = "1758-9193",

publisher = "BioMed Central",

}

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 2021, 'Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?', Alzheimer's Research and Therapy, vol. 13, 47 (2021). https://doi.org/10.1186/s13195-021-00784-w