Do glial‐reactivity and cerebral blood flow modulate cerebral glucose metabolism in Alzheimer’s disease?

Abstract Background Alzheimer’s disease is a devastating neurodegenerative disorder with a complex pathogenesis. One main pathological feature utilised in diagnosis is neurodegeneration or neuronal injury, which is reflected in reductions in cerebral glucose metabolism measured by [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET). Here we evaluated the involvement of glial reactivity measured with magnetic resonance spectroscopy (MRS) and cerebral blood flow measured with arterial spin labelling (ASL) on [18F]FDG PET as a measure of cerebral glucose metabolism. Method 123 people living with early Alzheimer’s disease who completed baseline evaluations on the evaluating liraglutide in Alzheimer’s disease trial were enrolled. Participants completed [18F]FDG PET scans with arterial input, T1 weighted MRI, single‐voxel 1 HMRS, and pulsed ASL scans at Imperial College London Clinical Imaging Facility. The Totally Automatic Robust Quantitation in NMR (TARQUIN) package was used to process MRS scans and identify the concentration of myo‐inositol within the posterior cingulate cortex (PCC), a marker of glial activation. Oxford‐ASL was utilised to process ASL and quantify cerebral blood flow in the PCC. Finally, spectral analysis was performed on the [18F]FDG PET scans to assess the cerebral metabolic rate of glucose in the PCC. Result Pearson’s correlations were performed between the cerebral metabolic rate of glucose, cerebral blood flow and glial activity measured by the level of myo‐inositol in the PCC. Increased cerebral glucose metabolism was correlated with higher myo‐inositol in this sample of Alzheimer’s disease participants. In contrast, cerebral blood flow was not associated with cerebral glucose metabolism. Conclusion Here we demonstrate that increased glial reactivity contributes to [18F]FDG PET signal in the early stages of Alzheimer’s disease. In response to early neuronal injury, astrocytes and microglia may become activated and enhance regional rates of glucose consumption. Hence, the contribution from these cells in addition to neurons should be considered in interpreting [18F]FDG PET as a measure of cerebral glucose metabolism. Interestingly, cerebral blood flow did not influence glucose metabolism. Microglia and astrocyte reactivity may contribute to an increase the cerebral glucose metabolism while neuronal loss and synaptic function may contribute to lower glucose metabolism measured by [18F]FDG in the early stages of Alzheimer's disease.

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Journal
Alzheimer s & Dementia
Published
2024-12-01
DOI
https://doi.org/10.1002/alz.088897
Primary Topic
Advanced MRI Techniques and Applications
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article
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article

Do glial‐reactivity and cerebral blood flow modulate cerebral glucose metabolism in Alzheimer’s disease?

Elizabeth Coulthard, Rainer Hinz, Salman Karim, Benjamin R. Underwood et al.
Alzheimer s & Dementia
Advanced MRI Techniques and Applications
article

Do glial‐reactivity and cerebral blood flow modulate cerebral glucose metabolism in Alzheimer’s disease?

Elizabeth Coulthard, Rainer Hinz, Salman Karim, Benjamin R. Underwood, Sajeev Kshemendran, Ramin Nilforooshan, Basil H. Ridha, Clive Ballard, Paul Edison, Robert Lawrence, Paul Koranteng, Bernadette McGuinness, Grazia Daniela Femminella, John Harrison, Kehinde Junaid, Brady McFarlane, Naghma Malik, George Tadros, Clive Holmes, Karen A. Ritchie, Christian Hölscher, Simon Thacker, Zuzana Walker, Gregor Russell, Hilary Archer, Vandana Mate, Anthony Peter Passmore, Aparna Prasanna, Lucy Knight, Joseph Nowell
article en

Abstract

Abstract Background Alzheimer’s disease is a devastating neurodegenerative disorder with a complex pathogenesis. One main pathological feature utilised in diagnosis is neurodegeneration or neuronal injury, which is reflected in reductions in cerebral glucose metabolism measured by [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET). Here we evaluated the involvement of glial reactivity measured with magnetic resonance spectroscopy (MRS) and cerebral blood flow measured with arterial spin labelling (ASL) on [18F]FDG PET as a measure of cerebral glucose metabolism. Method 123 people living with early Alzheimer’s disease who completed baseline evaluations on the evaluating liraglutide in Alzheimer’s disease trial were enrolled. Participants completed [18F]FDG PET scans with arterial input, T1 weighted MRI, single‐voxel 1 HMRS, and pulsed ASL scans at Imperial College London Clinical Imaging Facility. The Totally Automatic Robust Quantitation in NMR (TARQUIN) package was used to process MRS scans and identify the concentration of myo‐inositol within the posterior cingulate cortex (PCC), a marker of glial activation. Oxford‐ASL was utilised to process ASL and quantify cerebral blood flow in the PCC. Finally, spectral analysis was performed on the [18F]FDG PET scans to assess the cerebral metabolic rate of glucose in the PCC. Result Pearson’s correlations were performed between the cerebral metabolic rate of glucose, cerebral blood flow and glial activity measured by the level of myo‐inositol in the PCC. Increased cerebral glucose metabolism was correlated with higher myo‐inositol in this sample of Alzheimer’s disease participants. In contrast, cerebral blood flow was not associated with cerebral glucose metabolism. Conclusion Here we demonstrate that increased glial reactivity contributes to [18F]FDG PET signal in the early stages of Alzheimer’s disease. In response to early neuronal injury, astrocytes and microglia may become activated and enhance regional rates of glucose consumption. Hence, the contribution from these cells in addition to neurons should be considered in interpreting [18F]FDG PET as a measure of cerebral glucose metabolism. Interestingly, cerebral blood flow did not influence glucose metabolism. Microglia and astrocyte reactivity may contribute to an increase the cerebral glucose metabolism while neuronal loss and synaptic function may contribute to lower glucose metabolism measured by [18F]FDG in the early stages of Alzheimer's disease.

Alzheimer s & DementiaVol. 20(S2)
Queen's University Belfast (GB), North Bristol NHS Trust (GB), University of Exeter (GB), University of Cambridge (GB), Heart of England NHS Foundation Trust (GB), Southern Health NHS Foundation Trust (GB), Nottinghamshire Healthcare NHS Foundation Trust (GB), University of Manchester (GB), University of Bristol (GB), South West London and St George's Mental Health NHS Trust (GB), North West Boroughs Healthcare NHS Foundation Trust (GB), Shropshire Community Health NHS Trust (GB), Derbyshire Community Health Services NHS Foundation Trust (GB), UK Dementia Research Institute (GB), Northamptonshire Healthcare NHS Foundation Trust (GB), Bradford District Care NHS Foundation Trust (GB), Black Country Partnership NHS Foundation Trust (GB), Lancashire Care NHS Foundation Trust (GB), Cornwall Partnership NHS Foundation Trust (GB), Amsterdam University Medical Centers (NL), Somerset Partnership NHS Foundation Trust (GB), University of Southampton (GB), University College London (GB), Imperial College London (GB), Surrey and Borders Partnership NHS Foundation Trust (GB), Lancaster University (GB), Vrije Universiteit Amsterdam (NL), University of Edinburgh (GB)
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