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Perfusion imaging and inflammation biomarkers provide complementary information in Alzheimer’s disease

Perfusion imaging and inflammation biomarkers provide complementary information in Alzheimer’s disease
Perfusion imaging and inflammation biomarkers provide complementary information in Alzheimer’s disease
Background: single photon emission tomography (SPECT) can detect early changes in brain perfusion to support the diagnosis of dementia. Inflammation is a driver for dementia progression and measures of inflammation may further support dementia diagnosis.

Objective: in this study, we assessed whether combining imaging with markers of inflammation improves prediction of the likelihood of Alzheimer’s disease (AD).

Methods: we analyzed 91 participants datasets (Institutional Ethics Approval 20/NW/0222). AD biomarkers and markers of inflammation were measured in cerebrospinal fluid. Statistical parametric mapping was used to quantify brain perfusion differences in perfusion SPECT images. Logistic regression models were trained to evaluate the ability of imaging and inflammation markers, both individually and combined, to predict AD.

Results: regional perfusion reduction in the precuneus and medial temporal regions predicted Aβ42 status. Increase in inflammation markers predicted tau and neurodegeneration. Matrix metalloproteneinase-10, a marker of blood-brain barrier regulation, was associated with perfusion reduction in the right temporal lobe. Adenosine deaminase, an enzyme involved in sleep homeostasis and inflammation, was the strongest predictor of neurodegeneration with an odds ratio of 10.3. The area under the receiver operator characteristic curve for the logistic regression model was 0.76 for imaging and 0.76 for inflammation. Combining inflammation and imaging markers yielded an area under the curve of 0.85.

Conclusions: study results showed that markers of brain perfusion imaging and markers of inflammation provide complementary information in AD evaluation. Inflammation markers better predict tau status while perfusion imaging measures represent amyloid status. Combining imaging and inflammation improves AD prediction.
Alzheimer’s disease, SPECT, biomarkers, cerebrospinal fluid, inflammation, perfusion
1387-2877
1317-1327
Michopoulou, Sofia
f21ba2a3-f5d3-4998-801f-1ae72ff5d92c
Prosser, Angus
de1efee5-67f5-478e-8cfa-12a8e78a68e5
Dickson, John
627f7f54-97e9-4cc1-812c-728c3973265d
Guy, Matthew
473bbb88-641b-40a5-b22d-221bc048eeb5
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Kipps, Christopher
e43be016-2dc2-45e6-9a02-ab2a0e0208d5
Perneczky, Robert
637f8d9c-64b1-4f97-a0b4-7e24dc07abb7
Michopoulou, Sofia
f21ba2a3-f5d3-4998-801f-1ae72ff5d92c
Prosser, Angus
de1efee5-67f5-478e-8cfa-12a8e78a68e5
Dickson, John
627f7f54-97e9-4cc1-812c-728c3973265d
Guy, Matthew
473bbb88-641b-40a5-b22d-221bc048eeb5
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Kipps, Christopher
e43be016-2dc2-45e6-9a02-ab2a0e0208d5
Perneczky, Robert
637f8d9c-64b1-4f97-a0b4-7e24dc07abb7

Michopoulou, Sofia, Prosser, Angus, Dickson, John, Guy, Matthew, Teeling, Jessica L. and Kipps, Christopher , Perneczky, Robert (ed.) (2023) Perfusion imaging and inflammation biomarkers provide complementary information in Alzheimer’s disease. Journal of Alzheimer's Disease, 96 (3), 1317-1327. (doi:10.3233/JAD-230726).

Record type: Article

Abstract

Background: single photon emission tomography (SPECT) can detect early changes in brain perfusion to support the diagnosis of dementia. Inflammation is a driver for dementia progression and measures of inflammation may further support dementia diagnosis.

Objective: in this study, we assessed whether combining imaging with markers of inflammation improves prediction of the likelihood of Alzheimer’s disease (AD).

Methods: we analyzed 91 participants datasets (Institutional Ethics Approval 20/NW/0222). AD biomarkers and markers of inflammation were measured in cerebrospinal fluid. Statistical parametric mapping was used to quantify brain perfusion differences in perfusion SPECT images. Logistic regression models were trained to evaluate the ability of imaging and inflammation markers, both individually and combined, to predict AD.

Results: regional perfusion reduction in the precuneus and medial temporal regions predicted Aβ42 status. Increase in inflammation markers predicted tau and neurodegeneration. Matrix metalloproteneinase-10, a marker of blood-brain barrier regulation, was associated with perfusion reduction in the right temporal lobe. Adenosine deaminase, an enzyme involved in sleep homeostasis and inflammation, was the strongest predictor of neurodegeneration with an odds ratio of 10.3. The area under the receiver operator characteristic curve for the logistic regression model was 0.76 for imaging and 0.76 for inflammation. Combining inflammation and imaging markers yielded an area under the curve of 0.85.

Conclusions: study results showed that markers of brain perfusion imaging and markers of inflammation provide complementary information in AD evaluation. Inflammation markers better predict tau status while perfusion imaging measures represent amyloid status. Combining imaging and inflammation improves AD prediction.

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Accepted/In Press date: 24 September 2023
Published date: 21 November 2023
Additional Information: Funding Information: The authors of this study have received research funding by the Institute for Life Sciences at the University of Southampton, the Southampton Academy of Research, Applied Research Collaboration Wessex and the National Institute for Health and Care Research (NIHR301287). The views expressed in this publication are those of the authors and not necessarily those of the funding bodies. Publisher Copyright: © 2023 – The authors. Published by IOS Press.
Keywords: Alzheimer’s disease, SPECT, biomarkers, cerebrospinal fluid, inflammation, perfusion

Identifiers

Local EPrints ID: 486293
URI: http://eprints.soton.ac.uk/id/eprint/486293
ISSN: 1387-2877
PURE UUID: 850b503c-b721-429a-872b-815105b116da
ORCID for Angus Prosser: ORCID iD orcid.org/0000-0003-2705-1222
ORCID for Jessica L. Teeling: ORCID iD orcid.org/0000-0003-4004-7391
ORCID for Christopher Kipps: ORCID iD orcid.org/0000-0002-5205-9712

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Date deposited: 16 Jan 2024 17:51
Last modified: 18 May 2024 01:58

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Contributors

Author: Sofia Michopoulou
Author: Angus Prosser ORCID iD
Author: John Dickson
Author: Matthew Guy
Author: Christopher Kipps ORCID iD
Editor: Robert Perneczky

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