A case-control study of the locus coeruleus degeneration in Alzheimer’s disease
A case-control study of the locus coeruleus degeneration in Alzheimer’s disease
The locus coeruleus (LC) is the major source of noradrenaline, which plays a key role in cognition. We aimed to detect the extent of the LC signal attenuation in Alzheimer's disease (AD) patients using a neuromelanin (NM)-sensitive MRI and how it may correlate with inflammatory and autonomic measures. An individually matched case-control study design was employed. 24 patients with AD and 24 age and gender matched controls with no cognitive impairment were recruited. The primary outcome measure was the LC signal intensity indicated by the LC contrast ratio (CR) and measured by the NM-sensitive MRI. Secondary outcome measures included neuropsychometric tests of cognitive state, peripheral inflammatory and autonomic measures. Conditional logistic regression analysis revealed a significant 22% LC-CR reduction in the AD group compared with the control group. However, there was no statistical significance from inflammatory or autonomic measures. This is the largest individually-matched case-control study to visualise the LC degeneration in AD patients. The study revealed significant LC degeneration which holds promise to stratify patients who may benefit from treatment targeting noradrenergic dysfunction.
Alzheimer's disease, Locus coeruleus, Magnetic resonance imaging, Neuromelanin, Noradrenaline
153-159
Hou, Ruihua
470bdcbc-93a9-4dad-aac5-26d455c34376
Beardmore, Rebecca
4dc4a3c9-036a-47f7-967d-e020021b97e1
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Darekar, Angela
62e6b511-a358-4e5d-a4ea-03890ba7c2c7
February 2021
Hou, Ruihua
470bdcbc-93a9-4dad-aac5-26d455c34376
Beardmore, Rebecca
4dc4a3c9-036a-47f7-967d-e020021b97e1
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Darekar, Angela
62e6b511-a358-4e5d-a4ea-03890ba7c2c7
Hou, Ruihua, Beardmore, Rebecca, Holmes, Clive, Osmond, Clive and Darekar, Angela
(2021)
A case-control study of the locus coeruleus degeneration in Alzheimer’s disease.
European Neuropsychopharmacology, 43, .
(doi:10.1016/j.euroneuro.2020.12.013).
Abstract
The locus coeruleus (LC) is the major source of noradrenaline, which plays a key role in cognition. We aimed to detect the extent of the LC signal attenuation in Alzheimer's disease (AD) patients using a neuromelanin (NM)-sensitive MRI and how it may correlate with inflammatory and autonomic measures. An individually matched case-control study design was employed. 24 patients with AD and 24 age and gender matched controls with no cognitive impairment were recruited. The primary outcome measure was the LC signal intensity indicated by the LC contrast ratio (CR) and measured by the NM-sensitive MRI. Secondary outcome measures included neuropsychometric tests of cognitive state, peripheral inflammatory and autonomic measures. Conditional logistic regression analysis revealed a significant 22% LC-CR reduction in the AD group compared with the control group. However, there was no statistical significance from inflammatory or autonomic measures. This is the largest individually-matched case-control study to visualise the LC degeneration in AD patients. The study revealed significant LC degeneration which holds promise to stratify patients who may benefit from treatment targeting noradrenergic dysfunction.
Text
Manuscript_revised clear version final1612
- Accepted Manuscript
More information
Accepted/In Press date: 31 December 2020
e-pub ahead of print date: 8 January 2021
Published date: February 2021
Additional Information:
Funding Information:
Hou and Beardmore had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Hou, Holmes, Darekar. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Hou. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Hou, Osmond. Obtained funding: Hou. Supervision: Hou, Holmes, Darekar. We would like to thank Laurie Lau from Clinical and Experimental sciences for his help with blood sample analysis, and Chris Everitt, Emma Lewis, James Leighs and Neil O'Brien from the Radiology and Medical Physics departments respectively, for their help with the imaging data collection and processing. Also authors would like to thank all participants for their effort and time for taking part this study. All authors declare that there is no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the work submitted that could inappropriately influence, or be perceived to influence, their work. The study was funded by a grant awarded to Dr Ruihua Hou by Alzheimer's Research UK (grant reference: ARUK-PPG2016A-6). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
The study was funded by a grant awarded to Dr Ruihua Hou by Alzheimer's Research UK (grant reference: ARUK-PPG2016A-6 ).
Publisher Copyright:
© 2021
Keywords:
Alzheimer's disease, Locus coeruleus, Magnetic resonance imaging, Neuromelanin, Noradrenaline
Identifiers
Local EPrints ID: 446868
URI: http://eprints.soton.ac.uk/id/eprint/446868
ISSN: 0924-977X
PURE UUID: b748e74b-1097-47e4-bdd0-14fb4b1eb959
Catalogue record
Date deposited: 24 Feb 2021 17:32
Last modified: 17 Mar 2024 06:13
Export record
Altmetrics
Contributors
Author:
Rebecca Beardmore
Author:
Angela Darekar
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics