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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
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
0924-977X
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
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, 153-159. (doi:10.1016/j.euroneuro.2020.12.013).

Record type: Article

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.

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Accepted/In Press date: 31 December 2020
e-pub ahead of print date: 8 January 2021
Published date: February 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
ORCID for Ruihua Hou: ORCID iD orcid.org/0000-0001-6127-1478
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for Clive Osmond: ORCID iD orcid.org/0000-0002-9054-4655

Catalogue record

Date deposited: 24 Feb 2021 17:32
Last modified: 22 Nov 2021 02:55

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Contributors

Author: Ruihua Hou ORCID iD
Author: Rebecca Beardmore
Author: Clive Holmes ORCID iD
Author: Clive Osmond ORCID iD
Author: Angela Darekar

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