Gaining new insight into the pathogenesis of Alzheimer’s disease: investigating the role of the locus coeruleus using neuromelanin-sensitive MRI


Study ID: 32050
Short Title: Investigating the Locus Coeruleus in Alzheimer's Disease using MRI
Organisation: University Hospital Southampton NHS Foundation Trust
Location: University Hospital Southampton NHS Foundation Trust
Condition: Alzheimer's Disease
Main Specialty: Dementias
Expected End Date: 01/06/2018
Postcode: SO16 6YD
Contact Name: UHS R&D Office
Contact Email: R&Doffice@uhs.nhs.uk
Active: Yes

Inclusion Criteria

1) Male or female > 50 and < 100 years


2) Able and willing to give informed consent for participation in the study


3) Be able to hear, read, write and perform study neuropsychological tests in English.


4) Healthy control subjects: No cognitive impairment with an SMMSE score > 27 or: MCI subjects: meet NIA-AAA criteria for a MCI diagnosis or: AD subjects: meet NINCDS-ADRDA criteria for a diagnosis of Probable AD with an SMMSE score of 20 – 26 at screen (at the discretion of the Principal Investigator)

Exclusion Criteria

1) Unlikely to cooperate in the study, not able to attend scheduled examinations and visits, or not able to follow study instructions.


2) Absence of a reliable study partner (MCI and AD subjects only)


3) Learning and linguistic/communication disabilities


4) History of eye disease (including glaucoma)


5) History of autoimmune disease


6) Current use of medications that have a diastolic effect on pupils


7) Current use of medications with a NA-based mechanism of action, such as selective noradrenaline reuptake inhibitors and α2-adrenoceptor antagonists


8) Current use of non topical steroids or cytokine modulators


9) Vascular disorder (Modified Hachinki Ischaemic Scale score > 4)


10) History of major psychiatric disorder


11) History of alcohol or substance misuse within the last 2 years.

Study summary:

The locus coeruleus (LC) is a tiny nucleus in the brain stem which produces an important chemical substance called noradrenaline (NA). While cognitive decline in Alzheimer Disease (AD) has primarily been related to dysfunction within the cholinergic system, evidence indicates that there is extensive LC degeneration in AD which is among the earliest pathologies. However, most evidence comes from animal and post-mortem studies. The absence of reliable non-invasive direct measures of LC activity in humans remains challenging. Our research group have developed a novel imaging protocol to directly measure LC signal changes using a high-resolution MRI imaging technique, which is different from conventional MRI technique.
The pilot study proposed here aims to test the feasibility of using the proposed imaging technique to detect signal changes within the LC in patients with mild cognitive impairment and AD and matched healthy controls. In addition, the study will also examine the links between LC signal changes and some key biological and physiological measures. Findings from this pilot study will be used to inform a future larger investigation of the role of the LC in individuals with AD and mild cognitive impairment. The proposed work will help us to advance our understanding of the role of the LC in disease progression of AD. This will also help us to identify new detection markers to assist diagnosis and new treatment for patients with AD in the near future.


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