The noradrenergic system in agitation in Alzheimer's disease
Research type
Research Study
Full title
Does the central noradrenergic system play a role in agitation in Alzheimer's disease?
IRAS ID
264128
Contact name
Kathy Liu
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2019/07/66, UCL Data Protection
Duration of Study in the UK
2 years, 11 months, 26 days
Research summary
This MRC-funded project aims to study whether early changes in a small brain structure called the locus coeruleus (LC) is related to having agitation in Alzheimer's disease (AD), with the hope that this could lead to more targeted treatments.
Many individuals with AD, the most common cause of dementia, develop agitation as the condition progresses. Agitation is when someone with dementia shows emotional distress alongside restlessness or aggressive behaviour. It is distressing, difficulty to treat, reduces quality of life for these individuals and their caregivers and frequently leads to hospital or nursing home admission.
The study aims to understand agitation in terms of its underlying neural mechanisms. The LC contains cells that produce a chemical substance called noradrenaline (NA), which plays an important role in controlling emotional and behavioural responses to stress. It is also one of the earliest structures to be affected in AD. To test whether a neurochemical imbalance (specifically, overactivity) of NA in the brain might make an individual with AD more sensitive to emotional stress and more likely to develop agitation, the study will aim to do two things. Firstly, it will measure the structural integrity of the LC using a short MRI scan in participants with mild-moderate AD (who have a range of agitation scores) to see how this relates to their level of agitation. Secondly, on separate testing days, the same group of individuals will be asked to take a single oral dose of propranolol and placebo to see if propranolol improves their performance on three behavioural tasks lasting 30 minutes in total. Their performance will be compared to a control group.
Participants with AD will be recruited from memory clinics in NHS Trusts (including Camden & Islington, Barnet, Enfield and Haringey, and Central North West London) and healthy controls from Join Dementia Research database.
REC name
London - Queen Square Research Ethics Committee
REC reference
19/LO/1825
Date of REC Opinion
4 Dec 2019
REC opinion
Favourable Opinion