New research grants announced

Preventing depression

Dr Vasiliki Orgeta at University College London has been awarded a senior fellowship to develop a therapy to prevent depression in people with early-stage dementia without the need for drugs. People with dementia are at a higher risk of depressive symptoms, sadness and loss of enjoyment of life. This hinders their ability to perform everyday activities even more, puts them at risk of needing residential earlier than they otherwise would have, and affects their quality of life. There are currently no known effective treatments, as medications such as antidepressants are ineffective and have significant side effects.

A person with both dementia and depression will be struggling with two lots of difficulties. They may find it even harder to remember things and may be more confused or withdrawn. Depression may also worsen behavioural changes in people with dementia, causing aggression, problems sleeping or refusal to eat.

Dr Orgeta will bring together all theoretical knowledge about depression in dementia, and talk to families and people with dementia about their ideas to develop a new intervention. The intervention will be planned in a way that meets their needs closely, offering strategies and support to cope with depressive symptoms. A group of 60 people with dementia and their carers will try out the intervention with the support of a graduate psychologist. This study will find out how feasible it is to recruit people with dementia and their families to take part, and how many sessions participants are able to complete.

Understanding causes

We have funded a PhD student to work in the lab of Dr James Duce at the University of Leeds to study a biochemical process that increases production of amyloid-beta, a hallmark of Alzheimer’s disease. This is produced when the protein APP is split into smaller pieces. This research group discovered that another protein called lactoferrin, which is produced in response to inflammation, can attach to APP and increase the likelihood of it being split up.

The student will use various techniques to investigate how lactoferrin can alter levels of amyloid-beta as well as understand its significance in Alzheimer’s disease. Experiments will range from studying how each protein attaches to the other, through to how they work in individual cells and within a whole brain.

This research will provide greater understanding about how the inflammation that increases the amount of lactoferrin results in the damage to cells seen in Alzheimer’s disease. By the student identifying the exact part of each protein that makes contact with the other protein, it is hoped that new drugs can be developed to block this interaction. A drug that could stop the attachment of lactoferrin to APP could reduce the production of toxic amyloid-beta.

Improving trials

A project grant for £250,000 has been awarded to Professor Nick Fox to help improve the design of secondary prevention trials in Alzheimer’s disease by investigating the role of brain scans. The idea of secondary prevention is to treat people who already have signs of the disease in the brain, but do not show any outward symptoms.

One of the main challenges in designing prevention trials is how to measure whether the drug has worked. Tests of memory and thinking may be affected by temporary improvements in symptoms and so other measures are needed for a clearer result of the potential treatment.

The researchers will make use of a large study called the Dominantly Inherited Alzheimer Network, which follows people who have a genetic link to Alzheimer’s disease and are at higher risk of developing the condition. The researchers will collect brain images from people taking part in this study and use these to determine the best signs to look for when assessing how well the drug in a prevention trial works. They will also work out aspects such as how many scans need to be collected, and at what times throughout these trials, to get the most accurate understanding of the drug.

This project will inform the design of future trials and ensure that the results gained are a genuine representation of how a drug works. This will help us to understand whether any drugs being used in future clinical trials are effective at preventing dementia.