Decision making and dementia: from mechanisms to clinical trials

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For people with dementia and related conditions, the changes in memory and behaviour not only affect quality of life but also survival. We study the causes and potential treatments of the changes in behaviour and thinking that affect people with dementia. Rather than look only at the root cause of disease (which is often not known), we look at what is happening in the human brain to change behaviour. In practical terms this could be a better basis for treatment than trying to reverse the effects of faulty genes or unknown environmental triggers. We work with people with different conditions, including Alzheimer’s disease and frontotemporal lobar degeneration, and those with the risk of dementia because of faulty genes of ageing. Part 1 of the research aims to understand and restore behaviour, including the actions one takes and the decisions that lie behind those actions. Apathy and impulsivity are of particular interest. These two problems paradoxically often come together. They point to a worse prognosis. And they have possible treatments to hand. We use computational models of the brain to study how decisions are made in the brain, about what to do and what not to do. We link these models to actual brain function (physiology) and brain chemistry (pharmacology). With these methods, we explain why people differ in their symptoms and response to treatment. We call this precision medicine: precision not in terms of gene or molecules of the brain, but precision of the chemical, physiological and cognitive processes underlying dementia. Part 2 looks at brain function more closely. We use very big sets of data from collaborations (eg. MRC Dementias Platform UK and BIOFIND consortium), and specialist studies at the CBU (eg. Cambridge Centre for Ageing and Neuroscience and scans from people with Alzheimer’s disease, frontotemporal dementia, Progressive Supranuclear Palsy). We use these data to understand how and when dementia begins, and combine different types of brain scanning to explain the biological causes of dementia in people. This leads naturally to ways to target treatments at those most likely to respond.