Dementia signs identified up to nine years before diagnosis

Signs of brain impairment can be identified up to nine years before dementia-related diseases are diagnosed, researchers report today.

Researchers from the University of Cambridge say their findings could mean at-risk patients could be screened to identify individuals who might benefit from interventions to reduce their risk – or to enrol suitable candidates into clinical trials for new treatments.

There are very few effective treatments for dementia or other neurodegenerative diseases because these conditions are often diagnosed once symptoms appear.

However, the underlying neurodegeneration is likely to have begun years, or even decades, earlier.

To see if it is possible to detect changes in brain function before the onset of symptoms, the research team, which also included colleagues at Cambridge University Hospitals NHS Foundation Trust collected data from half a million participants in the UK Biobank, aged between 40 and 69.

UK Biobank collected data from a battery of tests including problem solving, memory, reaction times and grip strength, as well as data on weight loss and gain and on the number of falls, which allowed the team to look back to see whether any signs were present at baseline.

Their findings are published in *Alzheimer’s & Dementia*.

After analysing the data, they identified impairment in several areas, with people who went on to develop Alzheimer’s disease scoring more poorly in problem solving tasks, reaction times, remembering lists of numbers, prospective memory and pair matching compared to healthy individuals.

They found similar results among individuals who developed frontotemporal dementia.

People who went on to develop Alzheimer’s were more likely than healthy adults to have had a fall in the previous 12 months, while individuals who developed progressive supranuclear palsy (PSP) were more than twice as likely as healthy individuals to have had a fall.

The team found that in every condition they studied, including Parkinson’s disease and dementia with Lewy bodies, individuals reported poorer overall health at baseline.

First author Dr Nol Swaddiwudhipong, a trainee doctor at the University of Cambridge, said: "When we looked back at patients’ histories, it became clear that they were showing some cognitive impairment several years before their symptoms became obvious enough to prompt a diagnosis.

"The impairments were often subtle, but across a number of aspects of cognition. This is a step towards us being able to screen people who are at greatest risk – for example, people over 50 or those who have high blood pressure or do not do enough exercise – and intervene at an earlier stage to help them reduce their risk."�

Senior author Dr Tim Rittman, from the Department of Clinical Neurosciences at the University of Cambridge, added: "People should not be unduly worried if, for example, they are not good at recalling numbers. Even some healthy individuals will naturally score better or worse than their peers. But we would encourage anyone who has any concerns or notices that their memory or recall is getting worse to speak to their GP."�

Dr Richard Oakley, Associate Director of Research at Alzheimer’s Society said: "This important study builds on other research funded by Alzheimer’s Society and suggests that for some people who go on to develop Alzheimer’s disease, memory and thinking problems can begin up to nine years before they receive a diagnosis.

"This opens up the possibility of screening programmes in the future to help identify people at risk and who may benefit from interventions and identify more people suitable for clinical trials for new dementia treatments, which are both so desperately needed."�

Swaddiwudhipong, N, et al. Pre-Diagnostic Cognitive and Functional Impairment in Multiple Sporadic Neurodegenerative Diseases. *Alzheimer’s & Dementia* 13 October 2022


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