Neurodegenerative diseases present a significant health, social, and economic burden. Disease-modifying therapies and effective preventive strategies are lacking. Treatment trials are typically conducted after symptoms have emerged, which may be too late in the disease process to alter its course.
Researchers from Cambridge have demonstrated that individuals may exhibit signs of brain impairment as early as nine years before they are diagnosed with one of several dementia-related disorders. The results suggest that at-risk patients may be tested in the future to help determine which ones may benefit from interventions to lower their chance of getting one of the illnesses or to help identify people suitable for enrollment in clinical trials for new treatments.
For the study, scientists analyzed data from the UK Biobank, a biomedical database and research resource containing anonymized genetic, lifestyle and health information from half a million UK participants aged 40-69. As well as collecting information on participants’ health and disease diagnoses, 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 the number of falls. The team found impairment in several areas, such as problem-solving and number recall, across various conditions.
Regarding problem-solving exercises, reaction times, recalling lists of numbers, prospective memory (our capacity to remember to do something later), and pair matching, people who developed Alzheimer’s disease performed worse than healthy people. This was also true for individuals who experienced frontotemporal dementia, a more uncommon form of dementia.
People who developed Alzheimer’s were more likely than healthy adults to have had a fall in the previous 12 months. Those patients who developed a rare neurological condition known as progressive supranuclear palsy (PSP), which affects balance, were more than twice as likely as healthy individuals to have had a fall.
Patients reported poorer overall health at baseline for every condition studied – including Parkinson’s disease and dementia with Lewy bodies.
First author Nol Swaddiwudhipong, a junior 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 several 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. Rittman said the findings could also help identify people who can participate in clinical trials for potential new treatments. “The problem with clinical trials is that by necessity, they often recruit patients with a diagnosis, but we know that by this point, they are already some way down the road, and their condition cannot be stopped. If we can find these individuals early enough, we’ll have a better chance of seeing if the drugs are effective.”
- Swaddiwudhipong, N, et al. Pre-Diagnostic Cognitive and Functional Impairment in Multiple Sporadic Neurodegenerative Diseases. Alzheimer’s & Dementia; 13 Oct 2022; DOI: 10.1002/alz.12802