The Alzheimer’s Association International Conference 2015 have suggested new ways to predict who will develop Alzheimer’s disease, the most common cause of dementia, before symptoms appear. The research highlights a range of potential different tools for detecting the disease early, including a saliva test, measurements of a protein in cerebrospinal fluid (CSF), scans to spot inflammation in the brain or a combination of multiple tests.
Dr Eric Karran, Director of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said:
“The earliest physical changes in the brain associated with Alzheimer’s disease take place long before people begin to experience symptoms such as memory loss. The ability to pick up signs of the disease early would be a real boost for research, as it’s thought that any new treatments will be more effective if they can be given before too much damage has taken place. A test to accurately identify Alzheimer’s at this early stage would allow the right people to take part in clinical trials for new treatments, and could also be vital for helping monitor whether treatments designed to stop the progress of the disease are having the desired effect.
“To be sure any potential test is accurate enough to be useful as a tool for detecting or diagnosing Alzheimer’s, it’s essential to follow up early-stage research like this with larger studies that track people over time. It’s important to note that the tests being explored here would not currently be suitable to help diagnose Alzheimer’s in the clinic.”
Brain scans, cerebrospinal fluid and memory tests may predict mild cognitive impairment
In one study, researchers at Johns Hopkins University in the US evaluated how well a variety of tests were able to predict the onset of mild cognitive impairment (MCI) – problems with memory and thinking that are not severe enough to be classed as dementia. People with MCI are at an increased risk of developing Alzheimer’s or another form of dementia. The research looked at data from 189 people, none of whom had cognitive problems at the start of the study, who were followed for up to five years. The results showed six tests combined were best able to predict who would develop MCI during the course of the study: two different memory tests, measurements of two protein levels in CSF, and MRI scans to measure two separate brain regions.
Dr Karran said:
“It’s very likely that a combination of measurements will be the best way to identify Alzheimer’s early, but further work will be needed to improve the accuracy of the combined set of tests used here. As not all people with MCI develop Alzheimer’s disease, follow up work to determine which of the people in this study were later diagnosed with Alzheimer’s would be a helpful next step.”
Saliva test may detect Alzheimer’s, mild cognitive impairment and healthy ageing
A second study, from researchers at the University of Alberta in Canada, looked at the potential of molecules in saliva to predict Alzheimer’s disease. The researchers collected saliva samples from 22 people with Alzheimer’s, 25 people with MCI and 35 people with no cognitive problems, and measured the levels of different metabolites – byproducts of biochemical reactions in the body. They found that certain metabolites tended to be higher or lower in the saliva of each group, with different ‘patterns’ of metabolite levels in people without memory problems, those with MCI and those with Alzheimer’s. When they looked for these patterns in saliva samples from another group of 27 people, the researchers were able to predict which people had Alzheimer’s or MCI.
Dr Karran said:
“The use of saliva to detect disease is an attractive idea, as such a test would be relatively cheap, non-invasive and easy to carry out, but additional studies in large groups of people will be needed to demonstrate whether the test outlined here holds promise. Metabolites can offer a wealth of information about what may be happening inside cells, and studies such as this may also provide further clues to help understand the disease process.”
Protein in cerebrospinal fluid may help detect Alzheimer’s disease
Meanwhile, new research from VU University in Amsterdam suggests that a protein called neurogranin in CSF may be useful for predicting whether a person will develop Alzheimer’s disease. The study saw researchers measure levels of neurogranin – which is found in the brain and is involved in helping cells to communicate – in the CSF of 163 people, once at the start of the study and again two years later. When the study began, 65 of the group had Alzheimer’s, 61 had MCI and 37 had no cognitive problems. The results showed that at the start of the study, neurogranin levels tended to be higher in people with Alzheimer’s, and levels of the protein were also raised in people with MCI who were later diagnosed with Alzheimer’s disease. Over time, people with MCI and Alzheimer’s saw no change in neurogranin levels, while those without memory problems had a slight increase in the protein by the end of the study.
Dr Karran said:
“The measurement of proteins in cerebrospinal fluid has proved a useful approach in the past for early detection of disease, with levels of two known Alzheimer’s proteins in the fluid already identified as possible markers of the disease. This study adds to some previous research suggesting that neurogranin in cerebrospinal fluid may be higher in Alzheimer’s, but it will be important for these results to be confirmed in much larger groups to know whether the protein could help predict the onset of Alzheimer’s.”
Progress in research to develop scans for brain inflammation
Researchers from the Imaging Neuroinflammation in Neurodegenerative Diseases (INMIND) consortium argue that brain scans to pick up inflammation could play a key role in detecting Alzheimer’s disease in future. Recent research has suggested that in Alzheimer’s disease, microglia – the brain’s immune cells – may become overactive and cause further damage to the brain. Outlining research to improve the ability of PET scans to detect brain inflammation, the scientists suggest that these scans could be useful in future for monitoring how treatments for the disease affect microglia.
Dr Karran said:
“A growing body of evidence points to a potential role for inflammation in driving the development of Alzheimer’s disease, and many research efforts are now focused on trying to understand this process. The ability to visualise inflammation in the brain is key for investigating how this response is involved in Alzheimer’s, as well as for tracking the effectiveness of potential treatments designed to target inflammation. Scans that could more easily pick up these changes in the brain would be a step forward for this research, and it’s positive that progress is being made in this area.”