Monday March 10 2014
Could new tests make diagnosing dementia easier?
“Blood test that can predict Alzheimer's,” was the headline used by BBC News, the Daily Mail and The Guardian today. Similar coverage was seen across many of the front pages of other newspapers.
These headlines reflected new research showing how a simple blood test may be able to detect early signs of cognitive decline and mild Alzheimer’s disease.
US researchers discovered a panel of 10 biomarkers that, with 90% accuracy, could distinguish people who would progress to have either mild cognitive impairment or mild Alzheimer’s disease within two to three years, from those who wouldn’t.
While promising, the results were only based on a small group of adults over 70 years old who were studied over five years. Of those who developed mild cognitive impairment or mild Alzheimer’s disease, only 28 people had the test. Consequently, it is not clear if the test has any predictive power in the wider population, is applicable to younger adults, or can predict the disease more than two to three years in advance.
The Daily Mail outlined how, while the research was a breakthrough, experts had warned it would bring “ethical concerns”. This is an important point, because there is currently no cure for Alzheimer’s disease, so some people may prefer not to know they might get it. The current unrefined test means at least one in 10 would be wrongly told they will go on to develop the condition, given the severity of the disease, this may cause significant needless worry.
Where did the story come from?
The study was carried out by researchers from a range of US Universities and Medical institutions and was funded by the US National Institutes of Health.
The study was published in the peer-reviewed medical journal, Nature Medicine.
The media reporting was generally balanced, with many highlighting the clear ethical question of whether there is any benefit in telling people they are likely to develop a serious condition that currently has no cure. Most media sources correctly acknowledged the need for more research to confirm the usefulness of the test, and that a useable test may be many years away.
However, while this research is exciting, it is still in an early stage and so front page coverage in four national newspapers is perhaps a little over-the-top.
What kind of research was this?
This was a cohort study looking to see if a blood test could detect Alzheimer’s disease before symptoms developed.
Alzheimer’s disease causes a progressive dementia. It affects more than 35 million individuals worldwide and is expected to affect 115 million by 2050.
There are currently no cures for the disease and no treatments to improve symptoms to any significant degree. This is because, at the moment, it is only possible to diagnose Alzheimer’s when symptoms such as memory loss show up. Unfortunately, this is usually long after the brain has deteriorated at a cellular level, meaning the disease is well underway by the time it is diagnosed.
Current tests for detecting early disease involve invasive medical treatments, which are also time consuming and often expensive. Discovering new tests and treatments targeting early stages of Alzheimer’s, before any outwardly obvious symptoms occur (known as pre-clinical disease), is a hot topic for research. Theoretically, detecting the disease early on will enable more options to be used to stop or slow down the progress of the disease.
What did the research involve?
The researchers recruited a group of people aged 70 or over and analysed their blood and recorded their cognitive abilities over the next five years for signs of decline. The researchers’ examined participants’ blood samples to see if anything in the blood could be used to predict who among the cognitively normal group would develop mental impairment problems and who would not.
The researchers enrolled 525 people over the five years and subjected them to a number of questionnaires to assess their mental health, including memory, verbal reasoning, attention, functional capacities. Based on this they were divided into two groups:
- a healthy control group showing “normal” cognitive abilities
- a group with memory problems at the start of the study, defined as amnestic mild cognitive impairment (aMCI) or mild Alzheimer’s disease (AD)
The control group was selected to match the memory-impaired group on the basis of age, sex and education.
The analysis investigated how people’s mental health scores changed after each year during a five year follow up period. Specifically, they wanted to know how many healthy controls went on to develop aMCI or mild Alzheimer’s disease. The main analysis looked for differences in the blood samples of people who went on to develop aMCI or AD and those that did not.
What were the basic results?
The researchers analysed 126 blood samples, including from 18 people who had developed aMCI or mild Alzheimer’s disease during the study period. The blood tests pointed towards a way of distinguishing between those that would develop cognitive impairment and those that would not.
After further investigation, the researchers found a set of 10 lipids (fats) in the blood could predict the conversion of people with normal cognitive abilities to either amnestic mild cognitive impairment or Alzheimer’s disease within a two to three year timeframe with more than 90% accuracy.
Once they had the panel of 10 fats that predicted disease development, they tested it on a further group of 41 participants to validate their results. This included 10 people who developed aMCI or mild Alzheimer’s disease during the study period. Similar results were found, confirming the initial findings.
The sensitivity and specificity of the test in the validation experiments was 90%.
How did the researchers interpret the results?
Based on the biochemical tests, the researchers believed the panel of 10 blood fats detected may reflect a worsening of cell membrane integrity contributing to the disease. They concluded the panel of 10 lipids could act as a test that may provide an indication of early deterioration of brain function in the pre-clinical stage of Alzheimer’s disease (when the person does not yet have symptoms).
The researchers said they had found and validated a way of assessing blood samples that distinguish cognitively normal participants who will progress to have either aMCI or AD within two to three years from those who won’t. They said that their defined panel of markers featured biochemicals that have essential structural and functional roles in the integrity and functionality of cell membranes.
This small cohort study has presented a collection of 10 biomarkers that predicted with 90% accuracy 28 cognitively normal participants who progressed to have either aMCI or mild Alzheimer’s disease within two to three years compared to those who did not.
This represents a proof-of-concept that an easily administered blood test may provide a way of detecting Alzheimer’s disease at a pre-clinical stage.
The main limitation to bear in mind when interpreting this study is the relatively older group (over 70) and short predictive range investigated. This means the test was only able to detect who would develop cognitive decline in the next two to three years. For that reason, the study does not provide any information on whether the test can predict the disease any earlier, for example by testing the blood of people in their 50s. This will inevitably be the subject of further study.
The Daily Mail outlines how “experts called the breakthrough a real step forward, but warn it will bring with it ethical concerns”. This is an important point to consider because there is currently no cure for Alzheimer’s disease.
As The Independent put it, “Would anyone welcome being told that they are going to develop – and very likely die from – an incurable disorder that will eventually rob them of their memories, emotions and personality over a period of many years?”
The reaction to the news will certainly be different for different individuals, but could be emotionally and psychologically damaging for some.
Along a similar line, the current test was 90% accurate. This means at least one in 10 will be wrongly told they will go on to develop the condition, causing needless worry.
The researchers cannily point out that the test “requires external validation using similar rigorous clinical classification before further development for clinical use. Such additional validation should be considered in a more diverse demographic group than our initial cohort”.
Ultimately, this research provides proof-of-concept that a blood test may predict early stage Alzheimer’s disease, but it’s too early to say whether this test in particular is definitely effective, or could soon be used in mainstream clinical practice. Time, and more research, will tell.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.