Tuesday, 10 December 2013

Test could give two-year warning for Alzheimer's

Test could give two-year warning for Alzheimer's "New test can give two years' warning of Alzheimer's," reports the Mail Online. The news comes from a small Canadian study that found that a specific change in brain activity seen on MRI testing, combined with certain memory difficulties, was 87.5% accurate at predicting the development of Alzheimer's disease.

The study looked at people with a condition known as mild cognitive impairment (MCI). MCI describes a range of symptoms that impact on cognition and memory, but not to such an extent that it seriously affects a person's day to day life. Some people with MCI will go on to develop Alzheimer's, although it is currently difficult to identify those who would benefit from treatment.
The researchers performed various cognitive tests and an MRI scan on 45 people with MCI and 20 healthy people. They followed both groups over two years and compared the results of the initial tests between those who developed dementia and those who did not.
They found that difficulties with memory retrieval of familiar information, coupled with thinning of the part of the brain associated with various emotional and thinking processes, could predict which people with MCI would go on to develop Alzheimer's disease.
This is not really a new test, as cognitive testing and MRI scans are already part of the diagnostic process for investigating the early signs of dementia.
The findings may help predict which people are at an increased risk of developing Alzheimer's disease, but the study size is too small for the results to change current medical practice. It is likely that these techniques will be used in larger populations to see if the results continue to be accurate. 

Where did the story come from?

The study was carried out by researchers from the University of Montreal and was funded by the Canadian Institutes of Health Research (CIHR) and the Heart and Stroke Foundation of Canada.
It was published in the peer-reviewed Journal of Alzheimer's Disease.
The media reported the story fairly accurately, but were overly optimistic that the results of such a small trial could soon be used to predict the onset of Alzheimer's disease. 

What kind of research was this?

This was a cohort study that followed a group of people with MCI and a group of healthy volunteers over a period of two years. MCI does not necessarily lead to dementia, and this study aimed to see if there were any factors that could predict which people with MCI would go on to develop the condition, in particular Alzheimer's disease.
Early diagnosis is important as the symptoms and signs of Alzheimer's disease may only become apparent many years after the condition has started. This could result in a lost opportunity to start drug treatment that could slow the progression of the condition. However, as this was a cohort study it can only show an association and cannot prove causality. 

What did the research involve?

Researchers took a group of 45 people with MCI and a control group of 20 healthy elderly people recruited from the community with no symptoms of MCI. Both groups were followed up yearly for two years.
MCI was diagnosed in a memory disorders clinic through medical and neurological assessment, as well as cognitive testing. The condition was indicated by:
  • cognitive memory complaint by the individual – the individual was aware they had memory problems
  • reduced performance on clinical tests assessing memory, language or attention compared with that expected to be seen in line with age and education
  • essentially normal ability to perform daily activities of living
  • no dementia, as indicated by being above diagnostic thresholds on cognitive testing
People were excluded from the study if they had:
  • alcohol dependence
  • a general anaesthetic in the previous six months
  • a history of a severe psychiatric disorder
  • traumatic brain injury
  • any other disease known to impair cognition
The study participants had further cognitive tests, including tests of word recall, working memory and planning abilities, as well as an MRI brain scan to look at:
  • hippocampal volume (part of the brain involved with memory)
  • cortical thickness (the outer layer of brain tissue)
  • white matter hyperintensity volume (seen in ageing and some neurological conditions)
The researchers first compared the results between the two groups. They then compared the results of people with MCI who either did or did not develop dementia within the two years of the study. Lastly, they worked out which combination of results had the highest ability to predict which people would develop dementia. 

What were the basic results?

Of the MCI group:
  • 18 progressed to dementia – 15 with probable Alzheimer's disease and 3 with probable mixed dementia of Alzheimer's and vascular dementia
  • 22 remained stable
  • 5 were lost to follow-up
There were no differences between the control group and the MCI group in terms of age, gender or educational level.
As would be expected, at the beginning of the study the MCI group had significantly poorer memory than the controls for:
  • immediate recall
  • immediate recognition
  • delayed free recall
  • word pair learning
The MCI group also had significantly lower scores than the control group for working memory and planning abilities. There were no differences seen between the groups for task switching.
In terms of the MRI scan results, the average cortex thickness was significantly thinner in the group who developed dementia. It was also thinner in specific areas, such as the right anterior cingulate gyrus, a region of the brain thought to be associated with rational thought and decision making.
The researchers found that the combination of immediate recall and immediate recognition scores and the thickness of the cortex in the right anterior cingulate gyrus was the most accurate for predicting development of Alzheimer's, with an overall accuracy of 87.5%.
Specificity was 90.9% – that is, 90.9% of people who will not go on to develop Alzheimer's will not have the combination of recall and recognition problems or thinning of the right anterior cingulate gyrus.
Sensitivity was 83.3%, meaning that 83.3% of people who will go on to develop Alzheimer's will have this combination of test findings. 

How did the researchers interpret the results?

The researchers concluded that their "findings suggest that detecting preclinical Alzheimer's disease is probably best accomplished by combining complementary information from targeted [brain] and cognitive classifiers, and highlight the importance of taking into account both structural and functional changes associated with the disease." 


The researchers suggest that Alzheimer's disease can be predicted with an accuracy of 87.5% when thinning of the cortex in the right anterior cingulated gyrus is seen on MRI, alongside test results suggesting problems with recall and recognition.
This research does not indicate a new "test", as MRI and psychological testing are standard procedures when investigating the signs and symptoms of dementia. What is novel in this approach is looking at a specific combination of results as a potential way of predicting which people with MCI may develop Alzheimer's disease.
While this form of testing would be beneficial to accurately predict the onset of Alzheimer's disease, this was a small study that only followed people over the course of two years. Some forms of dementia can take years to develop. The results of the study would need to be replicated in a much bigger sample size before the technique could be used in clinical practice. 
Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on Twitter.

Links To The Headlines

Links To Science

Peters F, Villeneuve S, Belleville S, et al. Predicting Progression to Dementia in Elderly Subjects with Mild Cognitive Impairment Using Both Cognitive and Neuroimaging Predictors. Journal of Alzheimer's Disease. Published online August 20 2013

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