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A BLOOD TEST TO PREDICT ALZHEIMER’S DISEASE?

MD-FM Thursday March 13, 2014

 

SARAH:

MD-FM medical news from around the world.  Here’s Peter Goodwin:

 

SEGMENT 1: ALZHEIMER’S DISEASE: Blood test identifies patients at risk within three years

 

PETER:

Hello, and to begin with: it might become possible one day to detect your risk of developing Alzheimer’s disease by using a simple blood test. Here’s Sarah Maxwell:

 

SARAH:

Yes, in Nature Medicine, researchers report their discovery of the first blood-based test that can predict with greater than 90 per cent accuracy whether a healthy person will develop Alzheimer’s disease within three years. The team has identified ten blood lipids that can predict disease onset. The first author is Mark Mapstone:

 

MAPSTONE:

These ten lipids are critically important for maintaining the structural integrity of cell membranes. So, when you have cell death, you are going to see some of these membrane constituents present in abnormal concentrations. But we also have plans to look at transcripts, plans to look at proteins and DNA as well. So those analyses are forthcoming and we hope that they can flesh out the story a little bit more.

 

SARAH:

Dr. Mark Mapstone, from the University of Rochester, New York. And he told us the test needs further validation before it can be considered for use in practice. But it could be very useful for research:

 

MAPSTONE:

This tool can be used for screening for clinical trials. We think it’s important to be able to initiate disease-modifying therapies when the substrate is receptive: before the symptoms become manifest and the disease has gone too far that interventions don’t prove successful.

 

SARAH:

So far, most of the detection methods have relied on cerebral spinal fluid and neural imaging techniques. We asked neuro-epidemiologist Monique Breteler, who did not participate in the study, for a comment:

 

BRETELER:

If we are to develop a screening test for Alzheimer’s disease that can be used widely, then we need to have relatively simple, cheap tests. And of course there is no way that we can start screening entire populations by lumbar punctures or fancy imaging methods. And a blood-based test would make a major contribution to bringing screening for preclinical Alzheimer’s disease closer. This is where the field should move.

 

SARAH:

That was Professor Monique Breteler, from the German Center for Neurodegenerative Diseases in Bonn, Germany.



SEGMENT 2: Compression stockings are just as effective for treating venous leg ulcers as traditional four-layer bandages

 

PETER: 

Now for healing venous leg ulcers, two-layer compression stockings were just as effective as the standard, more bulky, four-layer bandages…

 

SARAH:

Yes, in The Lancet, patients with venous leg ulcers were randomized to one or the other of these two methods and followed-up for as long as a year. In both groups: the median healing time was around three months and 70 per cent of ulcers healed. Interestingly: ulcers recurred less often in the hosiery group: 14 per cent of patients had recurrences compared to 23 per cent in the group with bandages. Co-author Jo Dumville speculated for us on what could be happening: 

 

DUMVILLE:

We hypothesized that people in the trial who liked wearing compression hosiery kept on wearing it after they had healed, possibly also wearing it at higher compression levels than they might have done if they hadn’t received this treatment and so it helped to prevent recurrence of further episodes of ulceration.

 

SARAH:

Dr. Jo Dumville, lecturer in Applied Health Research at the University of Manchester in the UK. And she warned that the recurrence analysis only took place in people who healed –not within the randomization. So it needs to be interpreted with caution. Finally, however, stockings were also more cost-effective:

 

DUMVILLE:

The cost of treating people using two layer stockings was on average 300 pounds less in the stocking group. That difference in cost seems to be driven largely by the reduced number of nurse visits required for people who are using two-layer stockings… And they also had slightly higher quality-adjusted life-years.

 

SARAH:

Dr. Dumville did note, however, that some patients preferred wearing bandages… So stockings should not always replace bandages –both should be offered to patients.



SEGMENT 3: Wearing compression stockings does not prevent post-thrombotic syndrome

 

PETER:

However, another study in The Lancet reports that wearing compression stockings after a first episode of proximal deep vein thrombosis did not prevent the occurrence of post-thrombotic syndrome. In a trial, 800 patients were randomized to wearing either active or placebo stockings, for two years. Results were similar in both groups. So the authors conclude that the findings do not support routine wearing of compression stockings after an episode of DVT.



SEGMENT 4: Simple urine test can distinguish between different causes of kidney dysfunction after transplantation

 

PETER:  

Improving management of renal failure after kidney transplantation. In the Journal of the American Society of Nephrology, researchers suggest a simple urine test could one day replace invasive biopsies to help guide treatment for acute kidney graft dysfunction.

 

SARAH:

Yes, The team reported how the test they designed can distinguish between the main causes of raised creatinine in patients who’ve had renal transplants. It does this by measuring levels of certain messenger RNAs excreted in urine: namely ones that reflect either acute tubular necrosis or acute rejection, which currently need a biopsy to diagnose.

 

MATIGNON:

We measured in urine mRNA levels of 20 genes that are known to be involved and we identified a linear combination of six messenger RNA and we can distinguish acute rejection from acute tubular injury. It’s important because acute rejection patients do need rapid treatment and, right now, clinicians are very bad to predict the results of biopsies.

 

SARAH:

That was Dr. Marie-Benedicte Matignon, from Hôpital Henri Mondor in Creteil, France, who told us the test will need to be validated externally and tested in prospective studies. Professor Uwe Heemann, from Germany, who did not participate in the study, thought, however, we were still far from a reliable test:

 

HEEMANN:

There are a number of studies that go for mRNA in the urine and the problem is that every study finds a different correlation. In the future, there will be certainly a possibility to have mRNA profiles in the urine as replacement or addition to the results of the biopsy, but currently I think there’s a lot of work to do until we get so far.

 

SARAH:

That was Professor Uwe Heemann, head of Nephrology at the Technical University of Munich, in Germany.



SEGMENT 5: Exposure to traffic air pollution associated with morphological changes in right heart

 

PETER:

Pollution and heart disease now: for the first time in humans, exposure to high levels of air pollution from road traffic has been associated with anatomical changes in the heart’s right ventricle...

 

SARAH:

Yes an MRI study showed that higher levels of exposure to nitrogen dioxides were associated with a mean five per cent increase in right ventricular mass and a three per cent increase in right ventricular end-diastolic volume, which themselves are known to be associated with heart failure and death. Dr. Leary, first author of the study in the American Journal of Respiratory and Critical Care Medicine:

 

LEARY:

It’s kind of a population level change, which means that, for any individual participant, we wouldn’t be able to make very strong conclusions about these changes but, based on the power of this study to try and understand the mechanisms and underpinnings of diseases, we think that there is an association there, which may suggest a biologically relevant mechanism.

 

SARAH:

Dr. Peter Leary, from the University of Washington in Seattle, hypothesized on the mechanisms at play:

 

LEARY:

The pattern that we see looks like a right heart that is under increased pressure. And so my best guess is that inhaled air pollution is deposited at very high concentrations in the lungs and, more likely than not, leads to some level of vasoconstriction of the pulmonary vasculature. And that could occur through a variety of mechanisms. But it’s possible that, because inhaled air pollution is so inflammatory, the association that we see may be driven by direct effects of air pollution on the heart itself, as opposed to indirectly through the pulmonary vessels.

 

SARAH:

A few years ago an association had already been demonstrated between exposure to nitrogen dioxide and morphological changes in the left ventricle…

 

LEARY:

So I would say that this joins other studies in strongly supporting a case for decreasing environmental air pollution at the system level.

 

SARAH:

Peter Leary, from Seattle.



IN BRIEF 1: Whole genome sequencing not ready for widespread clinic use

 

PETER: Finally, in brief: New findings suggest there are still quite a few technical challenges to overcome before whole-genome sequencing can reliably be adopted as a tool for clinical practice. A study in JAMA has shown that although the technology increases the numbers of genetic variants detected per person, many of the variants you really need to know about –those with high clinical importance –were not covered. Also sequencing results were inconsistent between platforms; and often experts didn’t agree on which findings are most meaningful.

 

IN BRIEF 2: Molecular subtyping better than genetic testing to assess patients’ risks of breast cancer recurrence

 

PETER:

Molecular sub-typing was more accurate than genetic testing for identifying patients at high risk of breast cancer recurrence –these are the findings of a trial with 148 patients, presented in a poster session last weekend at the Miami Breast Cancer Conference in Florida. The implication is that molecular subtyping should be better to help identify patients who would benefit most from chemotherapy.


PETER:

That’s all from MD-FM for now.  Sarah Maxwell and I will be back with more next week, so until then, from me Peter Goodwin, Good-bye.

 

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