ApoE4 test offers ‘false worry, false comfort’

5 minute read

GPs facing requests for Alzheimer’s gene testing after Chris Hemsworth’s revelation can assure patients they don’t need it.

Testing for the ApoE4 gene mutation linked to Alzheimer’s is not helpful, particularly accurate or predictive for individuals, experts say.

A spate of inquiries about the genomic test is expected after screen icon Chris Hemsworth revealed he was tested and has two copies of the mutation, giving him an increased risk of developing the disease. Experts say there are solid reasons why patients should be counselled against it.

“It is not a good test,” said Austin Health Associate Professor Michael Woodward, and it has the potential to both “falsely worry” and “falsely reassure.”

“The biggest risk factors for Alzheimer’s are having a family history and age, not E4. So it makes little sense to have a test that’s just going to suggest you’re high risk because you know you’re high risk anyway from the family history, without even knowing about the gene,” said the Dementia Australia honorary medical advisor.

Furthermore, many people with the mutation never develop Alzheimer’s and 40% of people with Alzheimer’s do not have the gene, he explained.

“So if you have a negative test you might wander away feeling falsely reassured – well, I’m never going to get Alzheimer’s – so you go and hit the pub for food and drink too many bottles of wine and you’re not being attentive enough to your own risk factors.”

Hemsworth, the 39-year-old Australian actor famous globally for playing Thor in the Marvel movie franchise, took the genetic test as part of a documentary series into longevity. He told fashion magazine Vanity Fair that he had decided to reveal the results as a “motivator for people to take better care of themselves and also understand that there are steps you can take”.

About 2-3% of people have two copies of the mutation, putting them at up to nine times the risk of developing late onset Alzheimer’s disease. According to data published in the Canadian Medical Association Journal in 2018, the absolute 10-year risk for those women and men, respectively, are 7% and 6% at age 60-69, 16% and 12% at age 70-79 years, and 24% and 19% at age 80 and older. The gene is also associated with earlier onset of the disease.

But professor of primary care cancer research at the University of Melbourne Jon Emery said the genomic test for ApoE4 is not particularly accurate or predictive

“The ApoE4 just doesn’t give you that level of precision. It’s not like the BRCA test where you can provide absolute risk estimates as to their likelihood of developing breast and ovarian cancer, and then you’re talking of risks of maybe up to 50%,” Professor Emery said.

“[ApoE4] is not strongly predictive of whether you will get Alzheimer’s or whether you won’t and there are limited options other than the lifestyle changes you would recommend to anybody.

“There are a number of other factors that affect the likelihood that you will actually develop it. Some of those are other genetic factors, some of it’s having a family history; but there are also modifiable factors as well, such as diet, exercise, whether you have cardiovascular disease. So it’s not a strongly predictive test,” he said.

In Australia, the test is not covered by Medicare and can cost several hundred dollars.

“It is offered by commercial companies, sometimes as part of very broad genomic panels of tests. The challenge is that you get quite lengthy, quite complex reports. And it tells you that you’re at a little increased risk of x and a little bit reduced risk of y. And some of those tests have less certain accuracy and certainly limited utility,” Professor Emery said.

Public health guidance, like that given in the shortly to be updated Genomics in General Practice, is generally that the test does not have “sufficient clinical utility”, Professor Emery said. “But at the same time, these tests are about individual choices; some people like to know about their risks. And for some people that has personal utility,” he noted.

They might be motivated by the knowledge to alter modifiable risks, he said. “But on the whole … there isn’t much evidence that providing just purely genetic risk information leads to people changing their lifestyle behaviours.”

Both Professor Woodward and Professor Emery said knowing you have the gene but have limited risk reduction and therapy options can cause decades of anxiety.

“If you feel your memory is declining, then you should certainly be assessed by a proper specialist, geriatrician, neurologist or a psychogeriatrician. But the worried well should just be counselled not to have the test,” Professor Woodward said.

“There’s no reason for having a gene test,” Professor Woodward said. “You should adjust your lifestyle now. You should exercise, eat a good diet, keep your brain active, socially interact. You should treat blood pressure and diabetes and cholesterol vigorously. You should wear hearing aids. These are all ways of reducing our risk of Alzheimer’s.”

End of content

No more pages to load

Log In Register ×