7. Genetic testing
Genetic testing and counselling
If you have a relative with a form of dementia and you are worried about inheriting the condition, you should speak to your GP.
Most people with the more common types of dementia will be reassured to know that the pattern of dementia in their family is down to chance, risk genes, medical factors or shared lifestyles.
With dementia becoming more widely diagnosed, 1 in 4 people aged over 55 now has a close birth relative with the condition. However, when all dementia is looked at, the fraction that is inherited as a simple single-gene mutation is very small.
Routine testing (that is, not just for research purposes) is currently available on the NHS for mutations in several genes that cause dementia. They are the Huntington's disease gene (HTT), the three familial Alzheimer's disease genes (APP, PSEN-1, PSEN-2), and several frontotemporal dementia genes (including MAPT, GRN and C9ORF72). As explained below, these tests are only offered in very specific circumstances and with proper counselling.
Routine testing for risk genes like APOE is not available on the NHS and is not generally recommended.
Testing for single-gene mutations
There are two different kinds of testing for the single-gene mutations that cause dementia: diagnostic genetic testing and predictive genetic testing. Both require a simple blood sample to be taken for testing.
Diagnostic genetic testing
If you have already been diagnosed with dementia, it may benefit you to know if this has been caused by a mutation. For example, it may confirm a diagnosis which affects your drug treatment, or it might make you eligible for a clinical trial.
Testing someone who already has dementia is called 'diagnostic' genetic testing. It is not common and is generally only recommended if the dementia shows a very strong pattern of family inheritance.
Knowing the family inheritance pattern means taking a complete medical history across three generations, if possible. This will look for diagnosed dementia, mental illnesses (eg hallucinations, delusions) and neurological conditions (eg Parkinson's disease, motor neurone disease) in the family. This should include the age when symptoms started, the age at death, medical records and any post-mortem findings. Unless this history suggests a very strong dementia inheritance pattern, it is unlikely that diagnostic genetic testing will find a mutation.
The person being tested will be offered counselling - as far as their dementia allows - before any diagnostic gene test. A supportive family member will also be counselled because a positive test result has implications for them and the person's relatives. Other family members may or may not wish to know the result.
Note that, even with a very strong dementia inheritance pattern, a negative genetic test is still quite common, particularly in FTD. This doesn't necessarily rule out the possibility of a genetic explanation for the dementia. It may be that the dementia is caused by a mutation that is not yet known, which can leave families living with uncertainty. Occasionally, a diagnostic genetic test will identify a genetic change which is not a clear mutation. Again, this can leave families living with a degree of uncertainty.
Predictive genetic testing
It is natural for healthy relatives of someone with dementia to be concerned that they are at risk. This is especially likely if a close relative is known to be carrying a mutation, or if there is a very strong pattern of dementia running in the family.
Genetic testing of people who are not affected by dementia to see if they carry a mutation is called 'predictive' genetic testing. This is because finding a mutation usually predicts with near-certainty that an individual will go on to develop that type of dementia, if they live long enough. Predictive testing will only be done when a mutation has already been found in the family, for example by diagnostic testing.
There are several reasons why you might choose predictive genetic testing. Firstly, it may remove uncertainty and allow you to plan for the future. Secondly, a positive result may make you eligible for a trial of a new drug. Thirdly, it may open up opportunities if you are planning a family (see 'Genetic testing in family planning' below).
However, predictive testing can be a very stressful process. The decision about whether or not to have testing is a difficult and personal one. There are no right or wrong choices, but it is important that you think carefully about being tested and make an informed choice.
If you do decide to be tested, you may have to live with the anxiety of wondering what the result might be, or deal with an inconclusive result. If you are found to have the mutation, this knowledge cannot then be unlearned. There are currently no treatments available that can prevent or slow the progression of the disease for those with a genetic form of dementia. A positive result also won't tell you when symptoms might start. This is why predictive testing is only done with expert genetic counselling - both before and after testing - over several months.
The result of the test will usually affect other family members too, some of whom might not want to know the outcome.
After counselling, most people who have a 50 per cent chance (such as children of the person with the mutation) actually choose not to go ahead with predictive testing. This may be because not knowing leaves room for hope, whereas the knowledge of a positive test result cannot be reversed.
It is worth noting that a positive predictive gene test cannot be used to discriminate against someone when it comes to buying property, getting insurance or planning financially for their future. This is because there is a moratorium (delay or suspension) on the use of predictive genetic test results agreed by UK insurance companies until at least 2019. This means that, other than in exceptional cases, the companies cannot use the results of predictive genetic tests or require anyone to take a genetic test before taking out insurance.
You will still need to tell the company if asked, as would anyone, about your family history and any diagnostic test results (testing of people who already have a diagnosis). You can also volunteer a predictive test result which is in your favour, if you choose to.
Genetic testing in family planning
Being able to test for the genetic mutations that cause familial dementia has now made genetic testing as part of family planning possible. This is an option when one prospective parent is known to carry a single-gene mutation, or is at risk because their parent had a mutation. In these circumstances, genetic testing of the embryo allows the parents to have a child who does not carry the mutation. The technique used is called 'pre-implantation genetic diagnosis' (PGD). It is a modified form of in vitro fertilisation in which DNA from very early embryos is tested for a mutation in the lab. Only embryos which do not have the mutation are put back into the mother's womb.
If successful, PGD means that the baby is almost certain not to have the mutation or to grow up to develop the particular kind of dementia.
It is possible in some centres to use this technology without the at-risk parent themselves knowing if they have inherited the mutation, if they choose not to.
PGD has been used for several years to help couples with Huntington's disease who are starting a family. It has also recently become available on the NHS for families affected by familial Alzheimer's disease or genetic FTD. As with predictive genetic testing, families considering PGD are offered extensive genetic counselling.
Testing for risk variants
No test for risk genes like APOE is offered within the NHS, other than in approved research studies. Predictive testing for variants like this provides none of the near-certainty that a positive test for a single-gene mutation offers. Even if you test positive for one or even two copies of APOE e4, you are still not certain to develop Alzheimer's disease. Likewise, even if you have no APOE e4 variants, you are not certain to remain free from the disease.
In spite of this, tests for APOE variants are available commercially in the UK by sending off a sample of saliva in the post. This is called 'direct-to-consumer' genetic testing because it is arranged over the internet without a doctor or counsellor being involved.
Direct-to-consumer genetic testing is controversial and testing for variants like APOE is not recommended by most specialists. This is partly because - as explained above - the results are not that informative. It is also because the private companies that sell the tests do not do enough to help the person interpret their own test results properly.