This page is a resource for general practitioners, neurologists, neuropsychiatrists, geriatricians, and other dementia specialists about using genomic testing for dementia care in Victoria.
We know that information on genomics in dementia care can be hard to find. We answer some of the common questions (including questions about the APOE gene and polygenic Alzheimer disease) and share some useful resources. Bookmark this page to keep it handy.
Please note: This information is not intended to replace personalised patient advice from a genetics expert.
- How is genomics and genetics used in dementia care?
- What types of dementia is genomics most useful for?
- What should general practitioners consider in dementia care?
- What genes are known to be associated with Alzheimer disease?
- What is the APOE gene and how does it affect dementia?
- What DNA tests are available for dementia?
- When should I consider genomic testing for my patient?
- How do I conduct a cognitive assessment?
- How can I support family members? Do they need genetic testing?
- What does the patient’s care pathway look like?
- What do I need to discuss with my patient?
- How do I order a genomic test in Victoria?
- How much will testing cost for the patient?
- Where can I find more resources?
How is genomics and genetics used in dementia care?
Genomic testing has several potential benefits for patients with symptoms of dementia. It is most useful for patients with early-onset (<65 years) and/or a family history of dementia.
In early-onset dementia, genomics can be used to:
- Confirm a dementia diagnosis and/or eliminate other conditions
- Identify a precise diagnosis after other ancillary investigations
- Provide a precise diagnosis using a simple blood or saliva sample for patients who may struggle to undergo other investigations due to cognitive difficulties
- Provide information for family members
- Form a unique treatment plan which is more accurate for the exact type of dementia
In late-onset dementia (>65 years), genetic testing is not very useful but can be considered for certain patients, such as those with a strong family history of a specific type of dementia. Genetic testing for late-onset dementia may be useful for rarer types of dementia, such as those secondary to vascular and metabolic disorders.
In some instances, genetic testing can also be used in unaffected people to understand an individual’s risk of developing dementia in the future. This can include:
- Testing biological relatives of those with an identified genetic dementia, to predict their own risk of developing dementia
- Enabling at-risk relatives to take early interventions, such as lifestyle changes to reduce their risk, delay the onset or lessen the symptoms of dementia
- Enabling patients and their families to make informed decisions about family planning
What types of dementia is genomics most useful for?
There are several conditions that are known to have genes associated with them. Known and newly discovered genes are recorded in databases and tools like PanelApp that provide a searchable catalogue of gene panel information including phenotype information, mode of inheritance and associated publications. Please note these databases may not be up to date and may list genes that may not be relevant to your patient.
Dementia genes are associated with conditions such as:
- Fronto-temporal dementia
- Early-onset Alzheimer disease (especially <60 years)
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
- Dementia associated with Creutzfeldt-Jakob disease
- Dementia associated with Huntington disease
- Dementia associated with leukodystrophies
- Some other types of neurodegenerative dementias (especially <65 years)
Is genetic testing used in late-onset dementia care?
A patient with younger onset dementia (<65 years) is more likely to have a single gene cause identified compared to those with late-onset dementia (>65 years). A significant majority of patients with late-onset dementia will have no identifiable single gene cause for their dementia. Late-onset dementia tends to be a combination of many small genetic changes that, together, can lead to a higher probability of developing dementia. This combined risk is known as a polygenic risk score. Currently, polygenic risk scores are not used in clinical diagnosis or care for dementia.
For patients with late-onset dementia and a strong family history of a specific type of dementia, genetic testing may be considered. For patients with late-onset dementia without a strong family history, genetic testing is not recommended.
Targeted genetic testing may be used to determine a patient’s suitability for certain therapies, such as testing for the APOE genotype to assess risks associated with emerging anti-amyloid therapies.
What should general practitioners consider in dementia care?
If you are a GP, you can consider referring to a dementia specialist for diagnosis. Formal tests and / or imaging results showing cognitive change, memory impairment or dementia is usually required before genetic testing is introduced. Genetics services are happy to assist GPs with any questions. You can contact your relevant genetics services using this finder. Dementia Australia is also an excellent source of information and support for people living with dementia and their family members.
To support patients with dementia symptoms, general practitioners can:
- Be aware of the risk factors of dementia
- Know when to refer to a neurologist or other appropriate specialist
- Record a comprehensive family history
- Offer specialist referral for patients with strong family history and/or possible symptoms of dementia
- Access resources and support services for ongoing dementia care
- If genetic dementia is suspected, refer patients and their families to a clinical genetics service
- Offer to include a patient’s family members in conversations early, identifying their concerns and needs
- Provide psychological resources and supports to patients and their families
This resource from Dementia Australia can help health professionals assess and diagnose dementia.
Which genes are known to be associated with Alzheimer disease?
There are three genes known to be associated with early-onset Alzheimer disease, they are APP, PSEN1, and PSEN2. Specific DNA changes within these genes will determine the early onset of Alzheimer disease.
There are also ‘risk factor’ genes that contribute to an individual’s risk of developing Alzheimer disease, the most recognised being the APOE gene.
What is the APOE genotype and how does it influence the risk of Alzheimer disease?
The most important known genetic factor affecting an individual’s risk of developing Alzheimer disease is called Apolipoprotein E (APOE). Located on Chromosome 19, every person has two copies of the APOE gene, one copy inherited from each parent.
The APOE gene variants has three clinically important forms, also known as genotypes:
- APOE-ε2
- APOE-ε3
- APOE-ε4
A person can inherit different combinations of APOE. You can have two of the same or two different variations of the APOE genotype.
People with the APOE-ε2 genotype, especially those with two copies of this variation, appear to be protected against developing Alzheimer disease. However, this does not mean an individual is immune to developing dementia.
The APOE-ε4 genotype increases a person’s risk of developing late-onset Alzheimer disease. Having at least one copy of APOE-ε4 puts patients at an increased risk of developing Alzheimer disease. Having two copies of APOE-ε4 puts patients at a much higher risk of developing Alzheimer disease.
However, not everyone with the APOE-ε4 genotype will develop dementia. The onset of dementia is also dependent on an individual's environmental, lifestyle and social factors. Many individuals with two copies of APOE-ε4 may never develop dementia.
The graphic below describes the factors, including the APOE-ε4 genotype , that contribute to a person’s risk of developing dementia.
Legend
1
- Having one copy of APOE-ε4 increases an individual’s risk of Alzheimer disease
- Having two copies of APOE-ε4 further increases an individual’s risk of Alzheimer disease, but there is no certainty of developing the condition
2
- Every person is born with other genetic susceptibility and protective factors
- Different people have different genetic factors
- These can contribute to an individual’s overall likelihood of developing Alzheimer disease
3
- Individuals also acquire environmental and lifestyle factors that contribute to overall risk of developing Alzheimer disease throughout life and aging
- When an individual accumulates enough genetic, environmental, lifestyle, and aging factors, they may reach a threshold for developing Alzheimer disease
Model adapted from Cook BC, Slomp C and Austin J. (2022). DOI:10.1007/s12687-021-00558-9
You can read more about Alzheimer disease genetic risk factors.
What DNA tests are available for dementia?
There are several genetic tests that can be used for patients presenting with dementia symptoms. These include:
- Single gene tests, whichlook for genetic changes in one gene. Where there is a high clinical likelihood, this could be done to confirm or rule out a specific genetic cause.
- Targeted panels, which look at specific groups of genes.
- Whole exome sequencing, which sequences and analyses the protein-coding regions of the genome. These are the areas most likely to impact the protein expression.
- Whole genome sequencing, which sequences the entire genome, including the non-coding regions, and analyses the areas suspected to be a cause of the condition.
It’s important to note that genomic testing is complex, and there are a number of factors to consider.
- Genomic testing can benefit from expert clinical genetics input. Reach out to your local genetics service for support or advice.
- Unexpected and uncertain findings are common for this type of testing. Unexpected or incidental findings occur when a genetic change that doesn’t explain the patient’s condition is found but relates to other possible health conditions. An uncertain finding, also known as a variant of uncertain significance, occur when the impact of a variant on the function of the gene is unknown.
- As of August 2024, genomic testing for dementia is not currently funded by Medicare. However, some neurology departments and genetics services will fund the test for patients where it is clinically appropriate.
When should I consider genomic testing for my patient?
The following referral criteria diagram can help you determine if genomic testing is right for your patient.
How do I conduct a cognitive assessment?
Dementia Australia has a guide on the assessment and diagnosis of dementia. GPs can refer to the general practitioner assessment of cognition.
Alternatively, you can refer someone in your care to Dementia Australia. They can connect patients with appropriate supports. Family members can also make personal referrals through this service.
How can I support family members? Do they need genetic testing?
Family members may be concerned about their own risk of developing dementia later in life. They may also choose not to know their genetic risk. Any asymptomatic person should be referred to a genetic counsellor to make sure they fully understand the implications of genomic testing. There are options for referral within the public and private health care settings.
Resources for patients and families
- Support groups and websites are available for genetic conditions – a genetic counsellor can help link your patients with further support
- Ensure families know what to expect and where to go for help. You can point them to the Dementia guide for patients and families.
Genetic counsellors are expert genomic communicators.
They can explain genetic conditions to individuals and families and provide one-on-one emotional and practical support to help people adjust to living with, or being at risk for, a genetic condition.
Some people may not want genetic testing, and genetic counsellors are best placed to talk through all the considerations of testing. You can refer your patient to a genetic counsellor by searching for your local Genetics Clinic Service Finder.
What does the patient’s care pathway look like?
Patients often go through multiple clinical investigations before a dementia diagnosis is confirmed. Genomic testing can help speed up the process. The patient pathway diagram below provides an overview of some of the healthcare professionals involved in making a dementia diagnosis and the clinical investigations they may take.
What do I need to discuss with my patient?
Informed consent
Pre-test counselling is important to ensure the patient and/or their family members understand the implications of genetic or genomic testing. Written consent is needed, by the patient or their medical decision-maker.
Australian Genomics has developed standardised consent forms for genetic and genomic testing, along with resources for health professionals seeking informed consent. Genetics services can often provide support with the consenting process.
Genetic testing of asymptomatic family members requires informed consent and pre-test appointments with a genetic counsellor.
Considerations specific to genomics and genetics
Due to the unique features of genomic and genetic testing, it’s important to discuss all of considerations with patients. For example:
- How would the patient feel about the possibility of being diagnosed with an irreversible condition?
- Would they still want to know about a condition with only limited treatment options available?
- What are the implications for their family members? Do they have similar symptoms and need testing? What supports do they need?
- Is this the right time for the patient to get genomic testing done?
- How will it affect their employment?
- Will this affect their family planning decisions?
- Do they have concerns about genetic testing or insurance?
How do I order a genomic test in Victoria?
The RACGP has clinical guidelines for ordering genetic or genomic tests, including testing for Alzheimer disease and other neurological conditions. Some can be ordered by specialists; others can be ordered by genetic counsellors.
If you are ready to order a genomic test, you can contact a NATA-accredited pathology laboratory. However, interpreting genetic test results can be a complex process. You may wish to contact a genetics service instead.
How much will testing cost for patients?
Genomic or genetic tests can range from $400 to $5000 depending on the test type. Some tests may be provided at no cost to the patient at some hospitals and genetics services. The Genetics Clinic Service Finder can help you find your patient’s local genetics service.
As of June 2024, Medicare funded genetic or genomic tests are not yet available for dementia. However, some patients with concurrent conditions (such as motor neuron disease or mitochondrial disorders) may be able to receive Medicare-funded genetic testing.
Where can I find support and resources?
- You may wish to reach out to a genetic counsellor or clinical geneticist who specialises in neurogenetics, or to your local genetics clinic. You can find your closest service by using the Genetics Clinic Service Finder.
- Dementia Australia has a comprehensive list of information for health professionals including professional development and training. You can also find a range of patient support resources.
- You can find resources to assist dementia patients with financial issues, employability, legal issues, driving, accessing services and more at the Eastern Cognitive Disorders Clinic.
- GeneEQUAL have a series of easy-read booklets about genetics designed for patients with low literacy levels.