0 hours
These are activities that expand general practice knowledge, skills and attitudes, related to your scope of practice.
0.5 hours
These are activities that require reflection on feedback about your work.
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These are activities that use your work data to ensure quality results.
These are activities that expand general practice knowledge, skills and attitudes, related to your scope of practice.
These are activities that require reflection on feedback about your work.
These are activities that use your work data to ensure quality results.
Australians can finally get disease-modifying drugs for Alzheimer’s disease, but many GPs are in the dark on how to best help patients get assessed and manage those receiving treatment.
Of 1000 GPs recently surveyed by Healthed, around half said they were not at all confident in monitoring and supervising patients who were taking the infusions, and only one in four was moderately or very confident.
Yet interest is growing after the TGA approved donanemab (Kinsula) in May and lecanemab (Leqembi) in September. One in five GPs said they saw at least one patient in the previous fortnight who was seeking more information on these monoclonal antibodies.
In light of this, experts say now is the time for GPs to make connections with local specialist services and boost their knowledge of the drugs.
While GPs generally said they felt confident using cognitive assessment tools and supporting patients with new diagnoses, only one in three were at least moderately confident referring them for assessment for monoclonal antibody therapy.
Yet the drugs are indicated only in the early stages of Alzheimer’s disease, and those in the earliest of early stages stand to benefit the most, said Associate Professor Steve Macfarlane, head of clinical services for Dementia Support Australia.
So a speedy diagnosis is key.
“People will have symptoms, on average, for about three years before they get a diagnosis,” the Associate Professor of Aged Psychiatry at Monash University said.
“That is potentially time lost as far as the patient’s likelihood to benefit from the drug is concerned.”
Associate Professor Macfarlane said that while historically there was less urgency when referring patients due to the lack of disease-modifying treatments, “That has changed now”.
To get the treatment, patients with mild cognitive impairment or mild dementia also need confirmed amyloid plaques – the hallmark of Alzheimer’s disease.
Confirmation has typically required PET imaging or CSF biomarkers, but the development of several new blood biomarkers look set to expand GPs role triaging potential patients.
The first of these, Roche’s pTau 181 plasma test, was approved in October for use in general practice to rule out amyloid pathology in patients aged 55-80 years who have subjective cognitive impairment or decline, or suspected mild cognitive impairment.
The pTau 181 test is very good at identifying people who don’t have amyloid plaques but it’s only around 50% accurate at identifying people who do have them.
Patients who aren’t ruled out need to see a specialist to discuss further diagnostic testing, including any amyloid PET or CSF study, to determine if they have the disease, Associate Professor Michael Woodward, director of dementia research at Austin Health said.
However other blood tests are on the horizon.
“Within the next 18 months in Australia, we’ll probably have a simple blood test available for general practice, which will be able to demonstrate amyloid proteins in the blood and have a similar sensitivity and specificity to amyloid PET scanning,” Associate Professor Macfarlane said.
PET scans are expensive and hard to get at the moment, said Associate Professor Macfarlane, who also works in private practice as an old age psychiatrist.
“So a simple blood test, possibly costing a couple of hundred dollars, would make accurate and timely diagnosis much easier within the general practice setting.”
Patients also need a baseline MRI to determine their suitability, which GPs could do and send to the specialist.
Because of this and the need for three-monthly MRI safety monitoring, patients with MRI contraindications such as metal implants like pacemakers are generally ineligible for monoclonal antibody therapy.
The downside is that MRIs ordered by GPs are likely to cost the patient several hundred dollars out of pocket, whereas they may be free when requested by the specialist. But given the overall expense of the drug, that additional cost may not be a barrier in this cohort, Associate Professor Macfarlane said.
“An MRI being sent to the specialist, along with the referral and the APOE genotype would streamline the process significantly.”
Gene testing is needed to check APOE4 carrier status, which informs risk of amyloid related imaging abnormalities (ARIA) such as brain swelling and microhaemorrhage. The medicines are not indicated for patients with two copies of the APOE4 genotype (homozygotes) due to increased risk of developing ARIA compared with non-carriers and compared with those who only carry one copy of the APOE4 genotype (heterozygotes). Risk of developing ARIA is lowest in non-carriers.
However, GP Steph Daly, founder of Sensus Cognition, a GP-led memory clinic based in Adelaide cautioned that genetic testing without adequate genetic counselling skills may not be appropriate for all GPs. It may be something GPs do more in the future, but for now GPs could simply advise patients these tests will be part of the assessment, she said.
And there are other ways GPs may be able to streamline the referral process.
Associate Professor Woodward said tests for thyroid disease, B12 deficiency, folate deficiency and syphilis serology were a necessary first step for treatment that GPs could easily do. These conditions are not commonly mistaken for Alzheimer’s disease, but they need to be excluded as possible causes of cognitive impairment, he said.
Ultimately, only 10-20% of people with Alzheimer’s disease, either in the mild dementia or mild cognitive impairment stage, are eligible for these medicines. Exclusions include moderate or severe dementia, significant co-pathology, inability to tolerate regular infusions and high bleeding risk.
However, patients who can safely stop anticoagulants may be eligible, Dr Daly said.
One important role for GPs is in explaining that these are not cures, and patients will ultimately still decline over time.
Clinical trials suggest the drugs may slow the progression of cognitive decline by around 25-35%, with patients who start at an earlier stage of illness getting the most benefit.
Dr Daly recommends framing the benefit in terms of time rather than percentages, which can feel more abstract.
She tells patients that at the end of the 18-month study period, researchers found patients on the medications had “gained around six months maintaining the same state they were in, compared with other people who weren’t on the drug and declined further.”
Associate Professor Woodward said projected data suggests that it takes around four years from the start of treatment before those who received the drugs decline to the same degree as those who had placebo.
Costs are one of the major barriers. The medicines are not covered by the PBS, and cost around $45,000 per year, or around $60,000 per year when you add in scans, monitoring and specialists’ fees (with treatment typically lasting 18 months).
The high cost of the drugs and the potentially large number of eligible patients mean PBS listing is unlikely in the next five years, Associate Professor Macfarlane said. If they do get covered, it will likely only be for the group of patients that closely match the clinical trial cohort, he added.
Private health insurance may cover some costs, especially of scans, and DVA will pay for drugs and other expenses for eligible patients.
Patients can also enter clinical trials as a possible alternative pathway to access drugs for free.
Regardless, Dr Daly said patients should be given all the information to make their own decisions, rather than doctors assuming what they and their loved ones are willing to pay. While the ticket price may seem high, she noted costs were comparable to other expensive drugs such as cancer immunotherapies – and the extension of life may be similar.
Most monitoring is managed by specialists and infusion clinics, but there are some crucial things GPs need to be aware of.
ARIA, or amyloid-related imaging abnormalities, are the main side effects and can include microhaemorrhages and swelling of the brain.
Most ARIA are asymptomatic, and are picked up by routine MRI monitoring – every three months or more – by the specialist overseeing the infusion, Associate Professor Woodward said.
However, ARIA can sometimes present as similar to a stroke, both in terms of neurological symptoms such as headache, blurred vision and dizziness, as well as on imaging that might be done when the patient presents to the emergency department, the experts all emphasised.
This can be problematic if the patient is then given thrombolytics – which can be fatal for someone on these drugs.
“If a patient presents to you with neurological or even vaguely neurological symptoms, such as headache, it would be good to either contact the specialist overseeing the infusion of the monoclonal antibodies, or alternatively, arrange for the patient to go to the emergency department,” Associate Professor Woodward said.
“The big trap here is that sometimes the symptoms can mimic a stroke and when the brain imaging is done in the emergency department, ARIA can, on some occasions, look like a stroke,” he warned, adding that for these patients, thrombolytics “can lead to massive haemorrhaging and patient death – and that has occurred on some occasions.”
Associate Professor Macfarlane said ARIA should be flagged with any referral letter that GPs might make to an emergency department for evaluation.
Patients can also carry alert cards or medication bracelets to warn of potential side effects, Dr Daly said.
Infusion clinics monitor for infusion side effects, but in some cases these develop after the patient leaves the clinic.
Anaphylaxis was almost never seen in the trials, Associate Professor Woodward said. But fever, flushing, myalgia, hypotension, headache and malaise are more common – and may occur up to 24-48 hours after infusion.
Severe symptoms warrant a call to the infusion clinic, but with mild symptoms patients can be reassured and advised to speak to the specialist at the next most convenient time, he said.
Associate Professor Woodward said that regardless of a patient’s eligibility for the drugs, advice and support on slowing cognitive decline is crucial.
“We do what we should have been doing for the last 120 years, which is basically talking to them about brain health, which is improved by exercise, diet, social activity, mental activity, etc.”
In addition, GPs can help patients and their families with advanced care planning, and direct them to valuable services such as Dementia Australia and Forward With Dementia.
“We need to make sure that their support services are in place, that they’ve had an aged care assessment if needed and got an appropriate support package, because that takes up to a year to activate,” he said.
Given half a million Australians have dementia and another million have mild cognitive impairment, it can be comforting for patients to know they are not alone, Associate Professor Woodward said. “Many will go to the grave with Alzheimer’s – not because of it.”
“The truth is, there’s a lot of people with Alzheimer’s, and there’s still life with Alzheimer’s.”
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