Disease Modifying Therapies – Clinician Information

Disease-modifying therapies (DMTs) for Alzheimer’s disease are treatments designed to alter the underlying biological processes of the disease, rather than providing symptomatic relief alone. Unlike traditional therapies such as cholinesterase inhibitors or memantine, which may temporarily improve cognition or function, DMTs aim to slow disease progression by targeting pathological mechanisms associated with Alzheimer’s disease.

The first approved DMTs for Alzheimer’s disease in Australia are anti-amyloid monoclonal antibodies, including donanemab and lecanemab. These therapies are designed to bind to and facilitate clearance of amyloid-beta plaques in the brain, a hallmark pathological feature of Alzheimer’s disease.

Clinical trials have demonstrated modest but statistically significant slowing of cognitive and functional decline in selected patients with early symptomatic Alzheimer’s disease, including mild cognitive impairment (MCI) due to Alzheimer’s disease and mild dementia stages. Treatment benefit appears greatest when therapies are initiated early in the disease course.

Patient selection and eligibility

Current DMTs are indicated only for carefully selected patients with:

• early symptomatic Alzheimer’s disease,
• confirmed amyloid pathology,
• genetic test confirming that they are APOE ε4 noncarriers or heterozygotes,
• and/or appropriate clinical and imaging assessment.

Diagnostic confirmation typically requires:

• amyloid PET imaging and/or
• validated cerebrospinal fluid or blood-based biomarkers.

Baseline MRI assessment is also required to evaluate for exclusionary cerebrovascular pathology and establish suitability for treatment.

Safety considerations

A key safety consideration with anti-amyloid therapies is amyloid-related imaging abnormalities (ARIA), which may include:

• ARIA-E (vasogenic oedema/effusions),
• ARIA-H (microhaemorrhages and superficial siderosis).

Most ARIA events are asymptomatic, although some patients may experience headache, confusion, visual symptoms, dizziness or, rarely, serious neurological complications.

Risk is increased in APOE ε4 carriers, particularly homozygotes, and careful counselling and monitoring are essential. APOE ε4 homozygotes are excluded under the current TGA indication for both lecanemab and donanemab.

Monitoring requirements

Treatment protocols typically require:

• regular MRI monitoring,
• infusion-based administration,
• specialist oversight,
• and multidisciplinary coordination.

Clinicians should ensure patients and families understand:

• expected benefits,
• limitations of therapy,
• potential adverse effects,
• and the need for ongoing monitoring.

Implementation considerations in Australia

The introduction of DMTs has significant implications for:

• memory clinics,
• diagnostic pathways,
• imaging capacity,
• workforce training,
• and equitable access across metropolitan and regional settings.

Access pathways, PBS reimbursement and long-term service delivery models continue to evolve within the Australian healthcare system.

ADNeT Registry

The Australian Dementia Network Registry is a clinical quality registry that has been established by
Monash University School of Public Health and Preventive Medicine, as part of the broader ADNeT initiative.

The primary aim of the ADNeT Registry is to collect and analyse real-world data from clinicians to monitor and enhance the quality of care and patient outcomes for people diagnosed with either dementia or mild cognitive impairment (MCI) in
Australia. The secondary aim of the ADNeT Registry is to facilitate the recruitment of participants into research,
and to establish a publicly available resource to assist further study into the risk factors for, and trajectory of,
dementia and MCI in Australia.

Any private or public clinic where dementia and mild cognitive impairment (MCI) are diagnosed may join the ADNeT Registry.

The Registry is well positioned to monitor the prescription of monoclonal antibody therapies (mAbs) in clinics across Australia. The mAbs module has been developed to collect data specifically on the safety and effectiveness of anti-amyloid monoclonal antibody therapies prescribed to people with MCI and mild dementia due to Alzheimer’s disease.

Find out more about the ADNeT Registry here.

Clinician Information- mAbs Module

Clinicians interested in the mAbs module have the option of participating in the Registry and the mAbs module or the mAbs module alone. This is free of cost with ethics and governance support, induction training and the ability to claim CPD points for participation. Participating clinics will also receive a bi-annual individualised benchmarked site report.

Please view the flyer below for an oversight of the mAbs module.

Community of Practice

ADNeT hosts a Community of Practice for clinicians prescribing and treating patients with new disease modifying therapies.

For further information – including how to join regular meetings and education sessions – please email adnet.cop@monash.edu