How did you become involved in Alzheimer’s disease (AD) research?

Growing up, I always had a sense that I would be involved in an important mission, but I wasn’t sure what it was. After medical school I completed residency training in neurology and psychiatry, and I wanted to make a difference against a major brain disease. I was drawn to the AD field because of the magnitude and urgency of the unmet medical need. As a child, I saw the impact that a long course of dementia had on my grandmother and my family and I’m sure that influenced my decision to devote my career to research on AD. Caring for my grandmother and other members of my family and my wife’s family with dementia has made me a better doctor. When families share their stories, I know how they feel.

Disease-modifying therapies (DMT’s), despite being a significant breakthrough in AD treatment, can’t cure dementia or stop it from happening. What are the best possible outcomes for patients who choose to undertake this treatment?

DMTs are approved for people with early AD, MCI and mild dementia, helping people remain at a milder stage of AD longer with greater independence and quality of life.

There is a lot of controversy around the validity of DMT’s working to improve or stabilise cognitive function. What are some of the most promising drugs available, or being developed, in your opinion, and have you seen them work firsthand?

Lecanemab, a monoclonal antibody, is the first fully approved treatment that lowers a key component of AD, the buildup of amyloid plaques. This medication is given intravenously every 2 weeks and is approved in the US, China, Japan and Korea. Donanemab, another monoclonal antibody that lowers amyloid, given IV monthly, is under review* and is likely to receive full FDA approval soon. These medications open a new molecular era for the diagnosis and treatment of AD.

This is a transformative time for patients with Alzheimer’s disease, where AD is increasingly viewed as a treatable condition and managed like other major chronic diseases such as heart disease and cancer. This will involve early diagnosis with molecular confirmation, disease modifying treatments started early, risk reduction and prevention strategies and much better coordination of care.

The amyloid-lowering antibodies are just the beginning. New treatments are being tested that target other proteins such as tau, that will likely eventually be given in combination with amyloid-lowering medications. Forty percent of the risk of AD is modifiable, largely through a healthy lifestyle and all of us should adopt habits early in life to keep our heart and brain healthy, such as controlling risk factors for heart disease, vigorous exercise, eating a Mediterranean-type diet and staying mentally stimulated and socially active.

From your experience in the US, what are the main challenges in implementing DMT’s in clinical use in Australia? You made a memorable statement in your keynote speech at ADRF – “We must always vow to put the welfare of our patients first”. How cautious should we be about amyloid-related imaging abnormalities (ARIA) occurring with these new therapies?

DMT’s require important changes to AD clinical care. Primary and specialty providers are needed to help identify patients with mild cognitive impairment and mild dementia. This requires treatment teams with access to infusion centers and amyloid testing with PET scans or spinal fluid. It is our responsibility to select appropriate candidates for treatment and to always put the welfare of the patient first.

To deliver these medications safely, dementia specialists, radiologists and emergency providers need to become familiar with the detection and management of ARIA. This requires careful review of the baseline MRI scan and regular MRI safety monitoring, testing for the ApoE gene and frank discussions with patients and families about the risks and benefits of treatment. Patients and families need to work closely with their providers to keep a mild side-effect from becoming more serious.

We are on the cusp of reliable new biomarkers for AD detection. How will these new tests impact the dementia landscape in the immediate future?

It is difficult to diagnose AD accurately, especially in primary care. Reliable blood tests are on the horizon to help improve the accuracy of diagnosis. This will soon help screen for AD pathology, which is required to be considered for amyloid-lowering treatment. These tests must be approved by regulators, such as the FDA/TGA, and covered by health insurers. I was surprised and dismayed to learn that there is often a long delay between approval by the Australian TGA and coverage by Medicare. In the US patients and families protested outside Medicare offices and advocates lobbied Congress and other government officials to ensure that Medicare covered the new medication on day 1 and it worked.

You mentioned your wife is a nurse and emphasised the role nurse practitioners play in managing the administration and follow-up care in patients taking DMT’s in the US. How much of an impact does this have on clinicians’ workload?

The coming advances in diagnosis and treatment will require important changes to care models for AD. It will not be possible to provide high quality dementia care in a new molecular era to already overburdened practice settings without providing additional resources and staffing. To optimize quality of life, patients and families will require management from experienced care navigators throughout the disease course beginning at the time of diagnosis. This will require adding nurses, nurse practitioners and care navigators trained in dementia care to primary care and specialty practices.

My wife, Diane, and daughter, Rachel, are both amazing advanced practice nurses and I know the healing and transformative power nurses can have. Diane has actually helped pioneer many of the advances in AD care presented at the ADRF and it has been very rewarding sharing this mission and career journey with Diane.

You are an incredibly respected expert in your field with many years of experience in AD research and we thank you for sharing your knowledge at ADRF2024. Was there anything you learned from the conference, despite your vast experience?

The Australian Dementia Research Forum is a great meeting and I feel fortunate and honored to be invited to participate and asked to give a keynote presentation. Australia is a beautiful place and Diane and I had a dream trip, so thank you. We felt the AD field transforming into a vibrant treatment-oriented specialty, using all the tools of modern medicine. In the future we will be screening people in mid-life and instituting treatments to prevent AD in those at higher risk. Australian researchers are making amazing contributions to move the field forward.

What are the next steps in your career?

I take the vow to protect patient safety very seriously as we roll out the new amyloid-lowering treatments. I want to ensure that we adopt high standards of clinical practice and use common sense to limit serious outcomes. I also want to stay connected with colleagues, patients and families to carry on the global fight against AD. I wish ADNeT great success and we look forward to collaborating with you.

* Donanemab has since been approved by the FDA. This interview was conducted shortly before the approval.

Below: Dr Salloway presents his keynote address at the Australian Dementia Research Forum 2024