Q&A: Stephen Salloway, MD, MS | Amyloid-related imaging abnormalities are on the rise
New treatments could help curb the trend in Alzheimer’s patients.
Data in recent years has shown an increasing trend in amyloid-related imaging abnormalities (ARIA) in patients with Alzheimer’s disease being treated with amyloid-lowering monoclonal antibodies, such as lecanemab and donanemab. One of the leading researchers in this area is Stephen Salloway, MD, MS, founding director of the Memory and Aging Program (MAP) at Butler Hospital in Providence, Rhode Island, and professor of neurology and psychiatry at Warren Alpert Medical School of Brown University.
For more than 25 years, Dr. Salloway has conducted more than 125 clinical trials related to Alzheimer’s disease. At Butler Hospital’s MAP, he and his team have played a part in many major breakthroughs in Alzheimer’s diagnosis and treatment. His research has included studying ways to predict who is at risk for Alzheimer’s disease, developing approaches to prevent or slow its development through lifestyle modifications and identifying better diagnostic tests to promote early detection and treatment breakthroughs.
The MAP has helped pioneer the use of PET ligands for amyloid and tau to study the evolution of Alzheimer’s pathophysiology in autosomal dominant and sporadic Alzheimer’s disease. The program has played a lead role in testing treatments, such as monoclonal antibodies, to lower amyloid plaques and neurofibrillary tangles, as well as tested approaches, such as deep brain stimulation and antisense oligonucleotides, to slow the progression of Alzheimer’s.
Dr. Salloway will present his findings during the Friday session, ARIA: Vascular Manifestations of Amyloid Immunotherapy, as well as during a Meet the Expert session Wednesday afternoon on Zoom. He shared some of his experiences with ISC News prior to the #ISC24 meeting.
ISC News: You’ve done a lot of research in the field of ARIA in Alzheimer’s patients. What is your background in the area?
Dr. Salloway: I am a neurologist and clinical trialist studying new treatments and biomarkers for Alzheimer’s disease. The goal is to treat Alzheimer’s like other major diseases with an early and accurate diagnosis and treatments to slow the disease and preserve quality of life.
ISC News: When did you first discover these abnormalities in Alzheimer’s patients?
Dr. Salloway: We first reported the side effect of edema and microhemorrhage with treatment with amyloid-lowering antibodies in 2009 when testing bapineuzumab for mild to moderate Alzheimer’s disease. These changes are now known as amyloid-related imaging abnormalities, or ARIA, and are seen with all monoclonal antibodies that target amyloid plaques. The term ARIA-E is used for edema and ARIA-H for hemorrhagic changes.
ISC News: How do the abnormalities present in terms of symptoms?
Dr. Salloway: These changes typically occur early in treatment and are usually transient and asymptomatic. ARIA is symptomatic in 25% of patients. Symptoms are usually mild and non-specific and can include headache, confusion, dizziness and unsteadiness. However, more serious events can occur, which resemble cerebral amyloid angiopathy-related inflammation, and can lead to seizures and focal neurological signs and can be fatal.
ISC News: What do these discoveries mean in treating Alzheimer’s patients going forward?
Dr. Salloway: There will soon be two amyloid-lowering antibodies with full FDA approval available for early Alzheimer’s disease. As amyloid-lowering antibodies roll out into clinical practice, clinicians and radiologists need to be able to detect and manage ARIA to limit more serious outcomes.
ISC News: What do physicians need to be on the lookout for when it comes to spotting these abnormalities?
Dr. Salloway: The main risk factors for more serious ARIA are the number of ApoE4 alleles and evidence of cerebral amyloid angiopathy on MRI. When evaluating patients in the emergency setting with a focal presentation suggestive of stroke, hospital personnel need to be aware that patients are receiving an amyloid-lowering antibody, consider ARIA in the differential diagnosis, know the patient’s ApoE genotype, if available, carefully stage the imaging evaluation and try to limit the use of treatment with thrombolytics. Prompt empiric treatment with high-dose corticosteroids and monitoring and treatment for seizures may be needed for more serious cases.
