Gayatri Devi, MD, MS, FACP, FAAN

Managing Amyloid-Related Imaging Abnormalities in Alzheimer Disease

ARIA, or amyloid-related imaging abnormalities, refer to brain changes that can occur in patients receiving monoclonal antibody treatments targeting amyloid plaques. These abnormalities include brain swelling, called edema, and bleeding, known as hemorrhage. They result from the breakdown of the blood-brain barrier caused by the removal of amyloid deposits, leading to fluid leakage and potential bleeding. ARIA with edema (ARIA-E) occurs in up to 40% of treated patients and can be life-threatening, while ARIA hemorrhage (ARIA-H) involves bleeding within the brain tissue. The risk is higher in patients with the 

 gene, especially those with 2 copies, making careful monitoring essential during therapy.

Monitoring for ARIA involves routine MRI scans before and during treatment, typically every few months. Most cases are asymptomatic and discovered incidentally on imaging, although some patients may experience symptoms like headaches, confusion, weakness, or numbness, mimicking stroke. To mitigate risks, clinicians often start with low doses of monoclonal antibodies and gradually increase them, which has been shown to reduce the incidence of ARIA. In case of ARIA development, treatments such as corticosteroids can be used to reduce inflammation, and the abnormalities tend to resolve over time, especially in cases of edema. Patients are advised to wear identification bracelets indicating they are on these therapies, so emergency physicians are aware and avoid potentially harmful treatments like tissue plasminogen activator, which could cause fatal bleeding if administered during an active ARIA.

Understanding the mechanism behind ARIA involves recognizing how removing amyloid from blood vessel walls causes fluid and blood components to leak into surrounding brain tissue. Managing blood pressure and inflammation can help reduce the severity of ARIA episodes. While the current approach emphasizes careful monitoring and supportive care, ongoing research aims to develop safer, more effective therapies with fewer adverse effects. The development of imaging and biomarker strategies continues to improve early detection and management, making these treatments increasingly feasible for broader patient populations.

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Panelists discuss how amyloid-related imaging abnormalities, including brain swelling and bleeding, can occur in patients receiving monoclonal antibody therapies for Alzheimer disease, necessitating careful monitoring through MRI scans, dose adjustments, and supportive care to manage risks—particularly in individuals with genetic risk factors—while ongoing research seeks safer, more effective treatments and improved detection strategies.

Treatment Options and Disease-Modifying Therapies in Alzheimer Disease

Current treatment options for Alzheimer disease encompass both pharmacologic and nonpharmacologic strategies. Medications include cholinesterase inhibitors, such as donepezil and rivastigmine, which boost brain acetylcholine levels to enhance nerve communication. Another class involves NMDA receptor antagonists like memantine, which modulate glutamate activity to protect neurons. Recently approved monoclonal antibodies, such as donanemab and lecanemab, target amyloid plaques directly, offering disease-modifying potential with intravenous infusions every 2 weeks or monthly. Besides these, emerging therapies like metformin, antivirals, and blood pressure control medications are being explored for their neuroprotective effects, aiming to modulate disease progression.

In addition to medications, a holistic approach emphasizes lifestyle modifications and supportive therapies. Physical activity, cognitive exercises, and social engagement help maintain neural networks and functional independence. Optimizing sleep—using new classes like orexin inhibitors—can reduce plaque accumulation and improve memory consolidation. Managing comorbidities, including hearing loss and depression, also plays a vital role in delaying cognitive decline. These nondrug interventions, combined with medical treatments, aim to preserve quality of life, delay institutionalization, and enhance overall brain health.

The advent of disease-modifying therapies, especially monoclonal antibodies, has reinvigorated the outlook on Alzheimer management. While their approval has not drastically changed diagnostic thresholds, it provides clinicians with new tools to offer hope and early intervention opportunities. Physicians now feel more empowered to detect the disease sooner and initiate treatments that can slow or potentially prevent progression. Ongoing research, supported by advances like artificial intelligence–driven drug discovery, promises even more effective and less invasive options in the future, such as subcutaneous injections administered at home. These developments mark a transformative era in the fight against Alzheimer, making early detection and proactive management more critical than ever.

Panelists discuss how current Alzheimer treatments combine pharmacologic options like cholinesterase inhibitors, NMDA antagonists, and recently approved monoclonal antibodies with nonpharmacologic strategies such as lifestyle modifications, cognitive engagement, and managing comorbidities, all aiming to preserve quality of life, delay progression, and harness new therapies that are transforming the outlook for early diagnosis and proactive management.

Referring Patients with Alzheimer Disease to Neurologists and Improving Patient Communication

Frontline clinicians often have a low threshold for referring patients to neurologists or memory specialists, especially when early signs or strong family histories raise suspicion. They prioritize early intervention, recognizing that prompt referral can lead to more effective management and better outcomes. Typically, they consider subtle changes such as minor memory lapses, reduced executive function, or behavioral shifts. When available, they utilize genetic testing like for 

, along with neurocognitive assessments, to identify at-risk individuals. Even if the findings are minor, they prefer to err on the side of caution, understanding that early diagnosis allows for lifestyle modifications, clinical trials, or emerging therapies that can slow disease progression.

Effective communication about referral decisions involves building trust and using a thoughtful approach. Providers often use humor or light conversation to lessen patients’ anxiety and to encourage openness about cognitive concerns. They emphasize that early detection is not a death sentence but a chance to access new treatments and supportive resources. Explaining that many cognitive changes are normal with aging, but that some signs warrant further evaluation, helps patients feel supported rather than alarmed. Providing reassurance and highlighting the benefits of early diagnosis—such as establishing baselines for future comparison—facilitates acceptance of referral to specialists.

Barriers to timely referrals include logistical issues like cost, insurance coverage, and appointment availability. Many patients face challenges scheduling appointments with specialists due to busy calendars or transportation issues. To improve the process, clinicians can provide clear information about insurance coverage, including Medicare, and advocate for their patients’ access to care. Additionally, primary care providers can frame questions to encourage patients to open up, using humor or empathetic language to reduce stigma. Establishing a trusting relationship and normalizing concerns about cognition help patients feel more comfortable discussing their worries, making them more receptive to evaluation and treatment options. Creating seamless pathways for referral and education about the importance of early detection remain vital for optimizing patient care.

Panelists discuss how frontline clinicians tend to refer patients promptly to specialists when early cognitive signs or family history suggest risk, emphasizing the importance of early intervention, clear communication, and addressing logistical barriers to ensure timely diagnosis and access to emerging treatments that can slow disease progression.

Leveraging Patient Trust to Improve Outcomes in Alzheimer Disease

Long-standing relationships between clinicians and patients are invaluable for early detection of cognitive decline. Trust built over years allows physicians to notice subtle changes in behavior, hygiene, or mood that patients or their families might overlook or dismiss. For instance, a clinician familiar with a patient’s normal routines and appearance can gently raise concerns about memory lapses or personality shifts, encouraging timely screening. Because patients trust their providers, discussions about cognitive health become collaborative, reducing fear and stigma, and making it easier to initiate early assessments and interventions.

Leveraging these relationships also involves continuous observation over time. A clinician might notice gradual signs—such as increased forgetfulness or changes in style and grooming—that, when discussed openly, can lead to earlier diagnosis. Sharing stories of patients who were monitored over years highlights how early subtle cues, if recognized sooner, could have prompted earlier testing or referrals. These ongoing interactions foster a sense of partnership, where the patient and provider work together in managing health. When families are involved, clinicians can also better understand the patient’s baseline, making it easier to detect meaningful changes and provide reassurance or guidance.

Ultimately, long-term relationships provide a foundation for proactive, preventive care. Trust encourages patients to be honest about their concerns, and clinicians can tailor screening and education to individual needs. This ongoing rapport makes it easier to introduce lifestyle modifications, cognitive assessments, and planning before symptoms severely impair quality of life. As the aging population grows—projected to double over age 65 years by 2050—these relationships become even more critical. They enable early detection, timely interventions, and sustained support, helping patients maintain independence and dignity longer while easing the societal burden of dementia care.

Panelists discuss how long-standing relationships between clinicians and patients are essential for early detection of cognitive decline, as trust and familiarity enable providers to notice subtle changes, facilitate open conversations, and collaboratively implement early interventions that help preserve independence amid an aging population.

Gayatri Devi, MD, MS, FACP, FAAN

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