Real-world registry sits at the center of this dementia and brain health question.

The Alzheimer’s Association launched ALZ-NET—the Alzheimer’s Network for Treatment and Diagnostics—in late 2021 as the first nationwide patient registry designed to track real-world outcomes of FDA-approved Alzheimer’s therapies outside of controlled clinical trials. This registry captures how these medications actually perform in everyday clinical practice, collecting data from 118 active clinical sites across the country on more than 3,600 enrolled patients. Rather than relying solely on data generated during formal drug trials, ALZ-NET bridges the gap between what researchers observe in the lab and what patients and doctors experience in their own communities.

The registry has grown to enroll approximately 50 new patients per week, and for the first time in December 2025, researchers presented major findings from over 600 patients receiving anti-amyloid targeting therapies. These initial results provide crucial insight into how treatments like Leqembi and donanemab are working in real patients—information that’s directly changing how neurologists approach Alzheimer’s care. This article explores what ALZ-NET is, what its early data reveals, and what it means for patients and families considering or already using these treatments.

What Is ALZ-NET and How Does It Differ from Clinical Trials?
What Real-World Safety and Efficacy Data Is ALZ-NET Revealing?
Understanding ARIA—The Side Effect All Caregivers Should Know About
What FDA-Approved Treatments Are Being Monitored?
What Do ALZ-NET Demographics Tell Us About Who Is Being Treated?
International Expansion—Why ALZ-NET Is Going Global
What ALZ-NET Means for Future Alzheimer’s Care
Conclusion

What Is ALZ-NET and How Does It Differ from Clinical Trials?

ALZ-NET functions as a nationwide registry where participating clinics and hospitals systematically document patient information, treatment details, and outcomes over time. Unlike clinical trials, which involve strictly controlled patient populations, precise dosing schedules, and frequent monitoring visits, ALZ-NET captures messy, real-world data. Patients enrolled in the registry represent the actual people walking into neurologists’ offices—people with varying ages, lifespans, comorbidities, and adherence patterns. The registry currently includes 118 participating clinical sites and is expanding through collaborative partnerships internationally.

A key strength of ALZ-NET is its ability to answer questions that clinical trials cannot. For example, clinical trials often exclude older patients with multiple medical conditions, yet many real patients starting anti-amyloid therapies fall into exactly these categories. ALZ-NET data shows what happens to these more complex patients when they receive these medications. The registry also captures long-term outcomes, subtle side effects, and discontinuation patterns that might not emerge during a 12-month or 18-month trial. Enrollment continues to grow rapidly, demonstrating broad clinical interest in contributing real-world evidence as new Alzheimer’s treatments become available.

What Is ALZ-NET and How Does It Differ from Clinical Trials?

What Real-World Safety and Efficacy Data Is ALZ-NET Revealing?

The first major data readout, presented at the Clinical Trials on Alzheimer’s disease (CTAD) Conference on December 3, 2025, examined 600 patients enrolled in ALZ-NET who were receiving anti-amyloid targeting therapies. The critical finding was reassurance: safety and effectiveness in real-world patients aligned closely with results from the controlled clinical trials used to approve these medications. This matters because it confirms that the benefits doctors saw in trials actually translate to community practice, where patient populations are more diverse and conditions less controlled. Cognitive and functional measures remained stable during the first year of anti-amyloid therapy for these patients, meaning people did not experience worsening of memory or daily functioning during treatment—a baseline achievement that was critical to establish.

The demographic makeup of ALZ-NET participants closely resembled trial participants, suggesting the registry is enrolling a representative population. However, there is an important limitation: most individuals being treated with anti-amyloid therapies in this dataset were in early clinical stages of Alzheimer’s disease. This reflects current prescribing patterns—doctors are primarily offering these medications to people with mild cognitive impairment or mild dementia, not advanced cases. As enrollment continues, the registry may provide data on outcomes in later-stage disease, though this remains an open question.

Understanding ARIA—The Side Effect All Caregivers Should Know About

Among the most closely monitored aspects of anti-amyloid therapy are amyloid-related imaging abnormalities, or ARIA. These are brain changes visible on MRI scans that can occur when the immune system is activated to remove amyloid plaques. ARIA comes in two main forms: ARIA-E (amyloid-related imaging abnormalities of edema, which is brain swelling), and ARIA-H (microhemorrhages, or tiny bleeds). Both sound alarming, but the actual clinical significance varies considerably. Some people experience no symptoms at all from ARIA, while others develop headaches, confusion, or vision problems.

ALZ-NET’s data on ARIA is largely reassuring. The rates of ARIA observed in real-world patients aligned with the rates predicted from clinical trials based on factors like the specific medication used and a person’s apolipoprotein E status—a genetic factor that influences Alzheimer’s risk and ARIA susceptibility. Most importantly, no ARIA-related deaths were reported among the 600-plus patients in the dataset during the first year of treatment. However, this does not mean ARIA is risk-free. Patients on these therapies require regular MRI monitoring, typically every 6 to 12 months, and neurologists must remain vigilant for subtle cognitive or physical changes that might signal ARIA requiring dose adjustment or treatment discontinuation. The message is balanced: ARIA is manageable but real, and ongoing monitoring is non-negotiable.

Understanding ARIA—The Side Effect All Caregivers Should Know About

What FDA-Approved Treatments Are Being Monitored?

ALZ-NET tracks real-world use of multiple FDA-approved anti-amyloid therapies, each with a different profile. Leqembi (lecanemab), manufactured by Eli Lilly and Eisai, received initial FDA approval in July 2023 and has since gained additional approvals for simplified administration: intravenous maintenance dosing once every four weeks (approved January 2025) and once-weekly subcutaneous injection (approved August 2025). These newer approval pathways reduce the burden of treatment by requiring fewer clinic visits or eliminating the need for IV infusions altogether. Donanemab (Kisunla), manufactured by Eli Lilly, received FDA approval on July 2, 2024, and carries a unique distinction: it’s the first Alzheimer’s medication approved with evidence suggesting patients can actually stop treatment once amyloid plaques are cleared from the brain, potentially making it a finite course of therapy rather than indefinite treatment.

Aducanumab (Aduhelm), the first anti-amyloid monoclonal antibody approved by the FDA, received conditional approval in June 2021 but was later discontinued in November 2024 following sluggish adoption and medical community skepticism about its efficacy. ALZ-NET includes historical data on some aducanumab patients, providing insights into outcomes with the first-generation therapy. For patients and families deciding between treatments, the key considerations include the administration method (IV infusion vs. subcutaneous injection), frequency of dosing, local availability, and insurance coverage. Donanemab’s potential for treatment completion is attractive to some patients but remains a newer development with less long-term real-world data than Leqembi.

What Do ALZ-NET Demographics Tell Us About Who Is Being Treated?

ALZ-NET participants receiving anti-amyloid therapy are demographically similar to those who enrolled in the clinical trials that led to FDA approval. This similarity is important because it validates that real-world prescribers are appropriately identifying and treating the patients most likely to benefit. The data also reveals that most participants are in early clinical stages—mild cognitive impairment or mild dementia—reflecting current clinical practice guidelines that recommend these medications early in the disease course when there is still significant cognitive reserve.

However, a critical gap remains: how do these therapies work in older adults with multiple medical conditions, in people who cannot tolerate frequent MRI monitoring, or in those from racial and ethnic groups historically underrepresented in clinical research? While ALZ-NET enrollment is growing, the demographic profile suggests that current enrollment may still skew toward healthier, younger, and more medically stable patients relative to the general population living with Alzheimer’s. This is not a condemnation of ALZ-NET but rather a recognition that real-world registries inherit enrollment biases from clinical practice itself. Ongoing expansion of the registry, particularly into primary care settings and diverse communities, will help address this limitation.

What Do ALZ-NET Demographics Tell Us About Who Is Being Treated?

International Expansion—Why ALZ-NET Is Going Global

The success of ALZ-NET within the United States has catalyzed international expansion. The Alzheimer’s Association is funding parallel registries in multiple countries, including Australia (ADNeT, led by Dr. Christopher Rowe at the University of Melbourne), the Netherlands (ABOARD Cohort, led by Dr. Casper de Boer at Amsterdam University Medical Center), and Chile (University of Chile, Santiago).

These international partners are building registries adapted to their own healthcare systems while maintaining compatibility with the U.S. ALZ-NET framework. ALZ-NET International holds quarterly meetings with collaborators representing Australia, Germany, Iceland, Japan, the Netherlands, South Korea, Sweden, Turkey, the United Kingdom, and the United States. This global network allows researchers to answer questions about regional differences in treatment prescribing, healthcare access, and outcomes across different populations and healthcare structures. For example, how does early detection and treatment access differ between countries with universal healthcare versus insurance-based systems? How do cultural attitudes toward amyloid-lowering therapy vary internationally? These questions are becoming increasingly important as anti-amyloid medications diffuse globally, and ALZ-NET International positions researchers to answer them.

What ALZ-NET Means for Future Alzheimer’s Care

As ALZ-NET continues to grow—currently enrolling approximately 50 new patients per week—the accumulating data will increasingly inform clinical guidelines, prescribing patterns, and treatment expectations. The registry is approaching a critical inflection point: from a descriptive data-gathering phase to a hypothesis-testing phase where researchers can examine specific questions about long-term outcomes, treatment discontinuation, combination therapies, and rare adverse events. With over 3,600 patients already enrolled and expansion to 118 sites nationwide, ALZ-NET provides a foundation for the kind of large-scale, real-world evidence that transforms medical practice.

The future of ALZ-NET also hinges on sustained participation and data quality from clinical sites, many of which are managing ALZ-NET alongside their regular patient care with minimal dedicated funding. Continued investment and recognition of the sites’ contributions will be essential to maintaining enrollment momentum. As newer anti-amyloid agents and other disease-modifying therapies are developed and approved, ALZ-NET will be positioned to rapidly integrate them into the registry, creating a living archive of real-world Alzheimer’s treatment for decades to come.

Conclusion

The ALZ-NET registry represents a fundamental shift in how we understand Alzheimer’s disease treatment in everyday clinical practice. By systematically collecting data from 118 sites across more than 3,600 patients, the registry confirms that anti-amyloid therapies deliver safety and efficacy consistent with clinical trials while also documenting the texture of real-world care—the patients who are actually being treated, the outcomes they experience, and the challenges clinicians face. The first major data readout in December 2025 provided reassurance that these medications are working as expected, though ongoing monitoring for ARIA and continued demographic expansion remain important priorities.

If you or a family member is living with Alzheimer’s disease and considering treatment with Leqembi, donanemab, or other anti-amyloid therapies, ask your neurologist whether they participate in ALZ-NET and whether enrollment might be an option. Even if direct participation isn’t possible, the data emerging from the registry will inform your doctor’s decision-making and help ensure that treatment recommendations are grounded in real-world evidence. As ALZ-NET expands globally and incorporates additional medications and patient populations, it will continue to shape the landscape of Alzheimer’s care for years to come.