STRATA-ALZ · Optimizing stratification for trial design in Alzheimer’s disease

Optimizing stratification for trial design in Alzheimer’s disease

Background Dementia is one of the greatest health challenges of our time. It causes major disability and dependence in older adults, and the number of people affected is growing rapidly. By 2050, an estimated 150 million people could be living with dementia worldwide. This has an enormous emotional and financial impact on families, healthcare systems, and society. The most common cause of dementia is Alzheimer’s disease (AD)—a brain disorder that begins quietly, with harmful changes starting many years before symptoms like memory loss appear. These early changes involve the buildup of specific proteins (amyloid and tau), which eventually damage brain cells and lead to cognitive decline. We now know that a large portion of people over 50 already show early signs of these changes, even before they feel any symptoms. This means there is a huge opportunity to intervene earlier—before the damage becomes irreversible. But to succeed, we need better tools to identify and group the right people for the right treatments in clinical trials. The Problem: Why dementia trials often fail Despite major investments in research, most clinical trials for Alzheimer’s treatments have not been successful. One key reason is that these trials often include participants who are too far along in the disease, or whose disease is driven by different biological factors. Alzheimer’s is not a one-size-fits-all condition. People with the disease can differ widely in terms of symptoms, underlying biology, and other health problems like vascular disease. If these differences aren't accounted for, it becomes very hard to detect whether a treatment is truly working. In other words, poor patient selection and grouping ('stratification') can mask the effects of promising treatments. Recent trials that did show some success used smarter ways to group participants based on brain imaging. This shows that more personalized approaches to trial design can make a real difference—and that's exactly what this project aims to achieve. The Project Goal: Tailoring trials to people’s unique disease patterns This project aims to optimize how people are selected and evaluated in Alzheimer's clinical trials, especially in the earliest stages of the disease (before or just as symptoms appear). By better understanding and categorizing the different ways the disease progresses, we can: 1. Identify distinct disease "pathways"—for example, whether a person’s Alzheimer’s is mainly driven by protein buildup, blood vessel damage, or both. 2. Use this information to form more precise participant groups in trials. 3. Improve how treatment effects are measured by choosing the right cognitive tests and brain scans based on each disease subtype. To do this, I will analyze data from over 2,900 participants in the BioFINDER studies—world-leading Swedish research studies that track brain health over time using advanced imaging, blood and spinal fluid tests, and cognitive assessments. As such, the project will map out different biological subtypes of early Alzheimer’s using imaging data (e.g. brain scans that show protein buildup or small vessel disease), explore new fluid biomarkers that reflect brain health and immune activity, using cutting-edge protein analysis tools, and match disease subtypes with specific patterns of cognitive decline, to improve how we measure treatment success in future trials. Why it matters and what I aim to achieve: This project comes at a crucial moment in the global effort to tackle dementia, a condition that is not only devastating for individuals and families but also poses a growing challenge for healthcare systems. This project directly addresses that problem by bringing a more personalized, data-driven approach to how we design and run clinical trials. By better understanding the different ways Alzheimer’s can develop, and by matching participants to the right trials based on their specific disease pathway, we can significantly improve the chances of detecting true treatment effects. In turn, this means we can move faster and more confidently toward therapies that work. Beyond its scientific innovation, the project also aligns with broader health and policy goals. It supports the push for earlier diagnosis, personalized medicine, and smarter, more efficient use of healthcare resources. The potential impact is significant: improving how we test treatments could accelerate the arrival of therapies that delay or even prevent dementia. This would not only improve quality of life for millions of people but also reduce the long-term societal and economic burden of the disease. In short, by tailoring clinical trials to the biological reality of Alzheimer’s disease, this project aims to change the way we fight dementia—making the path to effective treatments clearer, faster, and more successful.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз