Grant: Project Grant

Alzheimer's disease impairs memory and thinking, but it does not progress the same way for everyone. Some people decline quickly, while others stay stable for years. Scientists have discovered that sex, the biological differences between males and females, plays a major role in this variability. Gender, as a socio-cultural variable, also plays a role. Females are more likely to develop AD and experience faster memory decline than males, even when they have the same levels of harmful brain proteins, like amyloid and tau. However, we don't fully understand why. Our project brings together data from over 10,000 people across eight major studies, using brain scans (MRI and PET), spinal fluid tests, and memory tests. We will study the pathways by which sex and gender affect the buildup of amyloid and tau proteins, brain shrinkage, and memory decline. Alzheimer's disease is the most common cause of dementia, affecting more than half a million Canadians today, and this number will rise sharply as our population ages. Understanding sex and gender effects are critical for developing more personalized and equitable approaches to prevention and care. We will also create a new tool called a "Digital Twin" to predict how memory and thinking may decline in new patients. Just as a doctor compares a new patient to past patients with similar symptoms, a digital twin compares each individual to a set of "virtual twins", i.e., previous patients drawn from a large database. This tool can make Alzheimer's trials more efficient by boosting power to detect treatment effects, enabling faster completion with smaller patient groups. By combining cutting-edge statistical modeling with careful attention to sex and gender, this project aims to improve our understanding of why females are more affected by Alzheimer's disease, give doctors better tools to predict memory decline, and ultimately speed the search for effective treatments for patients and their families.