Cross-Sectional and Longitudinal Network Degradation in Genetic and Sporadic AD

Jasmeer Chhatwal, MD, PhD Massachusetts General Hospital


Reisa Sperling, MD Brigham and Women's Hospital


The goal of this study is to better differentiate normal aging and early Alzheimer’s disease (AD) by using MRI and PET imaging to examine the health of neural networks that allow us to store and retrieve memories. In addition to providing us with a better fundamental understanding of how neurodegenerative diseases like AD affect the brain, these studies will refine the use of imaging techniques in clinical trials and thereby improve drug development in AD.

Dr. Chhatwal and his research colleagues are very fortunate to have access to a large amount of imaging data from young individuals with genetic mutations that inevitably lead to early-onset dementia (often at age 40-50) who are participating in the Dominantly Inherited Alzheimer Network (DIAN) study, an international consortium led by investigators at Washington University in St. Louis. These data will be compared with imaging data from a wide variety of individuals, including cognitively normal young and older adults, as well as older individuals with Mild Cognitive Impairment and Alzheimer’s disease. With these unique and diverse datasets, and using novel analytic tools that were developed by Dr. Chhatwal and his colleagues, they can ask questions about how aging affects the brain and whether these changes are fundamentally different from those seen in AD.

This study makes use of four main types of imaging: (1) Functional connectivity MRI, to determine which parts of the brain are working together in networks; (2) Structural MRI, to very accurately measure the size of each fold and region of the brain; (3) Amyloid PET, to measure how much amyloid (the protein that clumps together to form plaques in brains of patients with AD) is in the brain; and (4) FDG PET, to see how much glucose (sugar) is used in each part of the brain. Together with information about memory performance by each of the subjects, these types of images provide a uniquely detailed picture of the brain’s health in normal and impaired subjects. By combining the information from these different types of imaging, Dr. Chhatwal and his colleagues will identify patterns of brain changes that indicate the earliest stages of AD, and use this information to determine the efficacy of experimental medications in Alzheimer’s prevention trials.

Dr. Chhatwal is very grateful for the participation of the many research subject volunteers, and for the support of those willing to provide funding for these exciting studies.

Project Details

The purpose of this study is to use an advanced brain imaging technique to understand how aging and Alzheimer's disease degrade the brain networks that allow us to form and recall memories. These studies will help tell us how aging and Alzheimer's disease differ, and allow us to better design clinical trials for treatment of Alzheimer's disease. Also, these studies will help us to understand why older people without Alzheimer's disease may have memory problems as they age, a phenomenon some call "age-related cognitive decline."