An MRI Pilot Study of Bariatric Surgery to Reduce Risk of Alzheimer’s Disease

Project Summary:

Midlife obesity is a major health priority in Wisconsin, affecting 33.9% of adults and 55.1% of Black/African American adults. Obesity promotes chronic inflammation and oxidative stress that damage the cerebrovascular system, an early pathway linking metabolic disease to Alzheimer’s disease (AD). Yet in Wisconsin, obesity, metabolic disease, and brain health are treated in silos. Addressing obesity as a modifiable neurovascular risk factor represents a critical opportunity to reduce future dementia burden and advance health equity. This proof-of-concept study establishes a novel brain–metabolic health framework by testing whether sleeve gastrectomy (SG), the most effective and durable treatment for severe obesity, modifies early neurovascular and inflammatory pathways associated with cognitive decline. The project team's prior work demonstrates that SG favorably shifts systemic redox biology, increasing ceruloplasmin (an inhibitor of myeloperoxidase [MPO]) and reducing circulating MPO, a neutrophil-derived pro-inflammatory enzyme that disrupts the blood-brain barrier and promotes neuroinflammation. They will enroll midlife adults with severe obesity undergoing SG and assess changes from pre-surgery to six months post-surgery. They hypothesize that SG-mediated reductions in oxidative stress will improve neurovascular function and stabilize or enhance cognition. This project bridges metabolic surgery, neurovascular biology, and health equity to create a Wisconsin-based model for early AD risk modification.