A study from the University of California, Irvine’s Center for the Neurobiology of Learning and Memory has found that changes in the overall shape of the brain during aging are closely linked to memory loss and dementia risk. The research, published in Nature Communications, used a new analytic method to track how the brain’s form shifts over time rather than focusing only on the size of specific regions.
Researchers analyzed more than 2,600 brain scans from adults aged 30 to 97. They observed that as people age, certain parts of the brain expand outward while others contract inward. These geometric changes were most pronounced in older adults experiencing cognitive decline. The findings were consistent across two independent datasets.
“Most studies of brain aging focus on how much tissue is lost in different regions,” said Niels Janssen, PhD, senior author and professor at Universidad de La Laguna in Spain and visiting faculty at the CNLM. “What we found is that the overall shape of the brain shifts in systematic ways, and those shifts are closely tied to whether someone shows cognitive impairment.”
The study highlighted that individuals with more compression in the posterior part of their brains had poorer reasoning skills. This suggests a direct correlation between these shape changes and cognitive function.
One key finding involved the entorhinal cortex, a region important for memory located in the medial temporal lobe. The researchers suggest that age-related shape changes may push this vulnerable area closer to the base of the skull. Since this region is one of the first affected by tau protein buildup—a hallmark of Alzheimer’s disease—the team proposes that mechanical forces could play a role in its vulnerability.
“This could help explain why the entorhinal cortex is ground zero of Alzheimer’s pathology,” said study co-author Michael Yassa, PhD, director of the CNLM and James L. McGaugh Endowed Chair. “If the aging brain is gradually shifting in a way that squeezes this fragile region against a rigid boundary, it may create the perfect storm for damage to take root. Understanding that process gives us a whole new way to think about the mechanisms of Alzheimer’s disease and the possibility of early detection.”
The researchers believe their approach could lead to new ways to identify dementia risk before symptoms appear.
“This isn’t just about measuring brain shrinkage,” added Janssen. “It’s about seeing how the brain’s architecture responds to aging and how that architecture predicts who is more likely to struggle with memory and thinking.”
The project was conducted through collaboration between UC Irvine and Universidad de La Laguna in Spain, with Yuritza Escalante and Jenna Adams, PhD, as co-first authors.
“We’re just beginning to unlock how brain geometry shapes disease,” said Yassa. “But this research shows that the answers may be hiding in plain sight – in the shape of the brain itself.”
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