Brain shape changes could offer early warning signs of dementia, study suggests

Ageing alters the brain’s shape in measurable ways that could provide early warning signs of dementia, potentially years before symptoms appear, researchers say.

Analysis of more than 2,600 brain scans from adults aged 30 to 97 revealed significant alterations in brain geometry linked to declines in memory, reasoning and other cognitive functions.

The inferior and anterior parts of the brain expanded outward, while the superior and posterior regions contracted inward. These uneven shifts were most evident in older adults showing cognitive decline.

Researchers at the University of California, Irvine’s Centre for the Neurobiology of Learning and Memory found that people with more pronounced posterior compression performed worse in reasoning tests, suggesting these geometric markers directly relate to brain function.

“Most studies of brain ageing focus on how much tissue is lost in different regions,” said Niels Janssen, 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.”

One important implication involves the entorhinal cortex – a small but vital memory hub in the medial temporal lobe.

The study suggests age-related reshaping may press this region against the hard base of the skull.

The entorhinal cortex is one of the first areas where tau, a toxic protein linked to Alzheimer’s disease, accumulates.

The findings raise the possibility that mechanical and gravitational forces may contribute to its vulnerability in Alzheimer’s – a potential disease mechanism not previously considered.

“This could help explain why the entorhinal cortex is ground zero of Alzheimer’s pathology,” said study co-author Michael Yassa, director of the CNLM and James L McGaugh endowed chair.

“If the ageing 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. U

“nderstanding 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 say their geometric approach could eventually provide new markers for identifying dementia risk, potentially before symptoms emerge.

“This isn’t just about measuring brain shrinkage,” added Janssen.

“It’s about seeing how the brain’s architecture responds to ageing and how that architecture predicts who is more likely to struggle with memory and thinking.”

The patterns were replicated in two independent datasets, reinforcing the consistency of these shape changes as a hallmark of ageing.

“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.”