Brain Shape Shifts Linked to Memory Decline and Dementia Risk

Aging causes systematic changes in brain shape that may offer a new avenue for detecting early signs of dementia, according to researchers at the University of California, Irvine (UC Irvine). The study, published in Nature Communications, presents a novel approach that shifts focus from brain volume loss in isolated regions to broader structural deformation over time.

Researchers from UC Irvine’s Center for the Neurobiology of Learning and Memory, in collaboration with Universidad de La Laguna in Spain, analyzed more than 2,600 brain scans from adults aged 30 to 97. Using a recently developed computational framework, they quantified geometric shifts in the brain rather than measuring the size of individual regions.

Uneven shape changes correspond with cognitive decline

The team observed that specific areas of the brain underwent distinct movements as people aged. Inferior and anterior regions tended to expand outward, while superior and posterior regions contracted inward. These asymmetrical changes were more pronounced in individuals showing cognitive impairment.

One key finding was the association between increased compression in posterior brain regions and reduced reasoning ability. These shape alterations were observed consistently across two independent datasets, suggesting that the changes are a reliable marker of cognitive aging.

Structural stress on memory-related regions

The study also examined how these shape shifts may affect the entorhinal cortex, a small structure in the medial temporal lobe involved in memory. This region is among the first to accumulate tau, a protein associated with Alzheimer’s disease.

The research suggests that age-related shape changes could physically displace the entorhinal cortex toward the base of the skull. This proximity to a rigid boundary may subject it to mechanical stress, potentially increasing its vulnerability to degeneration. These findings raise the possibility that gravitational and mechanical forces, previously unconsidered, contribute to the early pathology of Alzheimer's disease.

Implications for early detection

By emphasizing geometry over tissue loss, the study proposes a complementary method for assessing brain health. These shape-based markers may one day aid in identifying individuals at higher risk of dementia before clinical symptoms become apparent.

The work was led by co-first authors Yuritza Escalante and Jenna Adams, PhD, and supported by the National Institute on Aging, part of the National Institutes of Health.

Reference: Escalante YY, Adams JN, Yassa MA, Janssen N. Age-related constraints on the spatial geometry of the brain. Nat Commun. 2025. doi:10.1038/s41467-025-63628-3

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