Summary: A new study finds that aging changes not only the size but also the overall shape of the human brain, with measurable patterns of expansion and compression that relate directly to declines in memory, reasoning and other cognitive abilities. Researchers observed outward bulging in lower and front regions and inward compression in upper and back regions, and these geometric shifts correlate with cognitive performance and vulnerability to Alzheimer’s-related pathology.
Rather than examining only regional atrophy, the team applied a novel analytic approach to quantify how the brain’s global geometry warps with age. Their results point to brain shape as a promising biomarker for identifying neurodegenerative risk long before clinical symptoms emerge.
Key Facts:
- Shape over size: Aging produces systematic expansions and compressions across the brain’s surface that reveal more than volume loss alone.
- Alzheimer’s link: Geometric changes may place mechanical stress on the entorhinal cortex, an early site of Alzheimer’s pathology.
- Early detection potential: Global brain geometry may help predict dementia risk years before cognitive decline is noticeable.
Source: UC Irvine
Background: Researchers from the University of California, Irvine’s Center for the Neurobiology of Learning and Memory (CNLM), in collaboration with Universidad de La Laguna, used structural MRI to measure how the brain’s spatial anatomy changes across adult life. Their approach quantifies both global shape differences and distances between corresponding regions across hemispheres, revealing complex spatial patterns that traditional volume measures do not capture.
The study analyzed 2,603 structural MRI scans from adults aged 30 to 97. Findings show a clear pattern: inferior (lower) and anterior (front) brain regions tend to expand outward with age, while superior (upper) and posterior (back) regions trend inward. These asymmetric distortions were most pronounced in older adults with cognitive impairment and were replicated across independent datasets, strengthening the case that shape changes are a robust feature of aging.
Importantly, the magnitude and location of expansion or compression related to specific deficits. For example, greater posterior compression associated with poorer reasoning performance, indicating that geometric markers map onto real cognitive outcomes. The authors emphasize that these spatial patterns complement existing measures of regional tissue loss, offering a fuller picture of structural aging.
A particularly notable implication concerns the entorhinal cortex, a small but essential structure within the medial temporal lobe involved in memory. The study suggests that age-related shifts in brain geometry could push this fragile region closer to the rigid base of the skull, potentially exposing it to mechanical strain. Because the entorhinal cortex is an early site of tau accumulation in Alzheimer’s disease, the researchers propose that physical forces from shape change may help explain its selective vulnerability—an idea that expands current thinking about disease mechanisms.
“Most studies of brain aging focus on regional tissue loss,” said Niels Janssen, PhD, senior author and professor at Universidad de La Laguna and visiting faculty at CNLM. “We found that the brain’s overall shape shifts in consistent ways, and those shifts are closely tied to cognitive impairment.” Michael Yassa, PhD, CNLM director and study co-author, noted that gradual architectural changes could create conditions that make certain regions more susceptible to damage.
The authors propose that tracking global brain geometry could provide new biomarkers for dementia risk, enabling earlier identification of individuals on a path toward neurodegeneration. As the team continues to refine geometric metrics, these measures may become a useful complement to molecular and volumetric markers currently used in research and clinical settings.
The project was a joint effort between UC Irvine and Universidad de La Laguna. Co-first authors Yuritza Escalante and Jenna Adams, PhD, led the analytic work. Funding included support from the National Institute on Aging, part of the National Institutes of Health.
Key Questions Answered:
A: Aging alters both volume and global shape—some areas expand while others compress—producing geometric patterns linked to cognitive decline.
A: The geometry changes may create mechanical stress on regions like the entorhinal cortex, offering a potential explanation for why Alzheimer’s pathology arises there early.
A: Yes. Measuring global and regional shape changes could identify at-risk individuals years before symptoms appear and complement existing biomarkers.
About this Alzheimer’s disease research news
Author: Thomas Vasich
Source: UC Irvine
Contact: Thomas Vasich – UC Irvine
Image: Image credited to Neuroscience News
Original Research: Open access. DOI: 10.1038/s41467-025-63628-3
“Age-related constraints on the spatial geometry of the brain” by Niels Janssen et al., published in Nature Communications.
Abstract
Age-related constraints on the spatial geometry of the brain
Age-related structural brain changes may be better characterized by assessing complex spatial geometry rather than isolated regional differences. The authors applied an analytic method to quantify expansion and compression of global brain shape and to measure distances between homologous regions across hemispheres.
Analyzing 2,603 structural MRIs from adults aged 30–97, the study found that aging is associated with global expansion across inferior-anterior gradients, global compression across superior-posterior gradients, and regional expansion between frontotemporal homologues. Specific patterns of expansion and compression were linked to clinical impairment and distinct cognitive deficits.
These results suggest that alterations in the brain’s spatial anatomy and geometry are associated with reduced neural efficiency and cognitive dysfunction in older adults, highlighting the potential of geometric measures as biomarkers for early disease risk assessment.