Aging Brain Reveals Hidden Patterns of Geometric Restructuring Linked to Cognitive Decline

In a significant departure from traditional models of brain aging, new research reveals that aging is not only marked by shrinking brain volume but also by a profound reorganization of the brain’s spatial geometry—changes that are tightly linked to cognitive decline.

Published in Nature Communications, the study introduces a novel approach to studying brain aging that goes beyond the typical focus on isolated regions or volume loss. Instead, researchers analyzed how the brain’s shape morphs over time by measuring geometric shifts—specifically, global expansion and compression of brain structures and changes in the distances between corresponding regions across the brain's hemispheres.

The findings are the result of an extensive analysis of over 2,600 structural MRI scans from adults aged 30 to 97 years, drawn from two major datasets: the Open Access Series of Imaging Studies (OASIS) and the Cambridge Centre for Ageing and Neuroscience (Cam-CAN).

Contrary to the idea that aging leads uniformly to brain shrinkage, the study reveals a spatially complex pattern: global expansion in inferior-anterior regions of the brain—including parts of the frontal and temporal lobes—and compression in superior-posterior areas, such as the parietal and occipital cortices.

These geometric changes appear early in the aging process and progressively intensify with age. By using a fine-grained grid of 400 cortical surface points, researchers calculated Euclidean distances between corresponding locations in the brain’s two hemispheres. The result: a vivid map of how brain shape shifts with age—not just in size, but in structure and spatial configuration.

Crucially, the study linked these geometric alterations to cognitive performance and clinical impairment. Older adults with clinical signs of cognitive decline (as measured by the Clinical Dementia Rating) showed a reversed pattern compared to healthy aging: compression in frontal regions and expansion in posterior areas, suggesting that deviations from typical geometric aging patterns may serve as early indicators of pathology.

Further analyses revealed that different cognitive domains are associated with distinct patterns of brain shape change. Poor episodic memory, for example, was related to anterior expansion and posterior compression, especially in temporal lobe regions critical for memory processing. In contrast, executive function impairments were tied to compression in parietal regions, and working memory decline was linked to lateral compression in the parietal, temporal, and frontal cortices.

Notably, the greatest age-related expansions in interhemispheric distances were found in subcortical regions—such as the caudate, thalamus, and amygdala—and medial temporal areas like the hippocampus and entorhinal cortex. These regions are already known to be vulnerable to atrophy in Alzheimer’s disease and other neurodegenerative conditions, underscoring the clinical significance of geometric distortions in these structures.

The researchers argue that these geometric brain changes may constrain the brain’s ability to function efficiently, potentially disrupting communication across regions and contributing to age-related cognitive decline. They also propose that tracking these changes using standard MRI could enhance early detection of neurodegenerative disorders.