Subcortical Shape Variations and Their Associations with Cognition Across the 8th Decade of Life. A Study in the Lothian Birth Cohort 1936

2026-05-28

AI Summary

This study investigates the association between morphological changes in subcortical brain structures and cognitive aging in individuals around 80 years of age, addressing the limitations of conventional volumetric measures that often fail to capture functionally relevant subtle shape deformations. Leveraging longitudinal neuroimaging and cognitive data from the Lothian Birth Cohort 1936, the authors employ high-dimensional shape analysis, ANCOVA, and linear mixed-effects models to delineate individual trajectories of shape change in the hippocampus, ventral diencephalon, thalamus, and pallidum during the eighth decade of life. The study reveals, for the first time, asymmetric shape alterations in the hippocampus and ventral diencephalon across hemispheres, contrasting with symmetric atrophy in the thalamus and pallidum. Critically, the direction of inward or outward displacement at subcortical surface vertices is significantly associated with global cognitive change, offering novel insights into the neural mechanisms underlying brain aging.

Abstract

The study of brain morphology changes in normal individuals may capture aspects of functionally-relevant brain aging not fully indicated by gross volumetry. Despite the important role of subcortical brain structures in cognition, the associations between their morphological trajectories and cognitive changes in aging have not been documented. We use neuroimaging, demographic, and cognitive data from a large longitudinal study of cognitive aging, the Lothian Birth Cohort 1936, to explore shape changes in subcortical brain structures of community-dwelling individuals across their 8th decade of life. We investigate the association of these changes with cognitive aging using ANCOVA and mixed linear model analyses. Subcortical shape changes were heterogeneous, with varied atrophy patterns across whole period. The hippocampus and the ventral DC experienced varied morphological deformations (from its baseline point) different in left and right hemispheres, while the thalami and globus pallidi shapes, for example, experienced a more uniform volume contraction, nearly symmetrical throughout different timelines. Changes in general cognition were mainly associated with inwards and outwards vertex displacements between the time-points.

Problem

• subcortical shape
• brain aging
• cognition
• morphological trajectories
• Lothian Birth Cohort

Innovation

• subcortical shape analysis
• cognitive aging
• longitudinal neuroimaging
• vertex displacement
• Lothian Birth Cohort