Abstract
The aging brain undergoes a cascade of structural changes — subcortical volumes shrink, functional connectivity networks reorganize, and the boundary between gray and white matter becomes less distinct. These changes are measurable on MRI and are often assumed to track with cognitive decline, but the relationship is more complex than it appears. Not all structural changes predict functional impairment equally, and some individuals show substantial anatomical change with little cognitive consequence, while others decline cognitively with relatively preserved structure. Understanding which specific brain changes are most predictive of future cognitive outcomes — and in whom — is essential for developing neuroimaging-based screening tools.
This project focuses on three complementary dimensions of brain structure in healthy older adults, using longitudinal data from the UK Biobank. First, we examined the association between changes in subcortical volume and longitudinal cognitive measures, asking whether volume loss in specific subcortical structures (hippocampus, amygdala, thalamus, caudate) predicts cognitive trajectories more reliably than global atrophy measures. Second, we investigated how changes in functional connectivity relate to cognitive function over time, testing whether network-level reorganization carries prognostic information beyond what structural measures provide.
Third, and perhaps most novel, we are analyzing gray-white matter contrast (GWC) — a metric that captures the sharpness of the boundary between cortical gray matter and underlying white matter. GWC is sensitive to subtle changes in myelination and cortical microstructure that volumetric measures may miss entirely. We are characterizing GWC changes in healthy adults over time, identifying predictors and patterns that differentiate individuals whose GWC increases (potentially reflecting compensatory myelination) from those in whom it declines (potentially reflecting early degeneration). This study is in preparation for GeroScience.
Together, these studies aim to build a multi-dimensional picture of how the aging brain changes and which dimensions of change matter most for predicting who will remain cognitively healthy and who will not.