Thalamus anatomy predicts cognitive performance and hippocampal atrophy in aging adults: a UK Biobank study

The thalamus has extensive inter-connectedness with different brain regions in serving cognitive processes. In a community-dwelling aging population from the United Kingdom, this study examined the independent contribution of thalamus volume loss to cognitive performances and the longitudinal anatomical relationship between the thalamus and the interconnected hippocampus. We accessed MRI data from 4348 cognitively unimpaired older adults from the UK Biobank, of whom 653 participants had follow-up MRI. We estimated regional brain volumes using T1-weighted MRI. Linear models tested the association between the thalamus volume and a cognitive composite score derived from digit-symbol substitution and trail-making tests. We used latent change score models to test the longitudinal associations between thalamus volume at baseline and the trajectory of hippocampal atrophy, and vice versa. Baseline thalamus volume was positively associated with the cognitive composite score ( $\beta =0.055\pm 0.018$ , P = 0.002, R ² = 0.09). A larger baseline thalamus volume predicted slower hippocampal atrophy ( ${\gamma }_{T\to \mathrm{dH}}=-0.048\pm 0.015,P=0.001,R^2=0.09$ ), while larger hippocampal volume at baseline predicted faster thalamic atrophy ( ${\gamma }_{H\to dT}=0.043\pm 0.022,P=0.048,R^2=0.04$ ). Sex-stratified analysis revealed that hippocampal volume significantly predicted thalamic atrophy only in women. This study revealed that thalamic volume loss was associated with impaired processing speed and executive function. Thalamus and hippocampus anatomy showed bidirectional longitudinal associations and demonstrated sex differences. These findings underscore the thalamus anatomy as an important marker of brain health in the aging population.