Selective effects of healthy cognitive aging and Catechol-O-methyl transferase (COMT) polymorphism on limbic white matter tracts.

INTRODUCTION The cingulum bundle and uncinate fasciculus are major limbic white matter tracts involved in emotion, memory, and cognition. The main goal of the present study was to investigate the relationship between age and structural properties of the uncinate fasciculus and the cingulum bundle using diffusion tensor imaging (DTI) tractography in a large cohort of healthy individuals. The second goal was to determine the effects of the Catechol-O-methyl transferase gene (COMT) polymorphism on the DTI measurements of these white matter tracts. METHODS We recruited 140 healthy participants (18-85 years old). DTI datasets were acquired on a 1.5 T MRI system. Rostral, dorsal, and parahippocampal cingulum, as well as uncinate fasciculus, were delineated using deterministic tractography. Fractional anisotropy (FA), mean (MD), radial (RD), and axial (AD) diffusivities, tract volume, linear (Cl), planar (Cp), and spherical (Cs) tensor shapes were calculated. The COMT polymorphism (methionine homozygous vs. valine carriers) was determined using single nucleotide polymorphism. RESULTS We found that age was negatively associated with FA, but positively associated with MD, and RD for the rostral cingulum, dorsal cingulum, and the uncinate fasciculus but not for the parahippocampal cingulum. Furthermore, individuals with the COMT methionine homozygous had higher FA and lower MD, RD, AD, and Cs values in the right rostral cingulum compared to the valine carriers across the entire adult life span. DISCUSSION This study indicates that limbic tracts might be non-uniformly affected by healthy aging and the methionine homozygous genotype might be associated with micro/macro white matter properties of the right rostral cingulum.