Selective Effects of Healthy Cognitive Aging and Catechol- O -Methyl Transferase Polymorphism on Limbic White Matter Tracts

Abstract

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 (COMT) gene polymorphism on the DTI measurements of these white matter tracts.

Methods:

We recruited 140 healthy participants (18–85 years old). DTI data sets were acquired on a 1.5T magnetic resonance imaging system. The 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 (C_l ), planar (C_p ), and spherical (C_s ) 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 C_s values in the right rostral cingulum compared with the valine carriers across the entire adult life span.

Discussion:

This study indicates that limbic tracts might be nonuniformly affected by healthy aging, and the methionine homozygous genotype might be associated with micro/macro white matter properties of the right rostral cingulum.

Impact statement

To better understand pathological age-related changes of brain's tracts, understanding normal age-related changes and its contributing factors including genetic polymorphisms are fundamental. To do so, we studied the associations between age and catechol-O-methyl transferase (COMT) polymorphism with structural properties of uncinate fasciculus and cingulum segments in a large cohort of healthy adults using deterministic tractography and fractional polynomial regression. Our results suggested that aging nonuniformly affects limbic tracts. Furthermore, in accordance with the major role of COMT in prefrontal cortex function, our findings indicated that COMT polymorphism was associated with white matter properties of the right rostral cingulum.