Doctor of Philosophy
Date of Defense
Rob Paul, PhD
Lisa Dorner, Ph.D.
Oxidative stress is a key mechanism of the aging process that can cause damage to brain white matter and cognitive functions. Allele variations of two polymorphisms (SOD2, CAT -262) have been associated with abnormalities in antioxidant enzyme activity, suggesting a risk for enhanced oxidative damage to brain white matter and cognition among older individuals with these genetic mutations. The present study utilized diffusion tensor imaging (DTI) and neuropsychological assessment to compare differences in microstructural white matter integrity and cognitive performance among 96 older adults (age 50-85) with and without genetic risk factors of SOD2 (rs4880) and CAT -262 (rs1001179). Results revealed significantly higher radial diffusivity (RD) in the anterior thalamic radiation (ATR) among CC genotypes of SOD2 compared to CT/TT genotypes. Further, the CC genotype significantly moderated the relationship between the hippocampal segment of the cingulum (CHC) and processing speed. Neither CAT-262, nor the combined effect of SOD2 and CAT-262 risk alleles were significantly associated with brain outcomes in this cohort. Collectively these results suggest that the CC genotype of SOD2 is an important genetic marker of suboptimal brain aging in this cohort of otherwise healthy older adults.
Salminen, Lauren, "Genetic risk for increased oxidative stress in the aging brain:Implications for white matter integrity and cognition" (2016). Dissertations. 61.