Cross-Sectional Gender Comparison of Gray Matter Concentration in Prodromal Huntington’s Disease

Georgia State University, Atlanta, Georgia, 30303, University of Iowa, Iowa City, Iowa , 52242

Huntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal repetition of the cytosine-adenine-guanine (CAG) trinucleotide in the HTT gene. This polyglutamine mutation causes behavioral, cognitive, and motor abnormalities such as chorea. Additionally, HD is characterized by striatal atrophy prior to symptom onset. This experiment investigated gender contributions in pre-diagnosed or prodromal HD stages as well as striatal effect on motor dysfunction. All prodromal HD participants were positive for the genetic mutation. This cross- sectional study correlated striatal volume between men and women at different stages of prodromal HD. It was expected to see greater gender differences with increasing prodromal HD stages due to past HD gender studies. Structural Magnetic Resonance (sMRI) data were collected from more than a thousand cans and decomposed into specific regions via independent component analysis. Regions within the striatum became gray matter profiles of interest. Statistical analyses were conducted to quantify a relationship between gender and stage as well as striatal effect on motor dysfunction. Gender did not correlate with striatal volume at different prodromal stages yet striatal volume correlated with motor abnormalities as expected. Additionally, striatal volume decreased with increasing prHD stages. The results supported previous findings associating striatal volume and prHD stages, yet gender contributions were not identified. A study limitation is the use of a cross sectional analysis; interactions between gender and rate of striatal atrophy have yet to be studied longitudinally in a prodromal HD cohort. Indexing prodromal progression factors could enhance therapeutic targets by isolating the earliest-affected regions of the brain in both sexes, which is vital for future treatment.

Ogbu et al 2020.pdf1.07 MB