Hakinya Karra, Varsha S Penumalee, Shreya Arun, Sanjana Javalkar, Genila Bibat, Matthew Ridder, Aaron J Kaat, Mathula Thangarajh
More than 80% of health outcomes are determined by social determinants of health. That social determinants of health affect physical health outcomes, as shown in previous studies of Duchenne muscular dystrophy, a progressive X-linked recessive genetic disease caused by variants in the DMD gene, in which males are affected whereas females are disease carriers. To date, however, whether community-level disadvantage affects brain health in Duchenne muscular dystrophy has not been investigated. We addressed this question by measuring cognitive performance of 65 males with Duchenne muscular dystrophy and their 60 biological mothers recruited from a national pool of study participants, hypothesizing that community disadvantage would negatively correlate with cognitive performance. The social vulnerability index-a geospatially determined scale-was used to estimate the degree of community disadvantage experienced by each son-mother dyad using their residential zip code. Total, crystallized, and fluid composite cognition scores were obtained from all study participants using an age-appropriate battery of cognition with the National Institutes of Health Toolbox Cognition Battery. The location of Duchenne muscular dystrophy variants from affected Duchenne muscular dystrophy males and the Duchenne muscular dystrophy carrier status of their biological mothers were collected as part of the study protocol. The mean age of the 65 males with Duchenne muscular dystrophy was 10.7 years [standard deviation 3.6], and their 60 biological mothers were 42.0 years [standard deviation 7.0]. Males with Duchenne muscular dystrophy scored lower than age-expected norms in fluid cognition (n = 57, mean = 82.7; standard deviation = 22.8), and within age-expected range in crystallized and total cognition (n = 56, mean = 105.4, standard deviation = 21.3; n = 55, mean = 93.5, standard deviation = 24.9, respectively). As a group, biological mothers scored in the normative range, except in one fluid cognition measure, namely the Flanker task of inhibitory control and attention. Biological mothers who were DMD carriers scored lower than non-carrier mothers in total composite and fluid cognition scores. Among the fluid cognition scores, DMD carriers scored lower in the Flanker task of inhibitory control and attention and cognitive flexibility. Son-mother dyads from communities with higher social vulnerability index scored lower on fluid cognition measures, namely the Flanker task of inhibitory control and attention (r = -0.20) and the dimensional card change sort test of cognitive flexibility (r = -0.16), respectively. Males with Duchenne muscular dystrophy and their biological mothers from disadvantaged communities demonstrate vulnerability in cognitive measures that are critical for attention regulation and cognitive flexibility. Our data highlighted the influence of the experiential social environment in Duchenne muscular dystrophy.