Genetic Susceptibility to Multiple Sclerosis Impacts Memory in Young Adults
Multiple sclerosis (MS) is a complex neurodegenerative disease characterized by inflammation and demyelination of the central nervous system. In addition to motor and sensory deficits, MS often leads to cognitive impairments, including reduced working memory (WM). A recent study by J. Petrovska and colleagues explores the genetic underpinnings of MS and its association with WM performance in healthy young adults, using polygenic risk scores (PRS).
The research conducted by Petrovska et al. aimed to investigate the link between the polygenic risk for MS and WM performance in individuals aged 18-35. This study is significant as it focuses on a younger demographic, which may provide insights into the early genetic influences on cognitive functions related to MS. The researchers also explored the relationship between MS-PRS and brain white matter properties using fractional anisotropy (FA) measures.
The study involved 3282 healthy adults divided into two subsamples: Basel 1 (N=1803) and Basel 2 (N=1479). Participants performed a series of cognitive tasks, including a picture encoding task followed by a verbal n-back task, which is commonly used to assess WM. DNA samples were collected for genotyping, and PRSs were calculated using the latest GWAS data from the International Multiple Sclerosis Genetics Consortium (IMSGC).
Key Findings
Association with Working Memory: The study found a significant association between higher MS-PRS and lower WM performance in the lowest 10% of WM performers (p = 0.001; pFDR = 0.018). This suggests that individuals with a higher genetic predisposition to MS might exhibit poorer WM even before clinical symptoms manifest.
No Significant Association with FA: Despite the association with WM performance, MS-PRS did not show a significant correlation with FA measurements. This finding indicates that while MS genetic risk impacts cognitive function, it may not necessarily alter brain white matter properties in the same age group.
Implications
The results underscore the importance of genetic factors in cognitive functions associated with MS. Identifying genetic links between MS and cognitive deficits can enhance our understanding of the disease's pathophysiology and potentially lead to targeted interventions.
Limitations and Future Directions
The study acknowledges several limitations, including the skewed distribution of WM performance and the exclusive focus on individuals of European ancestry. Future research should aim to replicate these findings in larger, more diverse populations and explore whether these genetic associations persist across different cognitive tasks and age groups.
Conclusion
This pioneering study by Petrovska et al. highlights a crucial genetic link between MS susceptibility and WM performance in young adults. While the polygenic risk for MS impacts cognitive function, its influence on structural brain changes remains inconclusive. Continued research in this domain could pave the way for early diagnostic markers and tailored therapeutic strategies for cognitive impairments in MS.
References:
Petrovska, J., Coynel, D., Freytag, V., de Quervain, D. J. F., & Papassotiropoulos, A. (2024). Polygenic susceptibility for multiple sclerosis is associated with working memory in low-performing young adults. medRxiv, 2024-03.
