Role of Polygenic Risk Scores in Predicting Cognitive Functioning after Mild Traumatic Brain Injury: A TRACK-TBI...

Area of Science:

• Neuroscience
• Genetics
• Traumatic Brain Injury Research

Background:

• Mild traumatic brain injury (mTBI) commonly leads to cognitive deficits, including issues with processing speed, memory, and executive functions.
• Understanding genetic predispositions may offer insights into individual differences in cognitive outcomes post-mTBI.
• Polygenic risk scores (PRS) are emerging tools to assess genetic contributions to complex traits like cognition.

Purpose of the Study:

• To investigate the prognostic value of four PRS for cognitive outcomes at 6 months following mTBI.
• To determine if PRS for educational attainment, intelligence, and Alzheimer's disease predict cognitive function after mTBI.
• To explore the role of cognitive reserve in mTBI recovery using genetic and educational factors.

Main Methods:

• A prospective study of 523 individuals of European descent treated for mTBI at a U.S. level 1 trauma center.
• Assessment of cognitive outcomes using z-scores relative to predicted pre-injury performance at 6 months post-mTBI.
• Analysis of four PRS: Education-PRS, Intelligence-PRS, AD-PRS (APOE), and AD + APOE-PRS, controlling for demographic and clinical factors.

Main Results:

• Education-PRS and Intelligence-PRS showed initial associations with all cognitive outcomes.
• After controlling for covariates, Education-PRS and Intelligence-PRS independently predicted verbal episodic memory.
• Associations with processing speed and executive functioning were largely mediated by educational attainment, suggesting a cognitive reserve effect.

Conclusions:

• PRS for education and intelligence offer modest predictive value for specific cognitive outcomes, particularly verbal memory, after mTBI.
• Educational attainment plays a significant role in mediating the effects of these PRS on cognitive recovery, supporting cognitive reserve theories.
• PRS may serve as a valuable, albeit small, addition to multivariable models for predicting cognitive function post-TBI.