Medicine and Health Sciences Commons^™

A Polygenic Risk Score Derived From Episodic Memory Weighted Genetic Variants Is Associated With Cognitive Decline In Preclinical Alzheimer’S Disease, Tenielle Porter, Samantha C. Burnham, Greg Savage, Yen Ying Lim, Paul Maruff, Lidija Milicic, Madeline Peretti, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, Kevin Taddei, David Groth, Guiseppe Verdile, Victor L. Villemagne, Simon M. Laws

Research outputs 2014 to 2021

Studies of Alzheimer’s disease risk-weighted polygenic risk scores (PRSs) for cognitive performance have reported inconsistent associations. This inconsistency is particularly evident when PRSs are assessed independent of APOE genotype. As such, the development and assessment of phenotype-specific weightings to derive PRSs for cognitive decline in preclinical AD is warranted. To this end a episodic memory-weighted PRS (emPRS) was derived and assessed against decline in cognitive performance in 226 healthy cognitively normal older adults with high brain Aβ-amyloid burden participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. The effect size for decline in a verbal episodic memory …