Prediction of Episodic Memory With Multiomics Scores.

Background: Episodic memory (EM) refers to the ability to encode and recall events-a vital cognitive function for healthy cognitive aging and an endophenotype for dementia. Methods: Using genome- and metabolome-wide least absolute shrinkage and selection operator (LASSO) analysis, we developed polygenic (LASSO-PRS) and metabolic risk scores (MRS) in ∼68.5-year-old individuals (n = 897). We also applied the Bayesian regression method PRS-CS to an external genome-wide meta-analysis (GWAMA, N = 29,785, age > 18 years) to derive another PRS (GWAMA-PRS). We assessed incremental variances (R 2) in EM explained by the PRSs and MRS separately and in combination beyond the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score in 104 independent ∼68.5-year-old individuals. Finally, we validated the PRSs in 2 independent pediatric cohorts (N = 309, age = ∼11.9 years; N = 443, age = ∼8.6 years). Results: In the independent sample of ∼68.5-year-old individuals, compared with CAIDE score alone, accounting additionally for either MRS, LASSO-PRS, or GWAMA-PRS increased R 2 by 1.6, 5.6, and 4.5 percentage points (pp), respectively, while accounting additionally for MRS + LASSO-PRS or MRS + GWAMA-PRS increased R 2 by 7.8 and 6.4 pp, respectively. Both LASSO-PRS (all false discovery rate [FDR]-adjusted p values = .01-.03) and GWAMA-PRS (all FDR-adjusted p values = .03) were significantly associated with EM in all models, while the CAIDE score and MRS were not (all FDR-adjusted p values > .05). PRSs were not associated with EM in the pediatric cohorts (all FDR-adjusted p values > .05). Conclusions: Genomics added predictive value to EM beyond epidemiological risk factors in adults, but the same was not observed with metabolomics. Adult-derived PRSs did not predict EM in children.