Cognitive Capacity Genome-Wide Polygenic Scores Identify Individuals with Slower Cognitive Decline in Aging

The genetic protective factors for cognitive decline in aging remain unknown. Predicting an individual's rate of cognitive decline-or with better cognitive resilience-using genetics will allow personalized intervention for cognitive enhancement and the optimal selection of target samples in clinical trials. Here, using genome-wide polygenic scores (GPS) of cognitive capacity as the genomic indicators for variations of human intelligence, we analyzed the 18-year records of cognitive and behavioral data of 8511 European-ancestry adults from the Wisconsin Longitudinal Study (WLS), specifically focusing on the cognitive assessments that were repeatedly administered to the participants with their average ages of 64.5 and 71.5. We identified a significant interaction effect between age and cognitive capacity GPS, which indicated that a higher cognitive capacity GPS significantly correlated with a slower cognitive decline in the domain of immediate memory recall (β = 1.86 × 10^-1, p-value = 1.79 × 10^-3). The additional phenome-wide analyses identified several associations between cognitive capacity GPSs and cognitive/behavioral phenotypes, such as similarities task (β = 1.36, 95% CI = (1.22, 1.51), p-value = 3.59 × 10^-74), number series task (β = 0.94, 95% CI = (0.85, 1.04), p-value = 2.55 × 10^-78), IQ scores (β = 1.42, 95% CI = (1.32, 1.51), p-value = 7.74 × 10^-179), high school classrank (β = 1.86, 95% CI = (1.69, 2.02), p-value = 3.07 × 10^-101), Openness from the BIG 5 personality factor (p-value = 2.19 × 10^-14, β = 0.57, 95% CI = (0.42, 0.71)), and leisure activity of reading books (β = 0.50, 95% CI = (0.40, 0.60), p-value = 2.03 × 10^-21), attending cultural events, such as concerts, plays, or museums (β = 0.60, 95% CI = (0.49, 0.72), p-value = 2.06 × 10^-23), and watching TV (β = -0.48, 95% CI = (-0.59, -0.37), p-value = 4.16 × 10^-18). As the first phenome-wide analysis of cognitive and behavioral phenotypes, this study presents the novel genetic protective effects of cognitive ability on the decline of memory recall in an aging population.