Table 3_Potential association between dementia polygenic risk scores and subjective cognitive burden in a post-COVID cohort: a hypothesis-generating study.xlsx

Associations between PRS and cognitive scores were examined using Spearman’s rank correlation. All analyses were considered exploratory because no independent validation cohort was available.</p>Results<p>COVID-19–affected individuals aged 18–52 years showed a modest rightward shift in dementia-related PRS compared with population reference samples, with substantial overlap between groups (mean standardized PRS 0.24 vs. − 0.01; Mann–Whitney U = 29,504.5, p = 0.065; Cohen’s d = 0.25).

Memory-related difficulties contributed most strongly to the shared variance across cognitive domains, with PC1 explaining 52.5% of the variance. Among the 15 participants with cognitive assessment, PRS showed a positive but uncertain association with subjective cognitive burden (Spearman’s r = 0.51, 95% CI − 0.02 to 0.82, p = 0.054).</p>Conclusion<p>This hypothesis-generating study identified a possible relationship between dementia-related genetic liability and subjective cognitive burden after COVID-19.

The PRS group comparison was descriptive and should not be interpreted as evidence of increased dementia risk. The phenotype–genotype finding is severely limited by the small subgroup, possible selection bias, non-validated subjective assessment, lack of multivariable adjustment, and cross-sectional design. Validation in larger, ancestry-matched, longitudinal cohorts is required.</p>