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Association of COVID‐19 Positivity with Biomarkers of Alzheimer's Disease and Cognitive Test Performance

Year: 2025

Type: article

Abstract: BACKGROUND: The amyloid cascade that causes Alzheimer's disease (AD) is associated in part with neuroinflammation, which may be affected by peripheral disease. COVID-19 has been implicated in cognitive change, though its effect on AD biomarkers is unclear. We leverage a cohort with biomarker and cognitive data pre- and post-COVID-pandemic to examine these relationships. METHOD: Data was obtained from the Wisconsin Registry for Alzheimer's Prevention (Table 1). Participants return biennially for cognitive and biomarker testing. We used the data from the most recent pre-pandemic visit, compared with the first post-pandemic visit, to examine biomarker and cognitive change. One-way ANOVA was used to examine annualized biomarker change as a function of both pTau217 positivity and participant-reported prior COVID test-positivity (pTau217-/COVID-; pTau217-/COVID+; pTau217+/COVID-; pTau217+/COVID+). Baseline-adjusted cognitive scores on tests measuring cognitive processes previously reported to be affected by COVID (trails B, animal naming, and letter fluency tests, memory and PACC-3 composite scores) were compared using two-tailed, unpaired t-tests (COVID- vs COVID+). RESULT: The pTau217+/COVID- group differed from both the pTau217-/COVID- and pTau217-/COVID+ groups, but these differences did not survive correction for multiple comparisons (Table 2). The biomarkers did not show any other significant differences between COVID+ and COVID- groups. The cognitive testing results trended towards the opposite relationship found in past studies, with those who were COVID+ averaging non-significantly higher percentile scores (Figure 1). Participants who tested positive for COVID-19 were more likely to be vaccinated, likely due to the increase in positive tests after vaccines were available. CONCLUSION: Overall, we did not find significant associations between COVID-19, cognitive test scores, or biomarker levels. Our data may be less robust given the high percentage of vaccinations among COVID-19 positive cases and that vaccination decreases infection severity. It is also possible that the slightly younger age of the COVID+ group acted as a confounding variable. Strengths of our study include comparison of individual biomarker data before and after the spread of COVID-19, interpretation of individual cognitive test scores relative to previous performance, and a large cohort size enriched with Alzheimer's disease risk factors.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz70856_102887