Introduction: Although high cerebral white matter hyperintensity volume (WMHv) is associated with cognitive decline, many adults with high WMHv show no cognitive deficits. Neurodegenerative plasma biomarkers may be associated with cognitive decline via vascular processes causing higher WMHv such as cerebral amyloid angiopathy & inflammatory small vessel disease. We determined associations of plasma amyloid β 42 (AB42), amyloid β 40 (AB40), AB42/AB40, total tau, & neurofilament light chain (NfL) with cognitive resilience (CR) in adults with high WMHv using baseline MRIs & measurements from SPRINT MIND. Methods: This study included baseline data from 186 SPRINT MIND participants who were in the highest WMHv tertile & had available plasma biomarker concentrations & Montreal Cognitive Assessment (MoCA) scores. We defined CR two ways: A) MoCA score >25 or B) MoCA score >22. We determined univariate & adjusted odds ratios (OR) & 90% confidence intervals (CI) for each aforementioned plasma biomarker with CR. Confounders in adjusted models were: age, sex, race-ethnicity (Non-Hispanic white, Non-Hispanic Black, Hispanic, or other) education (no college education, college education, or post-graduate education), smoking history (never smoker, prior smoker, or current smoker) physical activity (0, 1-4, or ≥ 5 days of vigorous physical activity), diabetes, having insurance, & average systolic blood pressure. Residual confounding and effect modification by WMHv were tested in sensitivity analyses. Results: In our sample, the mean age was 72.6 years, 45.7% were female & 66% were Non-Hispanic white. The median WMHv was 10.0 cm 3 (25%-75% range: 6.3 - 16.9 cm 3 ). . CR defined as MoCA scores > 25 & >22 was present in 28.5% & 56.5% of participants respectively. Lower plasma AB40 was marginally associated with CR using a MoCa cutoff of >25 (OR 1.003, 90% CI: 1.001-1.006) in univariate analyses. There were no other significant (P>0.1) univariate or adjusted associations between plasma biomarkers with CR using either MoCa cutoff, nor significant confounding or effect modification by WMHv (P> 0.1). Conclusion: There were no significant adjusted associations between any plasma biomarker with CR. Future work should identify factors associated with CR in adults with high WMHv.
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