Working Memory related Frontal Brainwaves are Associated with pTau181Plasma Biomarkers in Healthy Older Adults.

Background: We have previously reported distinct frontal signature of working memory related potentials (WMRP) in older adults with Normal Cognition (NC) versus age‐matched older adults with Mild Cognitive Impairment (MCI) (Li et al., 2017; Fig 1A). Our Kentucky cohort demonstrates that asymptomatic older individuals with MCI‐like frontal brainwave patterns convert to MCI within a short 5‐year period, as opposed to individuals with NC‐like patterns that remain normal 10 years later (Jiang et al., 2021; Fig 1B). Leveraging blood‐based Vascular/AD biomarkers, we test the hypothesis that WMPR is associated with preclinical AD/ADRD pathologies. Method: 33 (19 women) cognitively intact older volunteers, average age 79 (SD 8.53) years old, from a longitudinal cohort followed by University of Kentucky ADRC participated. Each participant was assessed by electroencephalogram (EEG) recording (64‐ or 14‐channels headset) during a visual working memory task and vascular/AD plasma markers (Wilcock et al., 2022). Multiple linear regression analyses adjusting for age and sex were applied for examining several frontal WMRP difference waves (Target items held in working memory – Nontargets) and multiple vascular/AD plasma biomarkers Aβ 42/40, pTau181, and GFAP (astrocyte reactivity). Results: We examined the association between WMRP and the percentage changes of Aβ 42/40, pTau181, GFAP levels from plasma Vascular/AD biomarkers. The decrease of WMRP levels (MCI‐like) was significantly associated with increased level of pTau181 at the left frontal F7 site after adjusting for age and sex (b = ‐0.035 and p = 0.043) (Fig. 2). Aβ42/40 and GFAP levels were not significantly associated with working memory related brainwaves. Conclusion: Our results indicate that predictive WMRP are associated with tau pathologies. Working memory‐related EEG neuromarkers and plasma AD biomarkers are sensitive and affordable screening tools to predict continuous cognitive decline risk in healthy normal older adults. References Jiang, Y. et al. (2021). Memory‐Related Frontal Brainwaves Predict Transition to Mild Cognitive Impairment in Healthy Older Individuals Five Years Before Diagnosis. J. Alzheimer's Dis. 79, 531‐541. Li, J et al. (2017). A cognitive electrophysiological signature differentiates amnestic mild cognitive impairment from normal aging. Alzheimer's Res & Therapy, 9, 3. Wilcock D, et. al... (2021). MarkVCID cerebral small vessel consortium: I.Alzheimers Dement. 17:704‐715. [ABSTRACT FROM AUTHOR]