Plasma Phosphorylated-tau181 Is a Predictor of Post-stroke Cognitive Impairment: A Longitudinal Study

Li-Kai Huang; Shu-Ping Chao; Chaur-Jong Hu; Li-Nien Chien; Hung-Yi Chiou; Yu-Chun Lo; Yi-Chen Hsieh

doi:10.3389/fnagi.2022.889101

Plasma Phosphorylated-tau181 Is a Predictor of Post-stroke Cognitive Impairment: A Longitudinal Study

Front Aging Neurosci. 2022 Apr 29:14:889101. doi: 10.3389/fnagi.2022.889101. eCollection 2022.

Authors

Li-Kai Huang^{1

2

3

4

5}, Shu-Ping Chao^{1

2

4}, Chaur-Jong Hu^{1

2

4

6

7}, Li-Nien Chien^{8

9

10}, Hung-Yi Chiou^{11

12

13}, Yu-Chun Lo⁷, Yi-Chen Hsieh^{7

12

14}

Affiliations

¹ Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
² Dementia Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
³ Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan.
⁵ Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.
⁶ Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁸ Graduate Institution of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan.
⁹ School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan.
¹⁰ Health Data Analytics and Statistics Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan.
¹¹ Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
¹² Master Program in Applied Epidemiology, College of Public Health, Taipei Medical University, Taipei, Taiwan.
¹³ School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
¹⁴ Ph.D. Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.

Abstract

Introduction: Post-stroke cognitive impairment (PSCI) cannot be neglected because it drastically influences the daily life of patients and their families. However, there are no studies exploring the association between preclinical blood biomarkers of neurodegeneration including plasma amyloid-β (Aβ), tau, and brain-derived neurotrophic factor (BDNF) together with the risk of PSCI. This longitudinal study was to investigate whether these blood biomarkers with imaging markers of cerebral small vessel disease can improve the prediction for PSCI. In addition, we also explored the association between blood biomarkers with the trajectories of PSCI.

Methods: Adult patients with first-ever acute ischemic stroke were recruited, and the cognitive and functional abilities of these patients were evaluated. Furthermore, blood biomarkers of neurodegeneration including plasma Aβ-40, Aβ-42, total tau, phosphorylated tau 181 (p-tau181), and BDNF levels and image markers of cerebral small vessel disease were measured. Each patient was followed up at 3 and 12 months at the outpatient department.

Results: Of 136 patients, 40 and 50 patients developed PSCI at 3 and 12 months after stroke, respectively. In functional trajectories, 27 patients did not have PSCI at 3 months but did at 12 months. By contrast, the PSCI status of 17 patients at 3 months was reversed at 12 months. Patients with high-acute plasma p-tau181 had a significantly lower PSCI risk at 3 months (odds ratio [OR] = 0.62, 95% CI = 0.40-0.94, p = 0.0243) and 12 months (OR = 0.69, 95% CI = 0.47-0.99, p = 0.0443) after adjustment for covariates and image biomarkers. Discrimination and reclassification statistics indicated that the p-tau181 level can improve discrimination ability for PSCI at 3 and 12 months, respectively. In addition, the plasma p-tau181 level was the highest in subjects without PSCI followed by those with delayed-onset PSCI and early-onset PSCI with reversal, whereas the lowest plasma p-tau181 level was found among those with persistent PSCI, showing a significant trend test (p = 0.0081).

Conclusion: Plasma p-tau181 is a potential biomarker for predicting early- and delayed-onset PSCI. Future studies should incorporate plasma p-tau181 as an indicator for timely cognitive intervention in the follow-up of patients with stroke.

Keywords: biomarker; delayed-onset PSCI; early-onset PSCI; ischemic stroke; p-tau181.