Peripheral Blood Regulatory T Cells and IL-6 are Associated with Cognitive Impairment After Acute Ischemic Stroke

Yueyue Chang,1,2 Xuke Zhang,3 Chuanqing Yu,2 Lei Zhu,1 Shiyu Sun,2 Zhongwu Sun1 1Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Neurology, The First Hospital of Anhui University of Science & Technology (Huainan First People’s Hospital), Huainan, 232000, People’s Republic of China; 3Department of Neurology, Bengbu Medical College, Bengbu, 241000, People’s Republic of ChinaCorrespondence: Zhongwu Sun, Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email sunzhwu@126.comBackground: Abstract Objective: Regulatory T cells (Tregs) and interleukin (IL)-6 are known to be involved in the progression of cognitive impairment but the association with post-stroke cognitive impairment remains little studied. Levels of Tregs and IL-6 in peripheral blood serum of patients with acute ischemic stroke (AIS) were investigated to assess the association with post-stroke cognitive impairment (PSCI).Methods: A total of 256 AIS patients were enrolled with 19 lost to follow-up after six months. Participants were divided into those without post-stroke cognitive impairment (PSNCI, n=129) and those with post-stroke cognitive impairment (PSCI, n=108). PSCI patients were subdivided into those with post-stroke cognitive impairment, no dementia (PSCIND, n=87) and those with post-stroke dementia (PSD, n=21). The percentage of peripheral blood CD4+ CD25+ CD127 (low) regulatory T cells (Tregs%) out of total CD4+ lymphocytes was evaluated by flow cytometry. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA).Results: (1) Increased percentages of peripheral blood Tregs and IL-6 levels were found in PSCI, PSCIND and PSD patients relative to PSNCI and differences were particularly significant for PSCI and PSD groups. (2) Logistic regression analysis was performed after controlling for these risk factors and Tregs% (OR=1.122, 95% CI: 1.006– 1.251, p=0.038) identified as an independent risk factor for cognitive impairment after AIS. ROC analysis gave an area under the curve (AUC) of 0.763 (95% CI: 0.653– 0.873) for the combination of Tregs% and IL-6 levels in predicting cognitive impairment after AIS.(3) IL-6 level (OR=1.307, 95% CI: 1.058– 1.614, p=0.013) was found to be an independent risk factor for dementia after AIS with an AUC of 0.805 (95% CI: 0.681– 0.929).Conclusion: Elevated peripheral Tregs% and IL-6 levels are risk factors for cognitive impairment after AIS. Their combined predictive power is greater than individual predictive power, exposing new therapeutic targets for post-stroke cognitive impairment.Keywords: acute ischemic stroke, post-stroke cognitive impairment, post-stroke dementia, Tregs, IL-6