Donepezil Hydrochloride Ameliorates Peripheral Inflammation in Vascular Dementia by Regulating Treg Homeostasis. Sai Qi
Description
Background: Vascular dementia (VD) is the second most common type of dementia after Alzheimer's disease, with complex pathology and high prevalence. Donepezil hydrochloride, a classic acetylcholinesterase inhibitor, has been clinically shown to improve cognitive function in VD patients. Recent studies suggest it also possesses neuroprotective and anti-inflammatory properties. Peripheral inflammation and immune dysregulation can drive neuroinflammation and cognitive impairment. Regulatory T cells (Tregs) are crucial for maintaining immune homeostasis and preventing excessive inflammation. Decreased Treg number and function have been linked to cognitive impairment in VD. However, it remains unclear whether donepezil alleviates cognitive deficits in VD by modulating peripheral Treg homeostasis and reducing peripheral inflammation. Methods: 70 patients with VD were recruited and assigned to the donepezil group, while 70 normal elderly individuals were recruited and assigned to the normal control group. Both groups underwent neurobehavioral scale testing, flow cytometry, and enzyme-linked immunosorbent assay, and correlation analysis was conducted on the test results of patients with VD. Results: Donepezil hydrochloride ameliorated cognitive impairment in VD patients, reduced apoptosis of peripheral blood lymphocyte subsets (Annexin V CD4+ and Annexin V CD8+ T cells), increases in the proportions of peripheral blood(CD3+ and CD4+ T cells, Tregs, Ki67+CD3+, Ki67+CD4+ and Ki67+CD8+ T cells, Ki67+Tregs, as well as the CD4+/CD8+ T-cell ratio). Furthermore, it decreased pro-inflammatory cytokines (IL-1β, TNF-α), and elevated anti-inflammatory cytokines (IL-2, IL-4, IL-10, IL-35, TGF-β1) in the peripheral blood. In VD patients, a strong negative correlation existed between changes in ADAS-cog scores and the proportion of Tregs. Changes in the proportion of CD4+ T cells showed a strong negative correlation with that of CD8+ T cells and a positive correlation with that of Tregs. Change in the proportion of Tregs exhibited a strong positive correlation with changes in IL-10, IL-35, and TGF-β1 levels. Conclusions: It was found that the improvement of cognitive ability in patients with VD by donepezil hydrochloride may be closely related to the increase in the proportion and function of Tregs and the reduction in peripheral inflammation levels.
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70 patients with VD were recruited and assigned to the donepezil group, while 70 normal elderly individuals were recruited and assigned to the normal control group. Both groups underwent neurobehavioral scale testing, flow cytometry, and enzyme-linked immunosorbent assay, and correlation analysis was conducted on the test results of patients with VD.
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- Yunnan Province Science and Technology DepartmentChinaGrant ID: Grant No. 202201AU070176, 202301AZ070001-026