Study on serum inflammatory factors and T lymphocyte subsets in Alzheimer's disease by repetitive transcranial magnetic stimulation combined with cognitive training
DONG Jingwen DU Yujie WANG Lixin CHEN Xiling
Department of Geriatrics,the Second Affiliated Hospital of Zhengzhou University,Henan Province,Zhengzhou 450014,China
Abstract:Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) combined with computerized cognitive training(CCT)on serum inflammatory factors and T lymphocyte subsets in Alzheimer's disease(AD).Methods A total of 76 patients with mild AD who met the inclusion criteria and treated in the Second Affiliated Hospital of Zhengzhou University from October 2020 to May 2022 were selected as the study objects.They were divided into treatment group and control group by random number method,with 38 patients in each group.Patients in the treatment group were treated with rTMS combined with CCT,and patients in the control group were treated with transcranial magnetic pseudo-stimulation combined with CCT.After treatment,the cognitive functions of the two groups were compared by the mini-mental state examination(MMSE)and the Alzheimer's disease assessment scale-cognition(ADAS-COG).The levels of interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ),killer T cells (TC),helper T cells (TH)and regulatory T cells (Tregs)before and after treatment were compared between the two groups.Results The levels of IL-6 and TNF-α in the treatment group were lower than those in the control group,and the differences were statistically significant(P<0.05).TH and Tregs levels in the treatment group were higher than those in the control group after treatment,and the differences were statistically significant(P<0.05).After treatment,the ADAS-COG score of the treatment group was lower than that of the control group,and the MMSE score was higher than that of the control group,with statistical significances (P<0.05).There were no significant differences in IFN-γ and TC levels between the two groups after treatment (P>0.05).After treatment,the levels of IL-6 and TNF-α in the treatment group were lower than those before treatment,and the level of IL-6 in the control group was lower than those before treatment,the differences were statistically significant (P<0.05).After treatment,TH and Tregs levels in the treatment group were higher than those before treatment,and the differences were statistically significant(P<0.05).After treatment,the ADAS-COG scores of both groups were lower than those before treatment,and the MMSE scores were higher than those before treatment,with statistical significances(P<0.05).Conclusion rTMS combined with CCT can reduce serum IL-6,TNF-α,increase serum TH,Tregs levels and improve cognitive function in AD patients.
董靖雯; 杜玉洁; 王理鑫; 陈淅泠. 重复经颅磁刺激联合认知训练对阿尔茨海默病患者血清炎症因子及T 淋巴细胞亚群的影响[J]. 中国当代医药, 2023, 30(21): 8-13.
DONG Jingwen DU Yujie WANG Lixin CHEN Xiling. Study on serum inflammatory factors and T lymphocyte subsets in Alzheimer's disease by repetitive transcranial magnetic stimulation combined with cognitive training. 中国当代医药, 2023, 30(21): 8-13.
Cao W,Zheng H.Peripheral immune system in aging and Alzheimer's disease[J].Mol Neurodegener,2018,13(1):51.
[2]
Luo L,Liu M,Fan Y,et al.Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFkappaB/NLRP3 signaling pathway in cerebral ischemic mice[J].J Neuroinflammation,2022,19(1):141.
[3]
Zong X,Dong Y,Li Y,et al.Beneficial Effects of Theta-Burst Transcranial Magnetic Stimulation on Stroke Injury via Improving Neuronal Microenvironment and Mitochondrial Integrity[J].Transl Stroke Res,2020,11(3):450-467.
[4]
Gates NJ,Vernooij RW,Di Nisio M,et al.Computerised cognitive training for preventing dementia in people with mild cognitive impairment[J].Cochrane Database Syst Rev,2019,3(3):D12279.
[5]
McKhann GM,Knopman DS,Chertkow H,et al.The diagnosis of dementia due to Alzheimer's disease:recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease[J].Alzheimers Dement,2011,7(3):263-269.
[6]
Folstein MF,Folstein SE,McHugh PR."Mini-mental state".A practical method for grading the cognitive state of patients for the clinician[J].J Psychiatr Res,1975,12(3):189-198.
[7]
Raghavan N,Samtani MN,Farnum M,et al.The ADAS-Cog revisited:novel composite scales based on ADAS-Cog to improve efficiency in MCI and early AD trials[J].Alzheimers Dement,2013,9(1 Suppl):S21-S31.
[8]
Jorfi M,Maaser-Hecker A,Tanzi RE.The neuroimmune axis of Alzheimer's disease[J].Genome Med,2023,15(1):6.
[9]
Hardy J,Selkoe DJ.The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics[J].Science,2002,297(5580):353-356.
[10]
Hong S,Beja-Glasser VF,Nfonoyim BM,et al.Complement and microglia mediate early synapse loss in Alzheimer mouse models[J].Science,2016,352(6286):712-716.
[11]
Sasso V,Bisicchia E,Latini L,et al.Repetitive transcranial magnetic stimulation reduces remote apoptotic cell death and inflammation after focal brain injury[J].J Neuroinflammation,2016,13(1):150.
[12]
Blumberger DM,Vila-Rodriguez F,Thorpe KE,et al.Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression(THREE-D):a randomised non-inferiority trial[J].Lancet,2018,391(10131):1683-1692.
[13]
Teti MJ,Masse C,Chopard G,et al.Repetitive Transcranial Magnetic Stimulation as an Add-On Treatment for Cognitive Impairment in Alzheimer's Disease and Its Impact on Self-Rated Quality of Life and Caregiver's Burden[J].Brain Sci,2021,11(6):740.
[14]
Pascual O,Ben AS,Rostaing P,et al.Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission[J].Proc Natl Acad Sci U S A,2012,109(4):E197-E205.
[15]
Gersner R,Kravetz E,Feil J,et al.Long-term effects of repetitive transcranial magnetic stimulation on markers for neuroplasticity:differential outcomes in anesthetized and awake animals[J].J Neurosci,2011,31(20):7521-7526.
[16]
Lenz M,Eichler A,Kruse P,et al.Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation[J].Front Immunol,2020,11:614509.
Luo J,Feng Y,Li M,et al.Repetitive Transcranial Magnetic Stimulation Improves Neurological Function and Promotes the Anti-inflammatory Polarization of Microglia in Ischemic Rats[J].Front Cell Neurosci,2022,16:878345.
[19]
Chitnis T,Weiner HL.CNS inflammation and neurodegeneration[J].J Clin Invest,2017,127(10):3577-3587.
[20]
Appel SH.CD4+T cells mediate cytotoxicity in neurodegenerative diseases[J].J Clin Invest,2009,119(1):13-15.
[21]
Huang X,Reynolds AD,Mosley RL,et al.CD4+T cells in the pathobiology of neurodegenerative disorders[J].J Neuroimmunol,2009,211(1-2):3-15.
[22]
Gate D,Saligrama N,Leventhal O,et al.Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease[J].Nature,2020,577(7790):399-404.
[23]
Raphael I,Nalawade S,Eagar TN,et al.T cell subsets and their signature cytokines in autoimmune and inflammatory diseases[J].Cytokine,2015,74(1):5-17.
[24]
Golubovskaya V,Wu L.Different Subsets of T Cells,Memory,Effector Functions,and CAR-T Immunotherapy[J].Cancers(Basel),2016,8(3):36.
[25]
Baruch K,Rosenzweig N,Kertser A,et al.Breaking immune tolerance by targeting Foxp3(+)regulatory T cells mitigates Alzheimer's disease pathology[J].Nat Commun,2015,6:7967.
[26]
Belleville S,Bherer L.Biomarkers of Cognitive Training Effects in Aging[J].Curr Transl Geriatr Exp Gerontol Rep,2012,1(2):104-110.