Generic placeholder image

当代阿耳茨海默病研究

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

炎症细胞因子在轻度认知障碍转化为痴呆中的作用:一项前瞻性研究

卷 19, 期 1, 2022

发表于: 27 January, 2022

页: [68 - 75] 页: 8

弟呕挨: 10.2174/1567205019666220127102640

价格: $65

Open Access Journals Promotions 2
摘要

背景:细胞因子对从轻度认知障碍 (MCI) 进展到持续性痴呆的影响是一个有争议的问题,迄今为止获得的结果是有争议的。 目的:本研究的目的是分析亚临床炎症标志物对 MCI 进展为痴呆的影响。 方法:进行了一项前瞻性研究,涉及一组年龄≥65 岁、被诊断为 MCI 并随访 3 年的患者。招募了 105 名患者,并测定了几种亚临床炎症标志物的血清浓度。 结果:经过 3.09 (2 - 3.79) 年的随访,47 名 (44.76%) 患者进展为痴呆。发现 Alpha 1-抗胰凝乳蛋白酶 (ACT) 在进展为痴呆的患者中显着升高(486.45 ± 169.18 vs. 400.91 ± 163.03;p = 0.012),并观察到显着增加轻度认知障碍患者患痴呆的风险(1.004, 1.001-1.007; p = 0.007)。那些保持稳定的人的 IL-10 水平显着更高(6.69 ± 18.1 vs. 32.54 ± 89.6;p = 0.04)。关于我们的患者进展到的痴呆类型,我们发现发生混合性痴呆的患者的 IL-4 水平高于转为 AD 的患者(31.54 ± 63.6 对 4.43 ± 12.9;p = 0.03)。在 ESR 和 LPa、CRP、IL-1 和 TNF-α 水平方面,各组之间没有观察到显着差异。 结论:ACT水平对MCI向痴呆的转化具有显着的预测价值。 IL-10 水平可能是一个保护因素。有必要对这些和其他炎症标志物进行系列测定,以确定它们对 MCI 进展为痴呆的影响。

关键词: α1-抗糜蛋白酶、抗炎细胞因子 IL-10、细胞因子、痴呆、炎症、轻度认知障碍、亚临床炎症。

[1]
World Health Organization, Alzheimer’s Disease International Dementia: A Public Health Priority. 2015. ISBN: 9789241564458.
[2]
Hou Y, Dan X, Babbar M, et al. Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 2019; 15(10): 565-81.
[http://dx.doi.org/10.1038/s41582-019-0244-7] [PMID: 31501588]
[3]
2020 Alzheimer´s disease facts and figures. Alzheimers Dement 2020. 16(3): 391-460.
[http://dx.doi.org/10.1002/alz.12068] [PMID: 32157811]
[4]
Ward A, Arrighi HM, Michels S, Cedarbaum JM. Mild cognitive impairment: disparity of incidence and prevalence estimates. Alzheimers Dement 2012; 8(1): 14-21.
[http://dx.doi.org/10.1016/j.jalz.2011.01.002] [PMID: 22265588]
[5]
Tangalos EG, Petersen RC. Mild cognitive impairment in geriatrics. Clin Geriatr Med 2018; 34(4): 563-89.
[http://dx.doi.org/10.1016/j.cger.2018.06.005] [PMID: 30336988]
[6]
Li L, Wang Y, Yan J, et al. Clinical predictors of cognitive decline in patients with mild cognitive impairment: the Chongqing aging study. J Neurol 2012; 259(7): 1303-11.
[http://dx.doi.org/10.1007/s00415-011-6342-0] [PMID: 22186849]
[7]
Nordlund A, Rolstad S, Klang O, Edman A, Hansen S, Wallin A. Two-year outcome of MCI subtypes and aetiologies in the Göteborg MCI study. J Neurol Neurosurg Psychiatry 2010; 81(5): 541-6.
[http://dx.doi.org/10.1136/jnnp.2008.171066] [PMID: 19965857]
[8]
Mitchell AJ, Monge-Argilés JA, Sánchez-Paya J. Do CSF biomarkers help clinicians predict the progression of mild cognitive impairment to dementia? Pract Neurol 2010; 10(4): 202-7.
[http://dx.doi.org/10.1136/jnnp.2010.217778] [PMID: 20647526]
[9]
Alexopoulos P, Grimmer T, Perneczky R, Domes G, Kurz A. Progression to dementia in clinical subtypes of mild cognitive impairment. Dement Geriatr Cogn Disord 2006; 22(1): 27-34.
[http://dx.doi.org/10.1159/000093101] [PMID: 16679762]
[10]
Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet 2006; 367(9518): 1262-70.
[http://dx.doi.org/10.1016/S0140-6736(06)68542-5] [PMID: 16631882]
[11]
Elias-Sonnenschein LS, Viechtbauer W, Ramakers IH, Verhey FR, Visser PJ. Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: a meta-analysis. J Neurol Neurosurg Psychiatry 2011; 82(10): 1149-56.
[http://dx.doi.org/10.1136/jnnp.2010.231555] [PMID: 21493755]
[12]
Gorelick PB. Risk factors for vascular dementia and Alzheimer disease. Stroke 2004; 35(11): 2620-2.
[http://dx.doi.org/10.1161/01.STR.0000143318.70292.47] [PMID: 15375299]
[13]
Cooper C, Sommerlad A, Lyketsos CG, Livingston G. Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis. Am J Psychiatry 2015; 172(4): 323-34.
[http://dx.doi.org/10.1176/appi.ajp.2014.14070878] [PMID: 25698435]
[14]
Kamat PK, Vacek JC, Kalani A, Tyagi N. Homocysteine induced cerebrovascular dysfunction: a link to Alzheimer’s disease etiology. Open Neurol J 2015; 9: 9-14.
[http://dx.doi.org/10.2174/1874205X01509010009] [PMID: 26157520]
[15]
Casado-Naranjo I, Romero Sevilla R, Portilla Cuenca JC, et al. Association between subclinical carotid atherosclerosis, hyperhomocysteinaemia and mild cognitive impairment. Acta Neurol Scand 2016; 134(2): 154-9.
[http://dx.doi.org/10.1111/ane.12525] [PMID: 26503595]
[16]
Wendell CR, Zonderman AB, Metter EJ, Najjar SS, Waldstein SR. Carotid intimal medial thickness predicts cognitive decline among adults without clinical vascular disease. Stroke 2009; 40(10): 3180-5.
[http://dx.doi.org/10.1161/STROKEAHA.109.557280] [PMID: 19644063]
[17]
Mazza M, Marano G, Traversi G, Bria P, Mazza S. Primary cerebral blood flow deficiency and Alzheimer’s disease: shadows and lights. J Alzheimers Dis 2011; 23(3): 375-89.
[http://dx.doi.org/10.3233/JAD-2010-090700] [PMID: 21098977]
[18]
Becher B, Spath S, Goverman J. Cytokine networks in neuroinflammation. Nat Rev Immunol 2017; 17(1): 49-59.
[http://dx.doi.org/10.1038/nri.2016.123] [PMID: 27916979]
[19]
Domingues C, da Cruz E Silva OAB, Henriques AG. Impact of cytokines and chemokines on Alzheimer’s disease neuropathological hallmarks. Curr Alzheimer Res 2017; 14(8): 870-82.
[http://dx.doi.org/10.2174/1567205014666170317113606] [PMID: 28317487]
[20]
Paouri E, Georgopoulos S. Systemic and CNS inflammation crosstalk: implications for Alzheimer’s disease. Curr Alzheimer Res 2019; 16(6): 559-74.
[http://dx.doi.org/10.2174/1567205016666190321154618] [PMID: 30907316]
[21]
Fakhoury M. Inflammation in Alzheimer’s disease. Curr Alzheimer Res 2020; 17(11): 959-61.
[http://dx.doi.org/10.2174/156720501711210101110513] [PMID: 33509069]
[22]
Friedberg JS, Aytan N, Cherry JD, et al. Associations between brain inflammatory profiles and human neuropathology are altered based on apolipoprotein E ε4 genotype. Sci Rep 2020; 10(1): 2924.
[http://dx.doi.org/10.1038/s41598-020-59869-5] [PMID: 32076055]
[23]
Abraham CR. Reactive astrocytes and alpha1-antichymotrypsin in Alzheimer’s disease. Neurobiol Aging 2001; 22(6): 931-6.
[http://dx.doi.org/10.1016/S0197-4580(01)00302-5] [PMID: 11755001]
[24]
Eriksson S, Janciauskiene S, Lannfelt L. Alpha 1-antichymotrypsin regulates Alzheimer beta-amyloid peptide fibril formation. Proc Natl Acad Sci USA 1995; 92(6): 2313-7.
[http://dx.doi.org/10.1073/pnas.92.6.2313] [PMID: 7892264]
[25]
Padmanabhan J, Levy M, Dickson DW, Potter H. Alpha1-antichymotrypsin, an inflammatory protein overexpressed in Alzheimer’s disease brain, induces tau phosphorylation in neurons. Brain 2006; 129(Pt 11): 3020-34.
[http://dx.doi.org/10.1093/brain/awl255] [PMID: 16987932]
[26]
Calsolaro V, Edison P. Neuroinflammation in Alzheimer’s disease: Current evidence and future directions. Alzheimers Dement 2016; 12(6): 719-32.
[http://dx.doi.org/10.1016/j.jalz.2016.02.010] [PMID: 27179961]
[27]
Hampel H, Caraci F, Cuello AC, et al. A path toward precision medicine for neuroinflammatory mechanisms in Alzheimer’s disease. Front Immunol 2020; 11: 456.
[http://dx.doi.org/10.3389/fimmu.2020.00456] [PMID: 32296418]
[28]
Swanson A, Wolf T, Sitzmann A, Willette AA. Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins. Behav Brain Res 2018; 347: 49-56.
[http://dx.doi.org/10.1016/j.bbr.2018.02.015] [PMID: 29462653]
[29]
Doecke JD, Laws SM, Faux NG, et al. Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol 2012; 69(10): 1318-25.
[http://dx.doi.org/10.1001/archneurol.2012.1282] [PMID: 22801742]
[30]
Soares HD, Potter WZ, Pickering E, et al. Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch Neurol 2012; 69(10): 1310-7.
[http://dx.doi.org/10.1001/archneurol.2012.1070] [PMID: 22801723]
[31]
Casado Naranjo I, Portilla Cuenca JC, Duque de San Juan B, et al. Association of vascular factors and amnestic mild cognitive impairment: a comprehensive approach. J Alzheimers Dis 2015; 44(2): 695-704.
[http://dx.doi.org/10.3233/JAD-141770] [PMID: 25362037]
[32]
Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004; 256(3): 240-6.
[http://dx.doi.org/10.1111/j.1365-2796.2004.01380.x] [PMID: 15324367]
[33]
Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation 2009; 120(16): 1640-5.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192644] [PMID: 19805654]
[34]
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3): 189-98.
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204]
[35]
Sheikh KH, Yesavage JA. Geriatric Depression Scale (GDS): recent evidence and development of a shorter version. Clin Gerontol 1986; 5: 165-73.
[http://dx.doi.org/10.1300/J018v05n01_09]
[36]
Pfeffer RI, Kurosaki TT, Harrah CH Jr, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol 1982; 37(3): 323-9.
[http://dx.doi.org/10.1093/geronj/37.3.323] [PMID: 7069156]
[37]
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. Washington, DC: American Psychiatric Association 1994.
[38]
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. Alzheimers Dement 2011; 7(3): 263-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
[39]
Román GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993; 43(2): 250-60.
[http://dx.doi.org/10.1212/WNL.43.2.250] [PMID: 8094895]
[40]
Rockwood K. Mixed dementia: Alzheimer’s and cerebrovascular disease. Int Psychogeriatr 2003; 15: 39-46.
[http://dx.doi.org/10.1017/S1041610203008949] [PMID: 16191215]
[41]
Kim JW, Stewart R, Kang HJ, et al. Longitudinal Associations Between Serum Cytokine Levels and Dementia. Front Psychiatry 2018; 9: 606.
[http://dx.doi.org/10.3389/fpsyt.2018.00606] [PMID: 30510525]
[42]
Licastro F, Parnetti L, Morini MC, et al. Acute phase reactant alpha 1-antichymotrypsin is increased in cerebrospinal fluid and serum of patients with probable Alzheimer disease. Alzheimer Dis Assoc Disord 1995; 9(2): 112-8.
[http://dx.doi.org/10.1097/00002093-199509020-00009] [PMID: 7662323]
[43]
Dik MG, Jonker C, Hack CE, Smit JH, Comijs HC, Eikelenboom P. Serum inflammatory proteins and cognitive decline in older persons. Neurology 2005; 64(8): 1371-7.
[http://dx.doi.org/10.1212/01.WNL.0000158281.08946.68] [PMID: 15851726]
[44]
DeKosky ST, Ikonomovic MD, Wang X, et al. Plasma and cerebrospinal fluid alpha1-antichymotrypsin levels in Alzheimer’s disease: correlation with cognitive impairment. Ann Neurol 2003; 53(1): 81-90.
[http://dx.doi.org/10.1002/ana.10414] [PMID: 12509851]
[45]
Brosseron F, Krauthausen M, Kummer M, Heneka MT. Body fluid cytokine levels in mild cognitive impairment and Alzheimer’s disease: a comparative overview. Mol Neurobiol 2014; 50(2): 534-44.
[http://dx.doi.org/10.1007/s12035-014-8657-1] [PMID: 24567119]
[46]
Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 2006; 12(9): 1005-15.
[PMID: 16960575]
[47]
King E, O’Brien JT, Donaghy P, et al. Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias. J Neurol Neurosurg Psychiatry 2018; 89(4): 339-45.
[http://dx.doi.org/10.1136/jnnp-2017-317134] [PMID: 29248892]
[48]
Sundelöf J, Kilander L, Helmersson J, et al. Systemic inflammation and the risk of Alzheimer’s disease and dementia: a prospective population-based study. J Alzheimers Dis 2009; 18(1): 79-87.
[http://dx.doi.org/10.3233/JAD-2009-1126] [PMID: 19542629]
[49]
Wichmann MA, Cruickshanks KJ, Carlsson CM, et al. Long-term systemic inflammation and cognitive impairment in a population-based cohort. J Am Geriatr Soc 2014; 62(9): 1683-91.
[http://dx.doi.org/10.1111/jgs.12994] [PMID: 25123210]
[50]
Koyama A, O’Brien J, Weuve J, Blacker D, Metti AL, Yaffe K. The role of peripheral inflammatory markers in dementia and Alzheimer’s disease: a meta-analysis. J Gerontol A Biol Sci Med Sci 2013; 68(4): 433-40.
[http://dx.doi.org/10.1093/gerona/gls187] [PMID: 22982688]
[51]
Bermejo P, Martín-Aragón S, Benedí J, et al. Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer’s disease. Immunol Lett 2008; 117(2): 198-202.
[http://dx.doi.org/10.1016/j.imlet.2008.02.002] [PMID: 18367253]
[52]
Darweesh SKL, Wolters FJ, Ikram MA, de Wolf F, Bos D, Hofman A. Inflammatory markers and the risk of dementia and Alzheimer’s disease: A meta-analysis. Alzheimers Dement 2018; 14(11): 1450-9.
[http://dx.doi.org/10.1016/j.jalz.2018.02.014] [PMID: 29605221]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy