Login Register Cart 0
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Role of Inflammatory Cytokines in the Conversion of Mild Cognitive Impairment to Dementia: A Prospective Study

Author(s): Raúl Romero-Sevilla, Fidel López-Espuela, José Manuel Fuentes, Beatriz Duque de San Juan, Juan Carlos Portilla-Cuenca, Carmen Cámara Hijon and Ignacio Casado-Naranjo

Volume 19, Issue 1, 2022

Published on: 27 January, 2022

Page: [68 - 75] Pages: 8

DOI: 10.2174/1567205019666220127102640

Price: $65

Abstract

Background: The effect that cytokines can exert on the progression from mild cognitive impairment (MCI) to ongoing dementia is a matter of debate and the results obtained so far are controversial.

Objective: The aim of the study is to analyze the influence of markers of subclinical inflammation on the progression of MCI to dementia.

Methods: A prospective study involving a cohort of patients ≥ 65 years of age diagnosed with MCI and followed for 3 years was conducted. 105 patients were enrolled, and serum concentrations of several subclinical inflammatory markers were determined.

Results: After 3.09 (2 - 3.79) years of follow-up, 47 (44.76%) patients progressed to dementia. Alpha 1-antichymotrypsin (ACT) was found to be significantly higher in patients who progressed to dementia (486.45 ± 169.18 vs. 400.91 ± 163.03; p = 0.012), and observed to significantly increase the risk of developing dementia in patients with mild cognitive impairment (1.004, 1.001-1.007; p = 0.007). IL-10 levels were significantly higher in those who remained stable (6.69 ± 18.1 vs. 32.54 ± 89.6; p = 0.04). Regarding the type of dementia to which our patients progressed, we found that patients who developed mixed dementia had higher IL-4 levels than those who converted to AD (31.54 ± 63.6 vs. 4.43 ± 12.9; p = 0.03). No significant differences were observed between the groups with regard to the ESR and LPa, CRP, IL-1 and TNF-α levels.

Conclusion: ACT levels have a significant predictive value in the conversion of MCI to dementia. IL-10 levels could be a protective factor. It is necessary to conduct studies with serial determinations of these and other inflammatory markers in order to determine their effect on the progression of MCI to dementia.

Keywords: Alpha 1-antichymotrypsin, anti-inflammatory cytokines IL-10, cytokines, dementia, inflammation, mild cognitive impairment, subclinical inflammation.

« Previous Next »
[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
Article Metrics
39
1
© 2024 Bentham Science Publishers | Privacy Policy