Association Between Inflammatory Markers and Cognitive Impairment in Patients with Asymptomatic Carotid Stenosis

Authors

  • Elena Joveva Faculty of Medical Sciences, University Goce Delcev, Stip, North Macedonia; Clinical Hospital of Stip, Stip, North Macedonia image/svg+xml https://orcid.org/0000-0001-9659-1535
  • Marija Karakolevska-Ilova Faculty of Medical Sciences, University Goce Delcev, Stip, North Macedonia; Clinical Hospital of Stip, Stip, North Macedonia image/svg+xml https://orcid.org/0000-0001-7353-2110
  • Marijan Jovev Faculty of Medical Sciences, University Goce Delcev, Stip, North Macedonia; Clinical Hospital of Stip, Stip, North Macedonia
  • Stefan Petrovski Faculty of Medical Sciences, University Goce Delcev, Stip, North Macedonia; Clinical Hospital of Stip, Stip, North Macedonia image/svg+xml
  • Aleksandar Serafimov Faculty of Medical Sciences, University Goce Delcev, Stip, North Macedonia; Clinical Hospital of Stip, Stip, North Macedonia https://orcid.org/0000-0003-3638-1397
  • Marija Dimitrovska-Ivanova Faculty of Medical Sciences, University Goce Delcev, Stip, North Macedonia; Clinical Hospital of Stip, Stip, North Macedonia image/svg+xml https://orcid.org/0000-0001-8641-6979

DOI:

https://doi.org/10.3889/oamjms.2024.11851

Keywords:

carotid stenosis, inflammatory markers, cognitive impairment

Abstract

BACKGROUND: Certain inflammatory mechanisms are involved in the carotid atherosclerotic process, and determining the inflammatory activation can be useful in the assessment of cognitive impairment in patients with asymptomatic carotid stenosis (ACS).

AIM: This study aimed to correlate these markers of inflammation with the degree of asymptomatic carotid stenosis (ACS) and the degree of cognitive impairment.

MATERIALS AND METHODS: One hundred and twenty patients with carotid stenosis and 60 patients without carotid stenosis were enrolled in the study. Clinical, neurological, and laboratory evaluations (C-reactive protein [CRP], fibrinogen, tumor necrosis factor alpha [TNF-α]) were performed, as well as evaluation of intima-media thickness (IMT) and carotid stenosis degree. Cognitive functions were assessed with the Addenbrooke’s Cognitive Examination test. Neuroimaging tests were included.

RESULTS: There was no significant correlation in the asymptomatic group between TNFα and IMT and between fibrinogen, CRP, and IMT both on the left and the right side. In the same group, there was a statistically significant association between the degree of carotid stenosis and low-to-moderate degree of cognitive impairment on the right side (p < 0.05) and left side (p < 0.05). A moderately weak negative statistically significant correlation between the severity of cognitive impairment and the degree of stenosis in the asymptomatic group was reported. A high degree of carotid stenosis (≥70%) on the right increased the chance of a moderate degree of cognitive impairment by 6 times compared to the low degree of carotid stenosis in the asymptomatic group. The high degree of carotid stenosis (≥70%) on the left increased the chance of a severe degree of cognitive impairment by 20 times compared to the low degree of stenosis in the asymptomatic group.

CONCLUSIONS: ACS increases the risk of cognitive impairment.

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References

Hofman A, Ott A, Breteler MM, Bots ML, Slooter AJ, Van Harskamp F, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet. 1997;349(9046):151-4. https://doi.org/10.1016/S0140-6736(96)09328-2 PMid:9111537 DOI: https://doi.org/10.1016/S0140-6736(96)09328-2

Johnston SC, O’Meara ES, Manolio TA, Lefkowitz D, O’Leary DH, Goldstein S, et al. Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Internal Med. 2004;140(4):237-47. https://doi.org/10.7326/0003-4819-140-4-200402170-0000 PMid:14970146 DOI: https://doi.org/10.7326/0003-4819-140-4-200402170-00005

Mathiesen EB, Waterloo K, Joakimsen O, Bakke SJ, Jacobsen EA, Bonaa KH. Reduced neuropsychological test performance in asymptomatic carotid stenosis: The tromso study. Neurology. 2004;62(5):695-701. https://doi.org/10.1212/01.wnl.0000113759.80877.1f PMid:15007116 DOI: https://doi.org/10.1212/01.WNL.0000113759.80877.1F

Pettigrew LC, Thomas N, Howard VJ, Veltkamp R, Toole JF. Low mini-mental status predicts mortality in asymptomatic carotid arterial stenosis. Asymptomatic carotid atherosclerosis study investigators. Neurology. 2000;55(1):30-4. https://doi.org/10.1212/wnl.55.1.30 PMid:10891899 DOI: https://doi.org/10.1212/WNL.55.1.30

Sabeti S, Exner M, Mlekusch W, Amighi J, Quehenberger P, Rumpold H, et al. Prognostic impact of fibrinogen in carotid atherosclerosis: Nonspecific indicator of inflammation or independent predictor of disease progression? Stroke. 2005;36(7):1400-4. https://doi.org/10.1161/01.STR.0000169931.96670.fc PMid:15933258 DOI: https://doi.org/10.1161/01.STR.0000169931.96670.fc

Elkind M, Cheng J, Albala B, Paik M, Sacco R. Elevated white blood cell count and carotid plaque thickness. The Northern Manhattan stroke study. Stroke. 2001;32(4):842-9. https://doi.org/10.1161/01.str.32.4.842 PMid:11283380 DOI: https://doi.org/10.1161/01.STR.32.4.842

Assayag EB, Bova I, Kesler A, Berliner S, Shapira I, Bornstein NM. Erythrocyte aggregation as an early biomarker in patients with asymptomatic carotid stenosis. Dis Markers. 2008;24(1):33-9. https://doi.org/10.1155/2008/184647 PMid:18057534 DOI: https://doi.org/10.1155/2008/184647

Garcia BA, Ruiz C, Chacon P, Sabin JA, Matas M. High-sensitivity C-reactive protein in high-grade carotid stenosis: Risk marker for unstable carotid plaque. J Vasc Surg. 2003;38(5):1018-24. https://doi.org/10.5114/aoms.2013.34533 PMid:14603210 DOI: https://doi.org/10.1016/S0741-5214(03)00709-2

Kablak-Ziembicka A, Przewlocki T, Sokołowski A, Tracz W, Podolec P. Carotid intima-media thickness, hs-CRP and TNF-α are independently associated with cardiovascular event risk in patients with atherosclerotic occlusive disease. Atherosclerosis. 2011;214(1):185-90. https://doi.org/10.1016/j.atherosclerosis.2010.10.017 PMid:21067752 DOI: https://doi.org/10.1016/j.atherosclerosis.2010.10.017

Bond MG, Barnes RW, Riley WA, Wilmoth SK, Chambless LE, Howard G, Owens B, The ARIC Study Group. High-resolution B-mode ultrasound scanning methods in the Atherosclerosis Risk in Communities study (ARIC). J Neuroimag 1991;1:68-73. PMid:10149810 DOI: https://doi.org/10.1111/jon19911268

Larner AJ, Mitchell AJ. A meta-analysis of the accuracy of the Addenbrooke’s cognitive examination (ACE) and the Addenbrooke’s cognitive examination-revised (ACE-R) in the detection of dementia. Int Psychogeriatr. 2014;26(4):555-63. https://doi.org/10.1017/S1041610213002329 PMid:24423470 DOI: https://doi.org/10.1017/S1041610213002329

Kwah LK, Diong J. National institutes of health stroke scale (NIHSS). J Physiother. 2014;60(1):61. https://doi.org/10.1016/j.jphys.2013.12.012 PMid:24856948 DOI: https://doi.org/10.1016/j.jphys.2013.12.012

Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340(2):115-26. https://doi.org/10.1056/NEJM199901143400207 PMid: 9887164 DOI: https://doi.org/10.1056/NEJM199901143400207

Pelisek J, Rudelius M, Zepper P, Poppert H, Reeps C, Schuster T, et al. Multiple biological predictors for vulnerable carotid lesions. Cerebrovasc Dis. 2009;28(6):601-10. https://doi.org/10.1159/000247605 PMid:19844101 DOI: https://doi.org/10.1159/000247605

Nishida H, Horio T, Suzuki Y, Iwashima Y, Tokudome T, Yoshihara F, et al. Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: Comparison with C-reactive protein. Cytokine. 2011;53(3):342-6. https://doi.org/10.1016/j.cyto.2010.12.005 PMid:21190868 DOI: https://doi.org/10.1016/j.cyto.2010.12.005

Mallat Z, Besnard S, Duriez M, Deleuze V, Emmanuel F, Bureau MF, et al. Protective role of interleukin-10 in atherosclerosis. Circ Res. 1999;85(8):e17-24. https://doi.org/10.1161/01.res.85.8.e17 PMid:10521249 DOI: https://doi.org/10.1161/01.RES.85.8.e17

Koutouzis M, Rallidis LS, Peros G, Nomikos A, Tzavara V, Barbatis C, et al. Serum interleukin-6 is elevated in symptomatic carotid bifurcation disease. Acta Neurol Scand. 2009;119(2):119-25. https://doi.org/10.1111/j.1600-0404.2008.01068.x PMid:18638042 DOI: https://doi.org/10.1111/j.1600-0404.2008.01068.x

Zhang L, Pappel K, Sivashanmugam P, Orman ES, Brian L, Exum ST, et al. Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27(5):1087-94. https://doi.org/10.1161/ATVBAHA.0000261548.49790.63 PMid:17442899 DOI: https://doi.org/10.1161/01.ATV.0000261548.49790.63

Huber SA, Sakkinen P, Conze D, Hardin N, Tracy R. Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscl Thromb Vasc Biol. 1999;19(10):2364-7. https://doi.org/10.1161/01.ATV.19.10.2364 PMid:10521365 DOI: https://doi.org/10.1161/01.ATV.19.10.2364

Elkind MS, Cheng J, Boden-Albala B, Rundek T, Thomas J, Chen H, et al. Tumor necrosis factor receptor levels are associated with carotid atherosclerosis. Stroke. 2002;33(1):31-7. https://doi.org/10.1161/hs0102.100531 PMid:11779885 DOI: https://doi.org/10.1161/hs0102.100531

Kyriakidis K, Antoniadis P, Choksy S, Papi RM. Comparative study of protein expression levels of five plaque biomarkers and relation with carotid plaque type classification in patients after carotid endarterectomy. Int J Vasc Med. 2018;2018:4305781. https://doi.org/10.1155/2018/4305781 PMid:30581625 DOI: https://doi.org/10.1155/2018/4305781

Pearson TA, Mensah GA, Alexander WR, Anderson JL, Cannon RO, Criqui M, et al. Markers of inflammation and cerebrovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from centers for disease control and prevention and the American heart association. Circulation. 2003;107(3):499-511. https://doi.org/10.1161/01.cir.0000052939.59093.45 PMid:12551878 DOI: https://doi.org/10.1161/01.CIR.0000052939.59093.45

Ridker PM, Morrow DA. C-reactive protein, inflammation, and coronary risk. Cardiol Clin. 2003;21(3):315-25. https://doi.org/10.1016/s0733-8651(03)00079-1. PMID: 14621448. DOI: https://doi.org/10.1016/S0733-8651(03)00079-1

Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the predication of cardiovascular disease in women. N Engl J Med. 2000;342(12):836- 43. https://doi.org/10.1056/NEJM200003233421202 PMid:10733371 DOI: https://doi.org/10.1056/NEJM200003233421202

Bruno D, Vignaga SS. Addenbrooke’s cognitive examination III in the diagnosis of dementia: A critical review. Neuropsychiatr Dis Treat. 2019;15:441-7. https://doi.org/10.2147/NDT.S151253 PMid:30858702 DOI: https://doi.org/10.2147/NDT.S151253

Panegyres PK, Berry R, Burchell J. Early dementia screening. Diagnostics (Basel). 2016;6(1):6. https://doi.org/10.3390/diagnostics6010006 PMid:26838803 DOI: https://doi.org/10.3390/diagnostics6010006

Fiedorova D, Krulova P, Ressner P, Jaremova V, Slonkova J, Bar M, Skoloudik D, et al. Addenbrooke’s cognitive examination in nondemented patients after stroke. Neuropsychiatry. 2018;8(2):505-12. DOI: https://doi.org/10.4172/Neuropsychiatry.1000372

Lees RA, Hendry Ba K, Broomfield N, Stott D, Larner AJ, Quinn TJ. Cognitive assessment in stroke: Feasibility and test properties using differing approaches to scoring of incomplete items. Int J Geriatr Psychiatry. 2017;32(10):1072-8. https://doi.org/10.1002/gps.4568 PMid:27526678 DOI: https://doi.org/10.1002/gps.4568

Engelter ST, Gostynski M, Papa S, Frei M, Born C, Ajdacic-Gross V, et al. Epidemiology of aphasia attributable to first ischemic stroke: Incidence, severity, fluency, etiology, and thrombolysis. Stroke. 2006;37(6):1379-84. https://doi.org/10.1161/01.STR.0000221815.64093.8c PMid:16690899 DOI: https://doi.org/10.1161/01.STR.0000221815.64093.8c

Lal BK, Dux MC, Sikdar S, Goldstein C, Khan AA, Yokemick J, et al. Asymptomatic carotid stenosis is associated with cognitive impairment. J Vasc Surg. 2017;66(4):1083-92. https://doi.org/10.1016/j.jvs.2017.04.038 PMid:28712815 DOI: https://doi.org/10.1016/j.jvs.2017.04.038

Rostamian S, Mahinrad S, Stijnen T, Sabayan B, De Craen AJ. Cognitive impairment and risk of stroke: A systematic review аnd meta-analysis of prospective cohort studies. Stroke. 2014;45(5):1342-8. https://doi.org/10.1161/STROKEAHA.114.004658 PMid:24676778 DOI: https://doi.org/10.1161/STROKEAHA.114.004658

Arntzen KA, Schirmer H, Johnsen SH, Wilsgaard T, Mathiesen EB. Carotid atherosclerosis predicts lower cognitive test results: A 7-year follow-up study of 4,371 stroke-free subjects. The Tromsø study Cerebrovasc Dis. 2012;33(3):159-65. https://doi.org/10.1159/000334182 PMid:22222422 DOI: https://doi.org/10.1159/000334182

Romero JR, Beiser A, Seshadri S, Benjamin EJ, Polak JF, Vasan RS, et al. Carotid artery atherosclerosis, MRI indices of brain ischemia, aging and cognitive impairment: The Framingham study. Stroke. 2009;40(5):1590-6. https://doi.org/10.1161/strokeaha.108.535245 PMid:19265054 DOI: https://doi.org/10.1161/STROKEAHA.108.535245

Martinić-Popović I, Lovrenčić-Huzjan A, Demarin V. Advanced asymptomatic carotid disease and cognitive impairment: An understated link? Stroke Res Treat. 2012;2012:981416. https://doi.org/10.1155/2012/981416 PMid:22577604 DOI: https://doi.org/10.1155/2012/981416

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Published

2024-03-20

How to Cite

1.
Joveva E, Karakolevska-Ilova M, Jovev M, Petrovski S, Serafimov A, Dimitrovska-Ivanova M. Association Between Inflammatory Markers and Cognitive Impairment in Patients with Asymptomatic Carotid Stenosis. Open Access Maced J Med Sci [Internet]. 2024 Mar. 20 [cited 2024 May 26];12:1-8. Available from: https://oamjms.eu/index.php/mjms/article/view/11851

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