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Published in: Clinical Rheumatology 5/2020

01-05-2020 | Systemic Sclerosis | Original Article

Evaluation of cognitive function in systemic sclerosis patients: a pilot study

Authors: Eman M. Khedr, Noha Abo El Fetoh, Rania M. Gamal, Mona H. Elzohri, Nashwa Mostafa A. Azoz, Daniel E. Furst

Published in: Clinical Rheumatology | Issue 5/2020

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Abstract

Objective

To investigate cognitive dysfunction in adult patients with systemic sclerosis (SSc) who had no known clinical neurological manifestations and to relate it with other disease severity parameters.

Methods

In the present study, 20 SSc consecutive female patients, who met the 2013 American College of Rheumatology SSc criteria, were compared with 20 healthy age–, gender-, and educational status–matched volunteer hospital workers. Mean age and duration of illness were 41.8 ± 12.52 and 6.9 ± 5.4 years respectively. Mini-Mental State Examination (MMSE), Wechsler Adult Intelligence scale (WAIS-III), and P300 component of event-related potentials (ERPs) were used to evaluate cognitive function in SS subjectively and objectively respectively.

Results

Sixty-five percent (13 out of 20) of SSc patients had MMSE score < 25, and cognitive impairment. Despite the lack of clinically apparent neurological manifestations, SSc patients had significantly low MMSE score, high Deterioration Index (DI), and prolonged P300 latency compared with that of the control group (P = 0.0001; 0.010 and 0.008 respectively). A significant positive association was found between (DI) and the Medsger severity vascular score (r = 0.518; P = 0.012).There were few differences between limited and diffuse SSc.

Conclusions

To our knowledge, few studies highlighted that subclinical cognitive impairment can occur in the course of SSc disease. Early diagnosis of cognitive impairment should be investigated either subjectively (using psychometrics tests as MMSE or WAIS-III) or objectively using P300 evoked related potentials. Medsger severity vascular score seems to be closely related to cognitive impairment.
Key points
• Cognitive impairment can be associated with Medsger Vascular severity score and the duration of illness.
• Further larger studies will be needed to estimate the effect of disease activity on cognitive function, to further delineate the differences between limited and diffuse SSc in this area, and to understand the underlying pathophysiological mechanisms causing cognitive impairment in patients with SSc.
• To investigate impaired cognitive function in patients with SSc, even in the absence of clinically apparent neurological and vascular disease.
Literature
3.
go back to reference Zhong W, Cruickshanks KJ, Schubert CR, Acher CW, Carlsson CM, Klein BE, Klein R, Chappell RJ (2012) Carotid atherosclerosis and 10-year changes in cognitive function. Atherosclerosis 224(2):506–510PubMedPubMedCentralCrossRef Zhong W, Cruickshanks KJ, Schubert CR, Acher CW, Carlsson CM, Klein BE, Klein R, Chappell RJ (2012) Carotid atherosclerosis and 10-year changes in cognitive function. Atherosclerosis 224(2):506–510PubMedPubMedCentralCrossRef
4.
go back to reference Silvestrini M, Gobbi B, Pasqualetti P, Bartolini M, Baruffaldi R, Lanciotti C, Cerqua R, Altamura C, Provinciali L, Vernieri F (2009) Carotid atherosclerosis and cognitive decline in patients with Alzheimer’s disease. Neurobiol Aging 30(8):1177–1183PubMedCrossRef Silvestrini M, Gobbi B, Pasqualetti P, Bartolini M, Baruffaldi R, Lanciotti C, Cerqua R, Altamura C, Provinciali L, Vernieri F (2009) Carotid atherosclerosis and cognitive decline in patients with Alzheimer’s disease. Neurobiol Aging 30(8):1177–1183PubMedCrossRef
5.
go back to reference Gatto NM, Henderson VW, St. John JA, McCleary C, Detrano R, Hodis HN, Mack WJ (2009) Subclinical atherosclerosis is weakly associated with lower cognitive function in healthy hyperhomocysteinemic adults without clinical cardiovascular disease. Int J Geriatr Psychiatry 24(4):390–399PubMedPubMedCentralCrossRef Gatto NM, Henderson VW, St. John JA, McCleary C, Detrano R, Hodis HN, Mack WJ (2009) Subclinical atherosclerosis is weakly associated with lower cognitive function in healthy hyperhomocysteinemic adults without clinical cardiovascular disease. Int J Geriatr Psychiatry 24(4):390–399PubMedPubMedCentralCrossRef
6.
go back to reference Gamal RM, Gamal WM, Ghandour AM, Abozaid HSM, Mohamed ME, Emad Y, Abdel Galeel A (2018) Study of the osteoprotegerin/receptor activator of nuclear factor-kB ligand system association with inflammation and atherosclerosis in systemic sclerosis. Immunol Investig 47(3):241–250CrossRef Gamal RM, Gamal WM, Ghandour AM, Abozaid HSM, Mohamed ME, Emad Y, Abdel Galeel A (2018) Study of the osteoprotegerin/receptor activator of nuclear factor-kB ligand system association with inflammation and atherosclerosis in systemic sclerosis. Immunol Investig 47(3):241–250CrossRef
7.
go back to reference Khedr EM, El Fetoh NA, Herdan O, El-Hammady DH, Khalifa H, Gamal RM, Ali AM (2015) Clinical and subclinical neuropsychiatric abnormalities in rheumatoid arthritis patients. Egypt Rheumatol Rehabil 42(1):11CrossRef Khedr EM, El Fetoh NA, Herdan O, El-Hammady DH, Khalifa H, Gamal RM, Ali AM (2015) Clinical and subclinical neuropsychiatric abnormalities in rheumatoid arthritis patients. Egypt Rheumatol Rehabil 42(1):11CrossRef
8.
go back to reference Khedr EM, Khedr T, Farweez HM, Abdella G, El Beih EA (2001) Multimodal electroneurophysiological studies of systemic lupus erythematosus. Neuropsychobiology 43(3):204–212PubMedCrossRef Khedr EM, Khedr T, Farweez HM, Abdella G, El Beih EA (2001) Multimodal electroneurophysiological studies of systemic lupus erythematosus. Neuropsychobiology 43(3):204–212PubMedCrossRef
9.
go back to reference Monastero R, Bettini P, Del Zotto E, Cottini E, Tincani A, Balestrieri G, Cattaneo R, Camarda R, Vignolo LA, Padovani A (2001) Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations. J Neurol Sci 184(1):33–39PubMedCrossRef Monastero R, Bettini P, Del Zotto E, Cottini E, Tincani A, Balestrieri G, Cattaneo R, Camarda R, Vignolo LA, Padovani A (2001) Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations. J Neurol Sci 184(1):33–39PubMedCrossRef
10.
go back to reference Tomietto P, Annese V, D’agostini S, Venturini P, La Torre G, De Vita S, Ferraccioli G (2007) General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Care Res 57(8):1461–1472CrossRef Tomietto P, Annese V, D’agostini S, Venturini P, La Torre G, De Vita S, Ferraccioli G (2007) General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Care Res 57(8):1461–1472CrossRef
11.
go back to reference Bertinotti L, Mortilla M, Conforti ML, Colangelo N, Nacci F, Del Rosso A, Fonda C, Casale R, Matucci-Cerinic M, Pignone A (2006) Proton magnetic resonance spectroscopy reveals central neuroaxonal impairment in systemic sclerosis. J Rheumatol 33(3):546–551PubMed Bertinotti L, Mortilla M, Conforti ML, Colangelo N, Nacci F, Del Rosso A, Fonda C, Casale R, Matucci-Cerinic M, Pignone A (2006) Proton magnetic resonance spectroscopy reveals central neuroaxonal impairment in systemic sclerosis. J Rheumatol 33(3):546–551PubMed
17.
go back to reference Mattsson M, Bostrom C, Mihai C, Stocker J, Geyh S, Stummvoll G, Gard G, Moller B, Hesselstrand R, Sandqvist G, Draghicescu O, Gherghe AM, Voicu M, Distler O, Smolen JS, Stamm TA (2015) Personal factors in systemic sclerosis and their coverage by patient-reported outcome measures. A multicentre European qualitative study and literature review. Eur J Phys Rehabil Med 51(4):405–421PubMed Mattsson M, Bostrom C, Mihai C, Stocker J, Geyh S, Stummvoll G, Gard G, Moller B, Hesselstrand R, Sandqvist G, Draghicescu O, Gherghe AM, Voicu M, Distler O, Smolen JS, Stamm TA (2015) Personal factors in systemic sclerosis and their coverage by patient-reported outcome measures. A multicentre European qualitative study and literature review. Eur J Phys Rehabil Med 51(4):405–421PubMed
18.
go back to reference Suarez-Almazor ME, Kallen MA, Roundtree AK, Mayes M (2007) Disease and symptom burden in systemic sclerosis: a patient perspective. J Rheumatol 34(8):1718–1726PubMed Suarez-Almazor ME, Kallen MA, Roundtree AK, Mayes M (2007) Disease and symptom burden in systemic sclerosis: a patient perspective. J Rheumatol 34(8):1718–1726PubMed
20.
go back to reference Khanna D, Distler O, Avouac J, Behrens F, Clements PJ, Denton C, Foeldvari I, Giannini E, Huscher D, Kowal-Bielecka O, Lovell D, Matucci-Cerinic M, Mayes M, Merkel PA, Nash P, Opitz CF, Pittrow D, Rubin L, Seibold JR, Steen V, Strand CV, Tugwell PS, Varga J, Zink A, Furst DE (2009) Measures of response in clinical trials of systemic sclerosis: the Combined Response Index for Systemic Sclerosis (CRISS) and Outcome Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis (EPOSS). J Rheumatol 36(10):2356–2361. https://doi.org/10.3899/jrheum.090372 PubMedCrossRef Khanna D, Distler O, Avouac J, Behrens F, Clements PJ, Denton C, Foeldvari I, Giannini E, Huscher D, Kowal-Bielecka O, Lovell D, Matucci-Cerinic M, Mayes M, Merkel PA, Nash P, Opitz CF, Pittrow D, Rubin L, Seibold JR, Steen V, Strand CV, Tugwell PS, Varga J, Zink A, Furst DE (2009) Measures of response in clinical trials of systemic sclerosis: the Combined Response Index for Systemic Sclerosis (CRISS) and Outcome Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis (EPOSS). J Rheumatol 36(10):2356–2361. https://​doi.​org/​10.​3899/​jrheum.​090372 PubMedCrossRef
23.
go back to reference Pauling JD, Frech TM, Domsic RT, Hudson M (2017) Patient participation in patient-reported outcome instrument development in systemic sclerosis. Clin Exp Rheumatol 35 Suppl 106(4):184–192 Pauling JD, Frech TM, Domsic RT, Hudson M (2017) Patient participation in patient-reported outcome instrument development in systemic sclerosis. Clin Exp Rheumatol 35 Suppl 106(4):184–192
24.
go back to reference Medsger TA Jr, Bombardieri S, Czirjak L, Scorza R, Della Rossa A, Bencivelli W (2003) Assessment of disease severity and prognosis. Clin Exp Rheumatol 21(3 Suppl 29):S42–S46PubMed Medsger TA Jr, Bombardieri S, Czirjak L, Scorza R, Della Rossa A, Bencivelli W (2003) Assessment of disease severity and prognosis. Clin Exp Rheumatol 21(3 Suppl 29):S42–S46PubMed
26.
go back to reference Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198CrossRef Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198CrossRef
27.
go back to reference Williams JM (1991) Memory assessment scales. Odessa, Psychological Assessment Resources 199 (1) Williams JM (1991) Memory assessment scales. Odessa, Psychological Assessment Resources 199 (1)
28.
go back to reference Polich J (1998) P300 clinical utility and control of variability. J Clin Neurophysiol 15(1):14–33PubMedCrossRef Polich J (1998) P300 clinical utility and control of variability. J Clin Neurophysiol 15(1):14–33PubMedCrossRef
29.
go back to reference Chapman RM, Bragdon HR (1964) Evoked responses to numerical and non-numerical visual stimuli while problem solving. Nature 203(4950):1155PubMedCrossRef Chapman RM, Bragdon HR (1964) Evoked responses to numerical and non-numerical visual stimuli while problem solving. Nature 203(4950):1155PubMedCrossRef
30.
go back to reference van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Muller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Ellen Csuka M, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE (2013) 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Ann Rheum Dis 72(11):1747–1755. https://doi.org/10.1136/annrheumdis-2013-204424 PubMedCrossRef van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Muller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Ellen Csuka M, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE (2013) 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Ann Rheum Dis 72(11):1747–1755. https://​doi.​org/​10.​1136/​annrheumdis-2013-204424 PubMedCrossRef
34.
go back to reference Giuliodori G, Fraticelli P, Bartolini M, Cagnetti C, Baruffaldi R, Rocchi MBL, Provinciali L, Gabrielli A, Silvestrini M (2009) Cognitive and cerebral hemodynamic impairment in scleroderma patients. Eur J Neurol 16(12):1285–1290PubMedCrossRef Giuliodori G, Fraticelli P, Bartolini M, Cagnetti C, Baruffaldi R, Rocchi MBL, Provinciali L, Gabrielli A, Silvestrini M (2009) Cognitive and cerebral hemodynamic impairment in scleroderma patients. Eur J Neurol 16(12):1285–1290PubMedCrossRef
35.
go back to reference Yilmaz N, Mollahasanoglu A, Gurvit H, Can M, Tuncer N, Inanc N, Yavuz S (2012) Dysexecutive syndrome: a specific pattern of cognitive impairment in systemic sclerosis. Cogn Behav Neurol 25(2):57–62PubMedCrossRef Yilmaz N, Mollahasanoglu A, Gurvit H, Can M, Tuncer N, Inanc N, Yavuz S (2012) Dysexecutive syndrome: a specific pattern of cognitive impairment in systemic sclerosis. Cogn Behav Neurol 25(2):57–62PubMedCrossRef
36.
go back to reference Silvestrini M, Vernieri F, Pasqualetti P, Matteis M, Passarelli F, Troisi E, Caltagirone C (2000) Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis. Jama 283(16):2122–2127PubMedCrossRef Silvestrini M, Vernieri F, Pasqualetti P, Matteis M, Passarelli F, Troisi E, Caltagirone C (2000) Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis. Jama 283(16):2122–2127PubMedCrossRef
37.
go back to reference Heron E, Fornes P, Rance A, Emmerich J, Bayle O, Fiessinger JN (1998) Brain involvement in scleroderma: two autopsy cases. Stroke 29(3):719–721PubMedCrossRef Heron E, Fornes P, Rance A, Emmerich J, Bayle O, Fiessinger JN (1998) Brain involvement in scleroderma: two autopsy cases. Stroke 29(3):719–721PubMedCrossRef
41.
go back to reference Carvalho D, Savage CO, Black CM, Pearson JD (1996) IgG antiendothelial cell autoantibodies from scleroderma patients induce leukocyte adhesion to human vascular endothelial cells in vitro. Induction of adhesion molecule expression and involvement of endothelium-derived cytokines. J Clin Invest 97(1):111–119. https://doi.org/10.1172/jci118377 PubMedPubMedCentralCrossRef Carvalho D, Savage CO, Black CM, Pearson JD (1996) IgG antiendothelial cell autoantibodies from scleroderma patients induce leukocyte adhesion to human vascular endothelial cells in vitro. Induction of adhesion molecule expression and involvement of endothelium-derived cytokines. J Clin Invest 97(1):111–119. https://​doi.​org/​10.​1172/​jci118377 PubMedPubMedCentralCrossRef
44.
go back to reference Jarius S, Jacobi C, de Seze J, Zephir H, Paul F, Franciotta D, Rommer P, Mader S, Kleiter I, Reindl M, Akman-Demir G, Seifert-Held T, Kristoferitsch W, Melms A, Wandinger K-P, Wildemann B (2011) Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders. Mult Scler J 17(9):1067–1073. https://doi.org/10.1177/1352458511403958 CrossRef Jarius S, Jacobi C, de Seze J, Zephir H, Paul F, Franciotta D, Rommer P, Mader S, Kleiter I, Reindl M, Akman-Demir G, Seifert-Held T, Kristoferitsch W, Melms A, Wandinger K-P, Wildemann B (2011) Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders. Mult Scler J 17(9):1067–1073. https://​doi.​org/​10.​1177/​1352458511403958​ CrossRef
Metadata
Title
Evaluation of cognitive function in systemic sclerosis patients: a pilot study
Authors
Eman M. Khedr
Noha Abo El Fetoh
Rania M. Gamal
Mona H. Elzohri
Nashwa Mostafa A. Azoz
Daniel E. Furst
Publication date
01-05-2020
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 5/2020
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-019-04884-9

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