Skip to main content
Top
Published in: Rheumatology International 8/2018

01-08-2018 | Observational Research

Correlation of neurocognitive function and brain lesion load on magnetic resonance imaging in systemic lupus erythematosus

Authors: Paola C. Roldan, Rex E. Jung, Wilmer L. Sibbitt, Clifford R. Qualls, Ranee A. Flores, Carlos A. Roldan

Published in: Rheumatology International | Issue 8/2018

Login to get access

Abstract

Neurocognitive dysfunction and brain injury on magnetic resonance imaging (MRI) are common in patients with systemic lupus erythematosus (SLE) and are associated with increased morbidity and mortality. However, brain MRI is expensive, is restricted by payers, and requires high expertise. Neurocognitive assessment is an easily available, safe, and inexpensive clinical tool that may select patients needing brain MRI. In this cross-sectional and controlled study, 76 SLE patients (69 women, age 37 ± 12 years) and 26 age and gender-matched healthy subjects (22 women, age 34 ± 11 years) underwent assessment of attention, memory, processing speed, executive function, motor function, and global neurocognitive function. All subjects underwent brain MRI with T1-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging. Hemispheric and whole brain lesion load in cm3 were determined using semi-automated methods. Neurocognitive z-scores in all clinical domains were significantly lower and whole brain and right and left hemispheres brain lesion load were significantly greater in patients than in controls (all p ≤ 0.02). There was significant correlation between neurocognitive z-scores in all domains and whole brain lesion load: processing speed (r = − 0.46; p < 0.0001), attention (r = − 0.42; p < 0.001), memory (r = − 0.40; p = 0.0004), executive function (r = − 0.25; p = 0.03), motor function (r = − 0.25; p = 0.05), and global neurocognitive function (r = − 0.38; p = 0.006). Similar correlations were found for brain hemisphere lesion loads (all p ≤ 0.05). These correlations were strengthened when adjusted for glucocorticoid therapy and SLE disease activity index. Finally, global neurocognitive z-score and erythrosedimentation rate were the only independent predictors of whole brain lesion load (both p ≤ 0.007). Neurocognitive measures and brain lesion load are worse in SLE patients than in controls. In SLE patients, neurocognitive z-scores correlate negatively with and independently predict brain lesion load. Therefore, neurocognitive testing may be an effective clinical tool to select patients needing brain MRI.
Literature
1.
go back to reference Carbotte RM, Denburg SD, Denburg JA (1986) Prevalence of cognitive impairment in systemic lupus erythematosus. J Nerv Ment Dis 174:357–364CrossRef Carbotte RM, Denburg SD, Denburg JA (1986) Prevalence of cognitive impairment in systemic lupus erythematosus. J Nerv Ment Dis 174:357–364CrossRef
2.
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 184:33–39CrossRef 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 184:33–39CrossRef
3.
go back to reference Sabet A, Sibbitt WL Jr, Stidley CA, Danska J, Brooks WM (1998) Neurometabolite markers of cerebral injury in the antiphospholipid antibody syndrome of systemic lupus erythematosus. Stroke 29:2254–2260CrossRef Sabet A, Sibbitt WL Jr, Stidley CA, Danska J, Brooks WM (1998) Neurometabolite markers of cerebral injury in the antiphospholipid antibody syndrome of systemic lupus erythematosus. Stroke 29:2254–2260CrossRef
4.
go back to reference Sibbitt WL Jr, Brooks WM, Kornfeld M, Hart BL, Bankhurst AD, Roldan CA (2010) Magnetic resonance imaging and brain histopathology in neuropsychiatric systemic lupus erythematosus. Semin Arthritis Rheum 40:32–52CrossRef Sibbitt WL Jr, Brooks WM, Kornfeld M, Hart BL, Bankhurst AD, Roldan CA (2010) Magnetic resonance imaging and brain histopathology in neuropsychiatric systemic lupus erythematosus. Semin Arthritis Rheum 40:32–52CrossRef
5.
go back to reference Navarrete MG, Brey RL (2000) Neuropsychiatric systemic lupus erythematosus. Curr Treat Options Neurol 2:473–485CrossRef Navarrete MG, Brey RL (2000) Neuropsychiatric systemic lupus erythematosus. Curr Treat Options Neurol 2:473–485CrossRef
6.
go back to reference Luyendijk J, Steens SC, Ouwendijk WJ, Steup-Beekman GM, Bollen EL, van der Grond J, Huizinga TW, Emmer BJ, van Buchem MA (2011) Neuropsychiatric systemic lupus erythematosus: lessons learned from magnetic resonance imaging. Arthritis Rheum 63:722–732CrossRef Luyendijk J, Steens SC, Ouwendijk WJ, Steup-Beekman GM, Bollen EL, van der Grond J, Huizinga TW, Emmer BJ, van Buchem MA (2011) Neuropsychiatric systemic lupus erythematosus: lessons learned from magnetic resonance imaging. Arthritis Rheum 63:722–732CrossRef
7.
go back to reference Jung RE, Chavez RS, Flores RA, Qualls C, Sibbitt WL Jr, Roldan CA (2012) White matter correlates of neuropsychological dysfunction in systemic lupus erythematosus. PLoS One 7:e28373CrossRef Jung RE, Chavez RS, Flores RA, Qualls C, Sibbitt WL Jr, Roldan CA (2012) White matter correlates of neuropsychological dysfunction in systemic lupus erythematosus. PLoS One 7:e28373CrossRef
8.
go back to reference Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640CrossRef Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640CrossRef
9.
go back to reference Scully M, Anderson B, Lane T, Gasparovic C, Magnotta V, Sibbitt W, Roldan C, Kikinis R, Bockholt HJ (2010) An automated method for segmenting white matter lesions through multi-level morphometric feature classification with application to lupus. Front Hum Neurosci 19:4:27 Scully M, Anderson B, Lane T, Gasparovic C, Magnotta V, Sibbitt W, Roldan C, Kikinis R, Bockholt HJ (2010) An automated method for segmenting white matter lesions through multi-level morphometric feature classification with application to lupus. Front Hum Neurosci 19:4:27
10.
go back to reference Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 40:1725CrossRef Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 40:1725CrossRef
11.
go back to reference Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C, Hanly JG, Isenberg DA, Kalunian K, Nived O, Petri M, Sanchez-Guerrero J, Snaith M, Sturfelt G (1997) The reliability of the systemic lupus international collaborating clinics/American College of rheumatology damage index in patients with systemic lupus erythematosus. Arthritis Rheum 40:809–813CrossRef Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C, Hanly JG, Isenberg DA, Kalunian K, Nived O, Petri M, Sanchez-Guerrero J, Snaith M, Sturfelt G (1997) The reliability of the systemic lupus international collaborating clinics/American College of rheumatology damage index in patients with systemic lupus erythematosus. Arthritis Rheum 40:809–813CrossRef
12.
go back to reference Kozora E, Ellison MC, West S (2004) Reliability and validity of the proposed American College of Rheumatology neuropsychological battery for systemic lupus erythematosus. Arthritis Rheum 51:810–818CrossRef Kozora E, Ellison MC, West S (2004) Reliability and validity of the proposed American College of Rheumatology neuropsychological battery for systemic lupus erythematosus. Arthritis Rheum 51:810–818CrossRef
13.
go back to reference Brooks WM, Jung RE, Ford CC, Greinel EJ, Sibbitt WL Jr (1999) Jr. Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus. J Rheumatol 26:81–85PubMed Brooks WM, Jung RE, Ford CC, Greinel EJ, Sibbitt WL Jr (1999) Jr. Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus. J Rheumatol 26:81–85PubMed
14.
go back to reference Roldan CA, Sibbitt WL Jr, Qualls CR, Jung RE, Greene ER, Gasparovic CM, Hayek RA, Charlton GA, Crookston K (2013) Libman-sacks endocarditis and embolic cerebrovascular disease. JACC Cardiovasc Imaging 6:973–83CrossRef Roldan CA, Sibbitt WL Jr, Qualls CR, Jung RE, Greene ER, Gasparovic CM, Hayek RA, Charlton GA, Crookston K (2013) Libman-sacks endocarditis and embolic cerebrovascular disease. JACC Cardiovasc Imaging 6:973–83CrossRef
15.
go back to reference Aisen AM, Gabrielsen TO, McCune WJ (1985) MR imaging of systemic lupus erythematosus involving the brain. Am J Roentgenol 144:1027–1031CrossRef Aisen AM, Gabrielsen TO, McCune WJ (1985) MR imaging of systemic lupus erythematosus involving the brain. Am J Roentgenol 144:1027–1031CrossRef
16.
go back to reference McCune WJ, MacGuire A, Aisen A, Gebarski S (1988) Identification of brain lesions in neuropsychiatric systemic lupus erythematosus by magnetic resonance scanning. Arthritis Rheum 31:159–66CrossRef McCune WJ, MacGuire A, Aisen A, Gebarski S (1988) Identification of brain lesions in neuropsychiatric systemic lupus erythematosus by magnetic resonance scanning. Arthritis Rheum 31:159–66CrossRef
17.
go back to reference Brooks WM, Sabet A, Sibbitt WL Jr, Barker PB, van Zijl PC, Duyn JH, Moonen CT (1997) Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus. J Rheum 24:2323–2329PubMed Brooks WM, Sabet A, Sibbitt WL Jr, Barker PB, van Zijl PC, Duyn JH, Moonen CT (1997) Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus. J Rheum 24:2323–2329PubMed
18.
go back to reference Sibbitt WL Jr, Sibbitt RR, Brooks WM (1999) Neuroimaging in neuropsychiatric SLE. Arthritis Rheum 42:2026–2038CrossRef Sibbitt WL Jr, Sibbitt RR, Brooks WM (1999) Neuroimaging in neuropsychiatric SLE. Arthritis Rheum 42:2026–2038CrossRef
19.
go back to reference Jarek M, West SG, Baker MR et al (1994) Magnetic resonance imaging in systemic lupus erythematosus patients without a history of neuropsychiatric lupus erythematosus. Arthritis Rheum 37:1609–1613CrossRef Jarek M, West SG, Baker MR et al (1994) Magnetic resonance imaging in systemic lupus erythematosus patients without a history of neuropsychiatric lupus erythematosus. Arthritis Rheum 37:1609–1613CrossRef
20.
go back to reference Sibbitt WL Jr, Sibbitt RR, Griffey RH, Eckel C, Bankhurst AD (1989) Magnetic resonance and CT imaging in the evaluation of acute neuropsychiatric disease in systemic lupus erythematosus. Ann Rheum Dis 48:1014–1022CrossRef Sibbitt WL Jr, Sibbitt RR, Griffey RH, Eckel C, Bankhurst AD (1989) Magnetic resonance and CT imaging in the evaluation of acute neuropsychiatric disease in systemic lupus erythematosus. Ann Rheum Dis 48:1014–1022CrossRef
21.
go back to reference Kozora E, West SG, Kotzin BL, Julian l, Porter S, Bigler E (1998) Magnetic resonance imaging abnormalities and cognitive defects in systemic lupus erythematosus patients without overt central nervous system disease. Arthritis Rheum 41:41–47CrossRef Kozora E, West SG, Kotzin BL, Julian l, Porter S, Bigler E (1998) Magnetic resonance imaging abnormalities and cognitive defects in systemic lupus erythematosus patients without overt central nervous system disease. Arthritis Rheum 41:41–47CrossRef
22.
go back to reference Turken A, Whitfield-Gabrieli S, Bammer R, Baldo JV, Dronkers NF, Gabrieli JD (2008) Cognitive processing speed and the structure of white matter pathways: convergent evidence from normal variation and lesion studies. Neuroimage 42:1032–1044CrossRef Turken A, Whitfield-Gabrieli S, Bammer R, Baldo JV, Dronkers NF, Gabrieli JD (2008) Cognitive processing speed and the structure of white matter pathways: convergent evidence from normal variation and lesion studies. Neuroimage 42:1032–1044CrossRef
23.
go back to reference Johnson R, Richardson EP (1968) The neurological manifestations of systemic lupus erythematosus. A clinical-pathological study of 24 cases and review of the literature. Medicine 47:337–369CrossRef Johnson R, Richardson EP (1968) The neurological manifestations of systemic lupus erythematosus. A clinical-pathological study of 24 cases and review of the literature. Medicine 47:337–369CrossRef
24.
go back to reference Ellis SG, Verity MA (1979) Central nervous systemic involvement in systemic lupus erythematosus: a review of neuropathological findings in 57 cases, 1955–1977. Semin Arthritis Rheum 8:212–221CrossRef Ellis SG, Verity MA (1979) Central nervous systemic involvement in systemic lupus erythematosus: a review of neuropathological findings in 57 cases, 1955–1977. Semin Arthritis Rheum 8:212–221CrossRef
25.
go back to reference Hanly JG, Walsh N, Sangalang V (1992) Brain pathology in systemic lupus erythematosus. J Rheumatol 19:732–741PubMed Hanly JG, Walsh N, Sangalang V (1992) Brain pathology in systemic lupus erythematosus. J Rheumatol 19:732–741PubMed
26.
go back to reference Belmont HM, Abramson SB, Lie JT (1996) Pathology and pathogenesis of vascular injury in systemic lupus erythematosus: interactions of inflammatory cells and activated endothelium. Arthritis Rheum 39:9–22CrossRef Belmont HM, Abramson SB, Lie JT (1996) Pathology and pathogenesis of vascular injury in systemic lupus erythematosus: interactions of inflammatory cells and activated endothelium. Arthritis Rheum 39:9–22CrossRef
27.
go back to reference Sarbu N, Alobeidi F, Toledano P, Espinosa G, Giles I, Rahman A, Yousry T, Capurro S, Jäger R, Cervera R, Bargalló N (2015) Brain abnormalities in newly diagnosed neuropsychiatric lupus: systematic MRI approach and correlation with clinical and laboratory data in a large multicenter cohort. Autoimmun Rev 14:153–159CrossRef Sarbu N, Alobeidi F, Toledano P, Espinosa G, Giles I, Rahman A, Yousry T, Capurro S, Jäger R, Cervera R, Bargalló N (2015) Brain abnormalities in newly diagnosed neuropsychiatric lupus: systematic MRI approach and correlation with clinical and laboratory data in a large multicenter cohort. Autoimmun Rev 14:153–159CrossRef
28.
go back to reference Cohen D, Rijnink EC, Nabuurs RJ, Steup-Beekman GM, Versluis MJ, Emmer BJ, Zandbergen M, van Buchem MA, Allaart CF, Wolterbeek R, Bruijn JA, van Duinen SG, Huizinga TW, Bajema IM (2017) Brain histopathology in patients with systemic lupus erythematosus: identification of lesions associated with clinical neuropsychiatric lupus syndromes and the role of complement. Rheumatology (Oxford) 56:77–86CrossRef Cohen D, Rijnink EC, Nabuurs RJ, Steup-Beekman GM, Versluis MJ, Emmer BJ, Zandbergen M, van Buchem MA, Allaart CF, Wolterbeek R, Bruijn JA, van Duinen SG, Huizinga TW, Bajema IM (2017) Brain histopathology in patients with systemic lupus erythematosus: identification of lesions associated with clinical neuropsychiatric lupus syndromes and the role of complement. Rheumatology (Oxford) 56:77–86CrossRef
29.
go back to reference Jeong HW1, Her M, Bae JS, Kim SK, Lee SW, Kim HK, Kim D, Park N, Chung WT, Lee SY, Choe JY, Kim IJ (2015) Brain MRI in neuropsychiatric lupus: associations with the 1999 ACR case definitions. Rheumatol Int 35:861–869CrossRef Jeong HW1, Her M, Bae JS, Kim SK, Lee SW, Kim HK, Kim D, Park N, Chung WT, Lee SY, Choe JY, Kim IJ (2015) Brain MRI in neuropsychiatric lupus: associations with the 1999 ACR case definitions. Rheumatol Int 35:861–869CrossRef
30.
go back to reference Hanly JG, Urowitz MB, Su L, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, Isenberg D, Alarcón GS, Merrill JT, Clarke A, Bernatsky S, Dooley MA, Fortin PR, Gladman D, Steinsson K, Petri M, Bruce IN, Manzi S, Khamashta M, Zoma A, Font J, Van Vollenhoven R, Aranow C, Ginzler E, Nived O, Sturfelt G, Ramsey-Goldman R, Kalunian K, Douglas J, Qiufen Qi K, Thompson K, Farewell V; Systemic Lupus International Collaborating Clinics (2008) Short-term outcome of neuropsychiatric events in systemic lupus erythematosus upon enrollment into an international inception cohort study. Arthritis Rheum 59:721–729CrossRef Hanly JG, Urowitz MB, Su L, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, Isenberg D, Alarcón GS, Merrill JT, Clarke A, Bernatsky S, Dooley MA, Fortin PR, Gladman D, Steinsson K, Petri M, Bruce IN, Manzi S, Khamashta M, Zoma A, Font J, Van Vollenhoven R, Aranow C, Ginzler E, Nived O, Sturfelt G, Ramsey-Goldman R, Kalunian K, Douglas J, Qiufen Qi K, Thompson K, Farewell V; Systemic Lupus International Collaborating Clinics (2008) Short-term outcome of neuropsychiatric events in systemic lupus erythematosus upon enrollment into an international inception cohort study. Arthritis Rheum 59:721–729CrossRef
31.
go back to reference Roldan CA, Gelgand EA, Qualls CR, Sibbitt WL Jr (2006) Valvular heart disease is associated with non-focal neuropsychiatric systemic lupus erythematosus. J Clin Rheumatol 12:3–10CrossRef Roldan CA, Gelgand EA, Qualls CR, Sibbitt WL Jr (2006) Valvular heart disease is associated with non-focal neuropsychiatric systemic lupus erythematosus. J Clin Rheumatol 12:3–10CrossRef
32.
go back to reference DeGiorgio LA, Konstantinov KN, Lee SC et al (2001) A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 7:1189–1193CrossRef DeGiorgio LA, Konstantinov KN, Lee SC et al (2001) A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 7:1189–1193CrossRef
33.
go back to reference Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330:613–22CrossRef Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330:613–22CrossRef
Metadata
Title
Correlation of neurocognitive function and brain lesion load on magnetic resonance imaging in systemic lupus erythematosus
Authors
Paola C. Roldan
Rex E. Jung
Wilmer L. Sibbitt
Clifford R. Qualls
Ranee A. Flores
Carlos A. Roldan
Publication date
01-08-2018
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 8/2018
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-018-4080-7

Other articles of this Issue 8/2018

Rheumatology International 8/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.