Our aim was to assess the contribution of depression to cognitive impairment in patients with systemic lupus erythematosus (SLE).
Methods
Clinical features, education, age, and Hospital Anxiety and Depression Scale (HADS) were evaluated in 82 patients with SLE and 22 healthy controls, all Chilean women. The Cambridge Neuropsychological Test Automated Battery (CANTAB eclipseTM) assessing attention, spatial memory, and learning and executive function domains was applied. Cognitive deficit definition: a cut-off for definite impairment was defined as a score below -2 standard deviations in at least one outcome measure in two or more domains. ANCOVA with stepwise selection evaluated influences of health status (SLE or control), age, education, and HADS depression and anxiety scores on cognitive outcomes. To avoid overfitting, a shrinkage method was performed. Also, adjusted p-values for multiple comparisons were obtained.
Results
Cognitive deficit affected 16 (20%) patients, and no controls (p = 0.039). Median HADS depression score in SLE patients was 6 (range 0–19) and in controls was 0 (0–19), p < 0.001). ANCOVA and shrinkage models showed that worse cognitive performance in sustained attention and spatial working memory tests was explained by the presence of SLE but not depression, whereas depression only affected a measure of executive function (I/ED Stages completed).
Conclusion
Depression has a limited role in cognitive impairment in SLE. Impairments in sustained attention and spatial working memory are distinctly influenced by yet-unknown disease-intrinsic factors.
AustinMPMitchellPGoodwinGM. Cognitive deficits in depression: possible implications for functional neuropathology. Br J Psychiatry2001; 178: 200–206.
2.
HammarAArdalG. Cognitive functioning in major depression – a summary. Front Hum Neurosci2009; 3: 26–26.
3.
ChodoshJKadoDMSeemanTEKarlamanglaAS. Depressive symptoms as a predictor of cognitive decline: MacArthur Studies of Successful Aging. Am J Geriatr Psychiatry2007; 15: 406–415.
4.
BauneBTMillerRMcAfooseJJohnsonMQuirkFMitchellD. The role of cognitive impairment in general functioning in major depression. Psychiatry Res2010; 176: 183–189.
5.
ACR. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum1999; 42: 599–608.
6.
BertsiasGKBoumpasDT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol2010; 6: 358–367.
7.
HanlyJG. Neuropsychiatric lupus. Rheum Dis Clin North Am2005; 31: 273–298, vi.
8.
PetriMNaqibuddinMCarsonKA. Depression and cognitive impairment in newly diagnosed systemic lupus erythematosus. J Rheumatol2010; 37: 2032–2038.
9.
JarpaEBabulMCalderonJ. Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity. Lupus2011; 20: 58–66.
10.
NeryFGBorbaEFHatchJPSoaresJCBonfaENetoFL. Major depressive disorder and disease activity in systemic lupus erythematosus. Compr Psychiatry2007; 48: 14–19.
11.
KozoraEErkanDWestSG. Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE). Lupus2013; 22: 73–80.
12.
DenburgSDDenburgJA. Cognitive dysfunction and antiphospholipid antibodies in systemic lupus erythematosus. Lupus2003; 12: 883–890.
13.
PanopalisPJulianLYazdanyJ. Impact of memory impairment on employment status in persons with systemic lupus erythematosus. Arthritis Rheum2007; 57: 1453–1460.
14.
AppenzellerSCendesFCostallatLT. Cognitive impairment and employment status in systemic lupus erythematosus: A prospective longitudinal study. Arthritis Rheum2009; 61: 680–687.
15.
LoukkolaJLaineMAinialaH. Cognitive impairment in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus: A population-based neuropsychological study. J Clin Exp Neuropsychol2003; 25: 145–151.
16.
ShucardJLParrishJShucardDWMcCabeDCBenedictRHAmbrusJJr. Working memory and processing speed deficits in systemic lupus erythematosus as measured by the paced auditory serial addition test. J Int Neuropsychol Soc2004; 10: 35–45.
17.
BenedictRHShucardJLZivadinovRShucardDW. Neuropsychological impairment in systemic lupus erythematosus: A comparison with multiple sclerosis. Neuropsychol Rev2008; 18: 149–166.
18.
MonasteroRBettiniPDel ZottoE. Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations. J Neurol Sci2001; 184: 33–39.
19.
KozoraEArciniegasDBZhangLWestS. Neuropsychological patterns in systemic lupus erythematosus patients with depression. Arthritis Res Ther2007; 9: R48–R48.
20.
TomiettoPAnneseVD'AgostiniS. General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Rheum2007; 57: 1461–1472.
21.
ErkanDKozoraELockshinMD. Cognitive dysfunction and white matter abnormalities in antiphospholipid syndrome. Pathophysiology2011; 18: 93–102.
22.
HanlyJGFiskJD. Diagnosis of cognitive impairment in adult and pediatric SLE. Nat Rev Rheumatol2011; 7: 564–565.
23.
WilliamsTSAranowCRossGS. Neurocognitive impairment in childhood-onset systemic lupus erythematosus: Measurement issues in diagnosis. Arthritis Care Res (Hoboken)2011; 63: 1178–1187.
24.
CognitionS-cMikdashiJAEsdaileJM. Ad Hoc Committee on Lupus Response Criteria. Proposed response criteria for neurocognitive impairment in systemic lupus erythematosus clinical trials. Lupus2007; 16: 418–425.
25.
HanlyJGOmisadeASuLFarewellVFiskJD. Assessment of cognitive function in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis by computerized neuropsychological tests. Arthritis Rheum2010; 62: 1478–1486.
26.
ReevesDBleibergJSpectorJ. Validation of the ANAM Battery in Multi-center head injury studies. Arch Clin Neuropsychol1993; 8: 356–356.
27.
BreyRLHollidaySLSakladAR. Neuropsychiatric syndromes in lupus: Prevalence using standardized definitions. Neurology2002; 58: 1214–1220.
28.
RobbinsTWJamesMOwenAMSahakianBJMcInnesLRabbittP. Cambridge Neuropsychological Test Automated Battery (CANTAB): A factor analytic study of a large sample of normal elderly volunteers. Dementia1994; 5: 266–281.
29.
WildKHowiesonDWebbeFSeelyeAKayeJ. Status of computerized cognitive testing in aging: A systematic review. Alzheimers Dement2008; 4: 428–437.
30.
OwenAMRobertsACPolkeyCESahakianBJRobbinsTW. Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia1991; 29: 993–1006.
31.
BarnettJHSahakianBJWernersU. Visuospatial learning and executive function are independently impaired in first-episode psychosis. Psychol Med2005; 35: 1031–1041.
32.
DisnerSGBeeversCGHaighEABeckAT. Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci2011; 12: 467–477.
33.
KozoraEBrownMSFilleyCM. Memory impairment associated with neurometabolic abnormalities of the hippocampus in patients with non-neuropsychiatric systemic lupus erythematosus. Lupus2011; 20: 598–606.
34.
LaptevaLNowakMYarboroCH. Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum2006; 54: 2505–2514.
35.
MatusSBurgosPVBravo-ZehnderM. Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis. J Exp Med2007; 204: 3221–3234.
36.
DiamondBHuertaPTMina-OsorioPKowalCVolpeBT. Losing your nerves? Maybe it's the antibodies. Nat Rev Immunol2009; 9: 449–456.
37.
HochbergMC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725–1725.
38.
InouyeSKvan DyckCHAlessiCABalkinSSiegalAPHorwitzRI. Clarifying confusion: The confusion assessment method. A new method for detection of delirium. Ann Intern Med1990; 113: 941–948.
39.
MioshiEDawsonKMitchellJArnoldRHodgesJR. The Addenbrooke's Cognitive Examination Revised (ACE-R): A brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry2006; 21: 1078–1085.
GladmanDDGoldsmithCHUrowitzMB. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison. J Rheumatol2000; 27: 373–376.
42.
MiyakisSLockshinMDAtsumiT. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost2006; 4: 295–306.
43.
ZigmondASSnaithRP. The hospital anxiety and depression scale. Acta Psychiatr Scand1983; 67: 361–370.
44.
SheehanDVLecrubierYSheehanKH. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry1998; 59(Suppl 20): 22–33; quiz 4-57.
45.
Diagnostic and Statistical Manual of Mental Disorders-IV. 4th ed. Washington: American Psychiatric Association, 2004.
46.
ParkSBCoullJTMcShaneRH. Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology1994; 33: 575–588.
47.
SahakianBJCoullJT. Tetrahydroaminoacridine (THA) in Alzheimer's disease: An assessment of attentional and mnemonic function using CANTAB. Acta Neurol Scand Suppl1993; 149: 29–35.
48.
OwenAMSahakianBJSempleJPolkeyCERobbinsTW. Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia1995; 33: 1–24.
49.
DiasRRobbinsTWRobertsAC. Dissociation in prefrontal cortex of affective and attentional shifts. Nature1996; 380: 69–72.
50.
ShalliceT. Specific impairments of planning. Philos Trans Roy Soc Lond Series B, Biol Sci1982; 298: 199–209.
51.
ChaseHWClarkLSahakianBJBullmoreETRobbinsTW. Dissociable roles of prefrontal subregions in self-ordered working memory performance. Neuropsychologia2008; 46: 2650–2661.
52.
YamashitaCHYamashitaKKamimuraR. A stepwise AIC method for variable selection in linear regression. Comm Stat Theory Methods2007; 36: 2395–2403.
53.
BabyakMA. What you see may not be what you get: A brief, nontechnical introduction to overfitting in regression-type models. Psychosom Med2004; 66: 411–421.
54.
TibishiraniR. Regression shrinkage and selection via the Lasso. J Royal Stat Soc Series B (Methodological)1996; 58: 267–288.
55.
BlakesleyREMazumdarSDewMA. Comparisons of methods for multiple hypothesis testing in neuropsychological research. Neuropsychology2009; 23: 255–264.
56.
KozoraEArciniegasDBFilleyCM. Cognitive and neurologic status in patients with systemic lupus erythematosus without major neuropsychiatric syndromes. Arthritis Rheum2008; 59: 1639–1646.
57.
MichopoulosIZervasIMPantelisC. Neuropsychological and hypothalamic-pituitary-axis function in female patients with melancholic and non-melancholic depression. Eur Arch Psychiatry Clin Neurosci2008; 258: 217–225.
58.
de RoverMPirontiVAMcCabeJA. Hippocampal dysfunction in patients with mild cognitive impairment: A functional neuroimaging study of a visuospatial paired associates learning task. Neuropsychologia2011; 49: 2060–2070.
59.
GlanzBISchurPHLewRAKhoshbinS. Lateralized cognitive dysfunction in patients with systemic lupus erythematosus. Lupus2005; 14: 896–902.
60.
PetriMNaqibuddinMCarsonKA. Cognitive function in a systemic lupus erythematosus inception cohort. J Rheumatol2008; 35: 1776–1781.
61.
KaneRLRoebuck-SpencerTShortPKabatMWilkenJ. Identifying and monitoring cognitive deficits in clinical populations using Automated Neuropsychological Assessment Metrics (ANAM) tests. Arch Clin Neuropsychol2007; 22(Suppl 1): S115–S126.
