Abstract

Objective. To evaluate potential changes in cognitive functions over a 5‐yr period in patients with systemic lupus erythematosus (SLE).

Methods. Twenty‐eight patients with SLE were examined at baseline and after a mean follow‐up of 60.7±5.0 months using standardized neuropsychological tests. Group changes in performance over time were measured and the effects of baseline values for subsequent changes in individual variables after 5 yr were evaluated.

Results. When all SLE patients were considered as a group, seven out of nine (78%) neuropsychological variables remained unchanged and two (22%) improved significantly during the observation period, possibly due to methodological bias. Analysis of the importance of the level of initial cognitive performance for subsequent changes during the observation period, demonstrated that cognitive changes were not significantly influenced by baseline levels, except for a trend in three of nine variables. Neither demographic nor disease‐associated quantitative factors were associated with cognitive changes over time.

Conclusion. Cognitive dysfunction seems to be a relatively stable feature of central nervous system involvement in SLE. A decrease in performance over time was not demonstrated consistently in the majority of domains.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune, multiorganic disease with a broad spectrum of clinical manifestations. SLE with involvement of the central nervous system (CNS), which is often called neuropsychiatric SLE (NPSLE), is one of the most important manifestations of SLE [1]. The condition may be both neurological and psychological [2, 3], and the reported prevalence of CNS involvement varies in different studies [48]. This probably reflects differences in patient selection, different criteria for NPSLE, differences in the neuropsychological tests used and the lack of standard diagnostic instruments for CNS manifestations. Cognitive dysfunction appears to be more common than previously thought, but its clinical significance and prognostic implications remain unclear.

The pathogenesis of CNS dysfunction in SLE is not well understood. The observation of both diffuse and focal CNS involvement in SLE has led to the hypothesis that there are several pathogenic mechanisms in NPSLE, such as microvascular damage, small‐vessel vasculopathy and autoantibody‐mediated neuronal cell injury [912]. It has been proposed that antineuronal and antiphospholipid antibodies are related to NPSLE features, such as cognitive dysfunction, but their pathogenic role in the induction of cognitive deficits remains uncertain. Some studies [1215] have suggested a relationship between anticardiolipin (aCL) antibody, lupus anticoagulant and cognitive function, while one study found no such association [16]. We have not previously seen any association between lupus anticoagulant or aCL antibody and cognitive abnormalities [17], although we have demonstrated that patients with SLE have significant cognitive abnormalities compared with patients with a chronic, non‐immunological illness [18]. Furthermore, there were no associations between cognitive dysfunction and depression, indicating that cognitive dysfunction in SLE reflects CNS involvement and is not related to coexisting depressive disturbances [18]. Two recently published longitudinal studies demonstrated an association between persistently elevated aCL titres and cognitive dysfunction, suggesting that aCL may serve as an immunological marker [19, 20]. Most studies have found no associations between cognitive dysfunction and clinical or laboratory markers of disease activity, severity or corticosteroid medication [16, 21, 22].

Most studies on cognitive dysfunction in SLE have been cross‐sectional in design. However, it is important to know whether these abnormalities are static or progressive or if they resolve over time. Furthermore, it is important to elucidate the long‐term implications of cognitive dysfunction in SLE patients and to determine whether such patients require aggressive medication, including prophylactic anticoagulation, to prevent cerebral infarction [17]. Few longitudinal studies have been reported [2325], only one being a long‐term (5 yr) follow‐up study [26]. We therefore performed a longitudinal study, also focusing on factors of possible importance in the development of cognitive dysfunction in SLE patients over time.

Patients and methods

Forty‐three consecutive SLE patients seen as out‐patients at the Departments of Rheumatology and Internal Medicine of the University Hospital of Tromsø during 1991 were asked to participate in the study. One patient was excluded due to dementia known to be caused by meningoencephalitis. Six patients declined the invitation to participate, rejected examination or never returned their questionnaires. Thus, 36 patients with SLE (33 females and three males) underwent neuropsychological assessment. The patients gave informed consent to be included in the study, which was approved by the Regional Research Ethics Committee. All patients fulfilled the 1982 revised criteria of the American College of Rheumatology (ACR) for SLE [27]. Five years later, in 1996, the same 36 patients were invited to participate in this follow‐up study. Six patients (17%) were now dead. One patient had moved to another part of the country and one patient refused to participate. Twenty‐eight SLE patients were thus available for follow‐up examination, the mean follow‐up time being 60.7±5.0 months (range 50–70 months).

Demographic and clinical data at inclusion in 1991

Twenty‐six females (93%) and two males (7%) were included. The mean age was 41.0±12.2 yr (range 20–67 yr), mean education level 10.6±3.4 yr (range 5–19 yr), and mean disease duration 13.8±6.4 yr (range 6.0–31.0 yr). Disease duration was defined as the interval between the time of assessment and the onset of symptoms or signs attributable to SLE. Nineteen patients (68%) were on medication for SLE with a single drug or a combinations of drugs. Thirteen patients (46%) used corticosteroids, 12 (43%) antimalarials and nine (32%) azathioprine, while nine patients (32%) were not on medication for SLE. None used antidepressive drugs. The most frequent disease complication was glomerulonephritis, in five patients (18%), while stroke and lung fibrosis occurred in one patient each. Concomitant diseases were arterial hypertension in five patients (19%), coronary heart disease in two (7%) and aseptic osteonecrosis in two (7%). The mean number of American Rheumatism Association criteria met was 5.6±1.4 (range 4–8). Disease activity in 1991 was quantified using the scoring system of Valentijn et al. [28], which was the method employed by our group when our studies on SLE started in 1985. The Valentijn scoring system evaluates SLE activity as inactive, moderate or highly active. The mean Valentijn score was 4.4±2.8 (range 0–9), higher numbers indicating greater disease activity.

All patients were given a standardized clinical examination. Urinary, haematological and immunological tests were performed in the hospital's routine laboratory. aCL IgG and IgM antibodies were analysed with a commercial enzyme‐linked immunosorbent assay according to the manufacturer (Shield, Dundee, UK). Values above 30 GPL (IgG phospholipid units) and 30 MPL (IgM phospholipid units) U/ml were considered positive.

As the basis for comparison of neuropsychological performance, we used normative data for healthy subjects matched for age and education [29]. Previous studies have demonstrated no significant differences between American and Norwegian healthy controls and brain‐injured patients matched for age and education [30].

Neuropsychological examinations

These were performed at baseline (1991) and 5 yr later. A battery of standardized tests was used to measure different areas of cognition, such as attention, concentration, cognitive speed, executive function/abstract problem‐solving and motor function, as shown in Table 1. The patients were tested individually by an experienced and highly trained test technician. The examinations were based on the following tests: Similarities, Digit Span and Block Design subtests from the Wechsler Adult Intelligence Scale (WAIS) [31], parts A and B of the Trail Making Test, the Seashore Rhythm Test, the Category Test from the Halstead–Reitan neuropsychological test battery [32] the and Grooved Pegboard Test from the Kløve–Matthew motor steadiness battery [32]. T scores were calculated using published means and standard deviations for normative samples [29]. Standardized T scores have a mean of 50 and a standard deviation of 10. To reduce the statistical effects of regression to the mean, the difference from the start to the end of the study (change from baseline) was calculated for each individual neuropsychological variable, and the relative change from baseline, calculated as the percentage change, was used instead of the absolute value. This study treated neuropsychological measures as continuous variables and we therefore used raw scores in the calculation of relative changes. The influence of baseline values on subsequent changes in the individual cognitive variables after 5 yr of study were evaluated by regression analysis with baseline as the independent variable and percentage of change from baseline as the dependent variable.

Table 1. 

Neuropsychological domains and tests

Domain
 
Test
 
Simple attention Digit Span (WAIS) 
Complex attention Seashore Rhythm Test 
 Trail Making Test, part B 
Psychomotor function (speed) Trail Making Test, part A 
Executive function/abstract Category Test 
   problem‐solving  
Motor function (speed) Grooved Pegboard Test 
Intellectual functions  
   Verbal function Similarities (WAIS) 
    (reasoning/problem solving)  
   Non‐verbal function Block Design (WAIS) 
    (visual–spatial processing)  
Domain
 
Test
 
Simple attention Digit Span (WAIS) 
Complex attention Seashore Rhythm Test 
 Trail Making Test, part B 
Psychomotor function (speed) Trail Making Test, part A 
Executive function/abstract Category Test 
   problem‐solving  
Motor function (speed) Grooved Pegboard Test 
Intellectual functions  
   Verbal function Similarities (WAIS) 
    (reasoning/problem solving)  
   Non‐verbal function Block Design (WAIS) 
    (visual–spatial processing)  

WAIS, Wechsler Adult Intelligence Scale.

Statistical analysis

Results are presented as the mean and standard deviation. The two‐tailed paired t‐test or analysis of variance (ANOVA) was used to test differences between two or more groups of quantitative data. Group changes in test performance between the start and end of the study were examined with paired t‐tests. A statistical problem arises with multiple significance testing because the probability of finding a significant difference increases with increasing number of variables analysed (type I error). This can be corrected by the Bonferroni method, although with numbers of variables exceeding 4–5 this will be a conservative method, erring on the side of safety (non‐significance; type II error). In applying this to the extreme case, supposing all variables in this study were independent (n=9), the significance level would be 0.05:9≈0.006. However, within each test battery it may be assumed that the variables are more or less dependent on each other; the number of variables will then be 0.05:2≈0.03. There is no exact solution to this problem, but it is reasonable to assume that the significance level will be somewhere between these values. Because of the multiple comparisons, the Bonferroni‐corrected significance threshold of P<0.01 was considered appropriate to reduce the risk of type I errors.

Simple and multiple regression were used to analyse quantitative factors associated with change from baseline neuropsychological variables, while repeated measures ANOVA was used for qualitative factors.

Results

Analysis of dropouts

Of the original 36 patients, there were 8 drop‐outs. Six were dead, and two did not meet for follow‐up examination. No deaths, except one resulting from aneurysmal subarachnoid haemorrhage, were due to cerebrovascular disease that might have influenced the study outcome. There were no significant differences between patients who completed the study and dropouts in age, years of education, disease activity, months on corticosteroid medication, haematological parameters, immunological tests and individual cognitive test scores at the start of the study. Hence, participation bias for the patients who underwent a second assessment was not apparent.

Study group at the start and end of the study

The neuropsychological test results using T scores at the start and end of the study (baseline and follow‐up assessments) of the 28 SLE patients revealed no significant group changes in seven of nine cognitive variables (78%), while there were significant group improvements in test performance on two variables (22%) after 5 yr. These were the Trail Making Test parts A and B from the Halstead–Reitan neuropsychological test battery and a trend for Block Design from the WAIS (P=0.01), with the best test results at follow‐up (Table 2). Calculation using raw scores demonstrated no significant improvement except for a trend to improvement in the Grooved Pegboard Test (P=0.01).

Table 2. 

Neuropsychological function in 28 patients with SLE at baseline (1991) and follow‐up (1996): assessments using T scores

 1991
 

 
1996
 

 
 
Test
 
Mean
 
s.d.
 
Mean
 
s.d.
 
P
 
WAIS      
   Digit Span 44.5 6.7 44.4 8.0   0.9 
   Similarities 48.3 10.1 51.0 12.3   0.3 
   Block Design 47.4 8.5 52.9 11.0   0.01 
Halstead–Reitan neuropsychological test battery      
   Trail Making Test part A 37.2 6.5 47.6 10.3 <0.0001 
   Trail Making Test part B 46.4 6.7 50.4 6.9   0.006 
   Category Test 43.8 8.0 45.3 10.1   0.5 
   Seashore Rhythm Test 44.2 9.5 47.5 9.6   0.05 
   Grooved Pegboard Test, 40.6 10.4 40.6 9.5   0.9 
    dominant hand      
   Grooved Pegboard Test, 39.7 8.6 41.4 8.8   0.4 
    non‐dominant hand      
 1991
 

 
1996
 

 
 
Test
 
Mean
 
s.d.
 
Mean
 
s.d.
 
P
 
WAIS      
   Digit Span 44.5 6.7 44.4 8.0   0.9 
   Similarities 48.3 10.1 51.0 12.3   0.3 
   Block Design 47.4 8.5 52.9 11.0   0.01 
Halstead–Reitan neuropsychological test battery      
   Trail Making Test part A 37.2 6.5 47.6 10.3 <0.0001 
   Trail Making Test part B 46.4 6.7 50.4 6.9   0.006 
   Category Test 43.8 8.0 45.3 10.1   0.5 
   Seashore Rhythm Test 44.2 9.5 47.5 9.6   0.05 
   Grooved Pegboard Test, 40.6 10.4 40.6 9.5   0.9 
    dominant hand      
   Grooved Pegboard Test, 39.7 8.6 41.4 8.8   0.4 
    non‐dominant hand      

WAIS, Wechsler Adult Intelligence Scale.

Change from baseline

Using raw scores, the relative changes (as percentages) from the start of the study were calculated for each individual neuropsychological variable. This showed that changes were not dependent on baseline levels for most variables. However, there was a trend to significance for the Category Test, the Seashore Rhythm Test and the Grooved Pegboard Test, non‐dominant hand (P<0.05) (Table 3). For these three variables, a negative regression coefficient indicates that variables with high baseline values would have lower values at the end of the study, and variables with low baseline values would have higher values at the end of the study.

Table 3. 

Neuropsychological function in 28 patients with SLE: influence of baseline cognitive variables for subsequent change in cognitive parameters during 5 yr of observation

   Regression  
Test
 
R2
 
RSD
 
coefficient
 
P
 
WAIS     
   Digit Span   0.06 26.8 −3.33 0.23 
   Similarities   0.05 33.8 −3.47 0.24 
   Block Design   0.004 26.2 −0.76 0.74 
Halstead–Reitan neuropsychological test battery     
   Trail Making Test part A <0.001 30.4 −0.007 0.99 
   Trail Making Test part B   0.007 27.1 0.08 0.68 
   Category Test   0.21 41.2 −1.12 0.03 
   Seashore Rhythm Test   0.16 10.9 −1.43 0.02 
   Grooved Pegboard Test,   0.02 19.2 −0.27 0.46 
    dominant hand     
   Grooved Pegboard Test,   0.18 22.0 −0.97 0.03 
    non‐dominant hand     
   Regression  
Test
 
R2
 
RSD
 
coefficient
 
P
 
WAIS     
   Digit Span   0.06 26.8 −3.33 0.23 
   Similarities   0.05 33.8 −3.47 0.24 
   Block Design   0.004 26.2 −0.76 0.74 
Halstead–Reitan neuropsychological test battery     
   Trail Making Test part A <0.001 30.4 −0.007 0.99 
   Trail Making Test part B   0.007 27.1 0.08 0.68 
   Category Test   0.21 41.2 −1.12 0.03 
   Seashore Rhythm Test   0.16 10.9 −1.43 0.02 
   Grooved Pegboard Test,   0.02 19.2 −0.27 0.46 
    dominant hand     
   Grooved Pegboard Test,   0.18 22.0 −0.97 0.03 
    non‐dominant hand     

All scores are raw scores.

RSD, residual standard deviation.

WAIS, Wechsler Adult Intelligence Scale.

Cognitive changes and demographic or disease‐associated factors

Nine patients (32%) had a positive test result for aCL antibodies. No quantitative demographic or disease‐associated factor had a significant influence on the change from baseline of neuropsychological variables, except for months on corticosteroid medication, which was significantly associated with percentage change from baseline in the Grooved Pegboard Test, non‐dominant hand (y=−1.23+0.16x; R2=0.26; P=0.006). Inspection of the regression plot from the statistical analysis revealed one outlying extreme value that could have influenced the results of the analysis. When the patient responsible for this value, who had a cortical infarct in right hemisphere, was removed from the statistical analysis, this association disappeared.

Repeated measures ANOVA

No significant effect of demographic or disease‐associated parameters, including medication for SLE and aCL antibody, on neuropsychological measures was seen over time.

Discussion

The major objective of this study was to measure cognitive functioning over time in SLE patients. On a group basis, most neuropsychological variables were unchanged after 5 yr.

As SLE is a chronic autoimmune disease, one could assume that when NPSLE develops it will persist or lead gradually to more severe CNS manifestations and a decline in cognitive functions. This raises the concern that if cognitive defects evolve into more profound CNS dysfunction over time, the use of aggressive therapy should be considered. The real clinical picture appears to be more complex, however. Our results indicate that, in the majority of SLE patients, cognitive dysfunction is not cumulative over time, as their test performance indicates more or less stable neuropsychological dysfunction. Some of the variables actually changed in the direction of cognitive improvement during the observation period. This is an unexpected finding that can hardly be explained by the natural course of NPSLE. One possible explanation is methodological. The normative data used in this study were grouped into age intervals of 5 yr [29]. The SLE patient group, which had a mean age at baseline of 41.0 yr, was compared with a normal control group aged 40–44 yr. At follow‐up, the SLE patient group was compared with another normal group (45–49 yr). The improvement that was demonstrated may thus have been biased by this change of comparison norm, and the improvement may reflect a scaling effect of the T scores. Indeed, calculation using raw scores showed no significant improvement. Taken together, these results are consistent with stable cognitive dysfunction over time in SLE patients. This is in agreement with a recent study indicating relatively stable cognitive dysfunction [25], but contrasts with another longitudinal study that showed fluctuations in cognitive functions over time [23, 26].

Another approach is to investigate, in the individual patient, whether the level of functioning at the first examination is of importance for the subsequent development of cognitive dysfunction, or whether demographic or disease‐associated quantitative factors exert such an effect. We found that such changes over time were not significantly dependent on baseline values.

Most of the patients had a mild cognitive dysfunction and, on a group basis, several neuropsychological variables were within the normal range. However, in the individual patient some disease factors may be related to cognitive abnormalities. We recently reported that cerebral infarcts and cortical atrophy, as detected by cerebral computed tomography and magnetic resonance imaging, are the only features of SLE that are significantly associated with cognitive disturbances [17, 33].

No other demographic or disease‐associated factors, including immunological parameters that could predict changes in cognitive variables over time, were found. In particular, no relationship was found between the presence of aCL antibody and cognitive dysfunction. Our results contrast with two recently published longitudinal studies that have demonstrated an association between a persistently elevated aCL antibody titre and cognitive dysfunction in SLE [19, 20]. However, other studies have not been able to demonstrate such an association [16, 17]. More prospective observations are warranted.

One problem with measuring changes in cognitive function over time is to determine if a difference in test performance is real or represents chance variation or practice effects. The latter will vary as a function of test–retest intervals and, to a certain extent, variables such as age and education [34, 35]. For example, Hanly et al. [23] observed some improvement in performance on comparable neuropsychological tests in SLE patients and controls due to the practice effect when the interval between assessments was 1 yr, which could have biased the apparent improvement in performance over time, and this was their main finding. In our study, the SLE patients were followed up after more than 60 months, and test–retest effects should thus have been avoided.

In summary, cognitive dysfunction seems to be a relatively consistent and stable finding in SLE, possibly reflecting chronic neuronal damage. The present study demonstrates that, in the majority of patients, cognitive function did not deteriorate over a period of 5 yr. No associations with demographic factors, medication or other diseases were found.

Correspondence to: K. Waterloo, Department of Neurology, University Hospital, N‐9038 Tromsø, Norway.

The authors would like to thank Dr Bjørn Straume for statistical advice. We also thank Kari Bjerkås for assistance with neuropsychological examinations. RO was supported as a postdoctoral research fellow for Science and the Humanities by the Norwegian Research Council and also received support from the Norwegian Foundation for Health and Rehabilitation. ELISA tests for IgG and IgM aCL antibodies were performed at the Department of Immunology and Transfusion Medicine, University Hospital of Tromsø.

References

1
ACR ad hoc Committee on Neuropsychiatric Lupus Nomenclature.
Arthritis Rheum
 
1999
;
42
:
599
–608.
2
Estes D, Christian CL. The natural history of systemic lupus erythematosus by prospective analysis.
Medicine
 
1971
;
50
:
85
–95.
3
Abel T, Gladman DD, Urowitz MB. Neuropsychiatric lupus.
J Rheumatol
 
1980
;
7
:
325
–33.
4
McCune WJ, Golbus J. Neuropsychiatric lupus.
Rheum Dis Clin North Am
 
1988
;
14
:
149
–67.
5
Omdal R, Selseth B, Kløw NE, Husby G, Mellgren SI. Clinical neurological, electrophysiological, and cerebral CT scan findings in systemic lupus erythematosus.
Scand J Rheumatol
 
1989
;
18
:
283
–9.
6
Futrell N, Schultz LR, Millikan C. Central nervous system disease in patients with systemic lupus erythematosus.
Neurology
 
1992
;
42
:
1649
–57.
7
Tola MR, Granieri E, Caniatti L et al. Systemic lupus erythematosus presenting with neurological disorders.
J Neurol
 
1992
;
239
:
61
–4.
8
Wecking EM. Psychiatric symptoms in systemic lupus erythematosus: an update.
Psychosom Med
 
1993
;
55
:
219
–28.
9
Devinsky OD, Petito CK, Alonso DR. Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura.
Ann Neurol
 
1988
;
23
:
380
–4.
10
Hanly JG, Walsh NM, Sangalang V. Brain pathology in systemic lupus erythematosus.
J Rheumatol
 
1992
;
19
:
732
–41.
11
Denburg JA, Behmann SA. Lymphocyte and neuronal antigens in neuropsychiatric lupus.
Ann Rheum Dis
 
1994
;
53
:
304
–8.
12
Denburg JA, Carbotte RM, Denburg SD. Neuronal antibodies and cognitive function in systemic lupus erythematosus.
Neurology
 
1987
;
37
:
464
–7.
13
Long AA, Denburg SD, Carbotte RM, Singal DP Denburg JA. Serum lymphocytotoxic antibodies and neurocognitive function in SLE.
Ann Rheum Dis
 
1990
;
49
:
249
–52.
14
Maeshima E, Yamada Y, Yukawa S, Nomoto H. Higher cortical dysfunction, antiphospholipid antibodies and neuroradiological examinations in systemic lupus erythematosus.
Intern Med
 
1992
;
31
:
1169
–74.
15
Denburg SD, Carbotte RM, Ginsberg JS, Denburg JA. The relationship of antiphospholipid antibodies to cognitive function in patients with systemic lupus erythematosus.
J Int Neuropsychol Soc
 
1997
;
3
:
377
–86.
16
Hanly JG, Walsh NM, Fisk JD et al. Cognitive impairment and autoantibodies in systemic lupus erythematosus.
Br J Rheumatol
 
1993
;
32
:
291
–6.
17
Waterloo K, Omdal R, Jacobsen EA et al. Cerebral computed tomography and electroencephalography compared with neuropsychological findings in systemic lupus erythematosus.
J Neurol
 
1999
;
246
:
706
–11.
18
Waterloo K, Omdal R, Mellgren SI, Husby G. Neuropsychological functions in systemic lupus erythematosus: a comparison with chronic whiplash patients.
Eur J Neurol
 
1997
;
4
:
171
–7.
19
Hanly JG, Hong C, Smith S, Fisk JD. A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus.
Arthritis Rheum
 
1999
;
42
:
728
–34.
20
Menon S, Jameson‐Shortall E, Newman SP, Hall‐Craggs MR, Chinn R, Isenberg DA. A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus.
Arthritis Rheum
 
1999
;
42
:
735
–41.
21
Carbotte RM, Denburg SD, Singal DP, Denburg JA. Prevalence of cognitive impairment in patients with systemic lupus erythematosus.
J Nerv Ment Dis
 
1986
;
174
:
357
–64.
22
Ginsburg KS, Wright EA, Larson MG et al. A controlled study of the prevalence in randomly selected patients with systemic lupus erythematosus.
Arthritis Rheum
 
1992
;
35
:
776
–82.
23
Hanly JG, Fisk JD, Sherwood G, Eastwood B. Clinical course of cognitive dysfunction in systemic lupus erythematosus.
J Rheumatol
 
1994
;
21
:
1825
–31.
24
Hay EM, Huddy A, Black D et al. A prospective study of psychiatric disorder and cognitive function in systemic lupus erythematosus.
Ann Rheum Dis
 
1994
;
53
:
298
–303.
25
Carlomagno S, Migliaresi S, Ambrosone L, Sannino M, Sanges G, Di Iorio G. Cognitive impairment in systemic lupus erythematosus: a follow‐up study.
J Neurol
 
2000
;
247
:
273
–9.
26
Hanly JG, Cassell K, Fisk JD. Cognitive function in systemic lupus erythematosus: results of a 5‐year prospective study.
Arthritis Rheum
 
1997
;
40
:
1542
–3.
27
Tan EM, Cohen AS, Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus.
Arthritis Rheum
 
1982
;
25
:
1271
–2.
28
Valentijn RM, van Overhagen H, Hazevoet HM et al. The value of complement and immune complex determinations in monitoring disease activity in patients with systemic lupus erythematosus.
Arthritis Rheum
 
1985
;
28
:
904
–13.
29
Heaton RK, Grant I, Matthews CG. Comprehensive norms for an expanded Halstead–Reitan battery.
Odessa: Psychological Assessment Resources
  (PAR), FL,
1991
.
30
Kløve H. Validation studies in adult clinical neuropsychology. In: Reitan RM, Davidson LA, eds.
Clinical neuropsychology: current status and applications
 . New York: Hemisphere,
1974
, pp. 211–35.
31
Wechsler D. Wechsler Adult Intelligence Scale. New York:
Psychological Corporation
 ,
1955
.
32
Reitan RM, Davidson LA.
Clinical neuropsychology: current status and applications
 . New York: Hemisphere,
1974
.
33
Waterloo K, Omdal O, Sjöholm H et al. Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.
J Neurol
 
2001
;
248
:
595
–602.
34
Lezak MD.
Neuropsychological assessment
 . 3rd edn. New York: Oxford University Press,
1995
.
35
Dikmen SS, Heaton RK, Grant I, Temkin NR. Test–retest reliability and practice effects of expanded Halstead–Reitan neuropsychological test battery.
J Int Neuropsychol Soc
 
1999
;
5
:
346
–56.

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