Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations

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Abstract

The prevalence and pattern of cognitive impairment in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23 NPSLE patients and 27 healthy controls were evaluated with a battery of standardized neuropsychological and psychological tests. Disease duration, disease activity index, and current corticosteroid therapy were collected. Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects with nSLE and NPSLE, respectively. Both SLE groups showed a significant impairment compared with controls on tasks assessing verbal and non-verbal long-term memory, and visuoconstructional abilities. In addition, NPSLE patients reported worse performances than both nSLE patients and controls on task evaluating short-term visuospatial memory. NPSLE subjects were significantly more anxious and depressed compared to both nSLE subjects and controls. By multivariate analysis, only depression levels, among clinical variables, significantly predicted cognitive performance. This study shows that cognitive impairment occurs frequently in both nSLE and NPSLE subjects. The higher frequency in NPSLE may be related to coexisting depressive disturbances.

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystemic involvement with a broad spectrum of clinical manifestations. Neurologic or psychiatric manifestations, or both during SLE, occur in up to two thirds of patients [1], [2]. Central nervous system (CNS) manifestations in SLE are very diverse, ranging from headache to severe life-threatening conditions [1], [2]. Recently, the American College of Rheumatology (ARA) Nomenclature for neuropsychiatric SLE (NPSLE) [3] provided case definitions for 19 neuropsychiatric syndromes in SLE, including the presence of cognitive dysfunction as a separate syndrome. The prevalence of cognitive dysfunction in SLE patients varies from 20% to 80% [4], [5], [6], [7], [8]. Although cognitive dysfunction in SLE patients is well-documented, the quantitative (i.e. prevalence of cognitive impairment) and qualitative (i.e. pattern of cognitive impairment) aspects of cognitive impairment in NPSLE subjects compared to non-neuropsychiatric patients (nSLE) remain unclear. Carbotte et al. [4] reported a higher significant prevalence of cognitive impairment in NPSLE subjects with respect to nSLE patients; however, other studies did not find significant differences between the two groups of patients [5], [8].

Regarding the pattern of cognitive impairment in SLE patients, a selective impairment was observed on measures of attention, verbal fluency, visuographic skills, immediate and delayed verbal and non verbal memory, and cognitive flexibility [8], [9].

Even in this case, the few data comparing the pattern of cognitive performances in nSLE vs. NPSLE patients are rather conflicting. Some authors [8], evidenced a substantial overlapping between the two groups of patients, while Denburg et al. [9] showed that NPSLE patients were significantly more impaired than nSLE subjects. This wide variation of findings about prevalence and pattern of cognitive impairment among reports might reflect differences in classification, case selection, and difficulties in classifying NPSLE [1], [2]. On the other hand, the possibility exists that the absence of a specific quantitative/qualitative ‘SLE-pattern’ of cognitive impairment reflects the clinical heterogeneity of NPSLE and the multiple underlying mechanisms [1], [2]. Attempts to reduce such heterogeneity have lead some authors to evaluate the relationship between cognitive impairment and such clinical variables including disease activity, disease duration, or corticosteroid treatment [4], [5], [6], [7], [8], [10], [11]. Most studies, although not all [5], [10], have demonstrated no association between cognitive impairment and such variables [4], [6], [7], [8], [11]. In fact, behavioral disturbances, which include depressed and/or anxious mood, have been repeatedly documented as the main factors influencing cognitive functioning in SLE patients [6], [7], [12]. However, most studies have not found association between behavioral and cognitive functioning in patients with and without neuropsychiatric involvement [4], [8], [9].

The present study was conducted to clarify issues regarding the prevalence and mechanisms of cognitive impairment in an unselected group of female SLE patients with or without neuropsychiatric manifestations. First, we compared cognitive functioning in nSLE and NPSLE patients vs. healthy control subjects similar for age, education, and social background, focusing our attention on the quantitative and qualitative features of cognition in the two groups of patients. In a second phase, we examined the relationship between cognitive impairment in nSLE and NPSLE subjects and such potential clinical predictive variables for cognitive impairment including neuropsychiatric involvement, disease duration, disease activity, current corticosteroid use, and levels of anxiety and depression.

Section snippets

Patients

We assessed 75 SLE female patients (52 with nSLE and 23 with NPSLE) seen consecutively over a 12-month period (from July 1998 to June 1999). They were seen as outpatients in the Immunologic Clinic at the Spedali Civili Hospital, Brescia, Italy. All patients fulfilled the revised 1982 American College of Rheumatology criteria for SLE [13]. The study was restricted to women to ensure a homogenous population and to facilitate interpretation of neuropsychological performance. Twenty-seven healthy

Results

Table 1 shows means and standard deviations of age, education, and levels of anxiety and depression for nSLE and NPSLE subjects and controls. It shows also clinical variables (disease duration, ECLAM index, and current prednisone use) between SLE groups. One-way ANOVAs did not showed significant group differences with regard to age and education. Concerning behavioral measures, significant differences were found between patients and controls on the HARS (F2,98=8.895, P<0.0003) and on the HDRS (F

Quantitative and qualitative features of cognition in nSLE vs. NPSLE subjects

Cognitive impairment occurs significantly more frequently in NPSLE patients than in nSLE subjects (52.2% vs. 26.9%) at the time of neuropsychological testing. Our data confirm previous data by Carbotte et al. [4] who found a prevalence of cognitive impairment in about 80% vs. 40% of NPSLE and nSLE subjects, respectively. In contrast with these and our data, other authors [5], [8] reported similar frequency of cognitive impairment in nSLE and NPSLE subjects. Regarding cognitive performances, the

Acknowledgements

R. Monastero was supported by a fellowship of the European Neurological Society. Most of all our thanks go to the patients and controls.

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