Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning

We designed a study to assess the specific contribution of cognitive dysfunction to multiple sclerosis patients' problems in daily living. Based on the results of a comprehensive neuropsychological test battery, we classified 100 MS patients as either cognitively intact (N = 52) or cognitively impaired (N = 48). In addition to a neurologic examination, MS patients completed questionnaires on mood and social functioning, underwent a comprehensive in-home occupational therapy evaluation, and were rated by a close relative or friend regarding specific personality characteristics. While there were no significant differences between the two groups on measures of physical disability and illness duration, patients in the cognitively impaired group were less likely to be working, engaged in fewer social and avocational activities, reported more sexual dysfunction, experienced greater difficulty in performing routine household tasks, and exhibited more psychopathology than cognitively intact patients. These findings suggest that cognitive dysfunction is a major factor in determining the quality of life of patients with MS.     

Cognition in the early stage of multiple sclerosis

Objective Cognitive dysfunctions may contribute to limitation of everyday activities of patients with multiple sclerosis (MS). Recent studies have demonstrated that 45 to 65% of MS-patients are cognitively impaired. The profile of MS-related cognitive dysfunctions varies greatly. It includes memory and learning deficits, attention deficits, executive dysfunctions and visuo-spatial deficits. Most studies of cognition in MS examined patients in later stages, often including MS-patients with marked physical disabilities. Studies of cognitive dysfunctions in the early stage of the disease are rare. This study specifically aimed at evaluating and characterizing cognitive impairments in the early stage of MS, and determining specific patterns of cognitive dysfunction. Methods 21 MS patients, experiencing their first neurological symptoms not more than two years previously, and 22 healthy controls were compared. A comprehensive neuropsychological test-battery was used to evaluate MS-related cognition. The battery consisted of memory and learning tests, executive functioning tests and a visuo spatial functioning test. A computerized attention test-battery was also included, which assess accuracy and speed of test responses. In addition depression and intellectual capabilities were assessed. Results Compared with healthy controls, MS-patients in the early stage of the disease performed significantly lower on each neuropsychological assessment, except for verbal short-term memory. In particular, MS-patients showed a lengthened reaction time for simple and focused attention (19–38%), impaired non-verbal memory function (RVDLT recognition: 33%) and a planning deficit (24%). Associations between information processing speed and disease course and the employment situation were additionally found. However, patients did not have clinically relevant depression rates on the ADS-L and visuo spatial abilities remain preserved. Conclusion Our findings revealed discrete cognitive dysfunction in MS-patients within the early stage of the disease. Received in revised form: 18 January 2006     

Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) in the Italian population

Cognitive dysfunction involves 40–65 % of multiple sclerosis (MS) patients. It can be detected in all MS phenotypes from the early stages of the disease, and it tends to progress over time. Minimal Assessment of Cognitive Function in MS (MACFIMS) has been proved to be the most sensitive and comprehensive battery available for MS cognitive assessment in the English population. In Italy, MACFIMS applicability is limited in everyday clinical practice since the overall validity of this battery in the Italian MS population has never been demonstrated. The aim of this study was to translate/cross-culturally adapt and validate an Italian version of the MACFIMS. A total of 130 MS patients and 60 healthy controls (HCs) were enrolled and evaluated with an Italian version of the MACFIMS. All tests discriminated MS patients from HCs; according to the literature, approximately more than half of MS patients (70.8 %) exhibit cognitive impairment. Principal component analysis showed four distinct components: visual–spatial memory/processing speed, working memory, executive functions and verbal memory. Our study is the first to validate an Italian version of the MACFIMS. Several aspects of validity have been demonstrated: criterion and, partially, construct. Future work will investigate the longitudinal course of neuropsychological dysfunction in Italian MS patients using these measures.     

Differential patterns of memory performance in relapsing, remitting and secondary progressive multiple sclerosis

BACKGROUND: Memory dysfunction is common in multiple sclerosis (MS). A retrieval failure has been reported as the primary cause for the memory deficits, although some studies also described a faulty acquisition. AIMS: The aim of the study was to examine memory function in relapsing remitting (RR) and secondary progressive (SP) MS patients, analyze the patterns of performance and to investigate whether disease course influences this performance. DESIGN AND SETTINGS: Case-control prospective study conducted in a clinical setting. MATERIALS AND METHODS: Fifty-five RR, 23 SP MS patients and 80 normal subjects were evaluated with a comprehensive neuropsychological battery. Memory was assessed with tasks from the Signoret memory battery. Attention and executive function were also assessed. STATISTICAL ANALYSIS: Univariate analysis of variance, Mann-Whitney U-test, multivariate logistic regression and Chi-square test were used as appropriate. RESULTS: MS patients performed significantly worse than controls on almost all measures of memory (P < 0,001). MS subgroups differed in tasks of delayed recall (logical memory- P =0,019; wordlist delayed recall, P < 0,001), semantic cued recall (P < 0,001), recognition trials (P =0,006) rate of forgetting (P < 0,001) and confabulation and intrusion errors (P =0,004). CONCLUSIONS: Memory is consistently impaired in MS patients and disease course differentially affects the pattern of performance. SP patients show greater difficulties and a more pervasive pattern of dysfunction than RR patients. Delayed recall was the most affected memory measure and performance on this task discriminates between RR and SP MS patients. Relapsing remitting patients performed within the mildly impaired range while SP patients showed a moderate to severe impairment.     

A 3-year longitudinal study of cognitive impairment in patients with primary progressive multiple sclerosis: speed matters

BACKGROUND: The few controlled longitudinal studies of cognitive performance in MS patients all provide evidence of deterioration in at least a subset of the patients sampled. Only one of these studies has focused on primary progressive MS, and little attention has been paid to the specific domains of cognitive functioning that change over time. The present study examined three principal cognitive domains in samples of primary progressive MS patients and healthy controls followed over a period of 3 years. METHODS: A battery of neuropsychological tests that included measures of strategic problem solving, verbal memory, and information processing speed was administered annually to 24 MS patients and 25 controls. RESULTS: MS patients' performance on measures of processing speed showed significantly greater decline over the 3-year period than did that of controls. Similar results were not observed in the case of problem solving or verbal memory. There was no evidence of more dramatic decline occurring in patients who were initially classified as cognitively impaired relative to those who were unimpaired at baseline. However, this failure may have been influenced by differential attrition from the sample; more impaired patients were less likely to complete the study. CONCLUSION: Overall the results support the contention that information processing speed is the domain most sensitive to the impact of multiple sclerosis on cognitive functioning over time.     

Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.     

Memory deficits and early cognitive deterioration in MS

Introduction – In the present study, the pattern of memory and learning deficits in two cognitively different, but clinically and demographically similar, multiple sclerosis (MS) groups was compared. Material & methods – 23 patients represented the cognitively preserved MS group and 22 patients the MS group with early cognitive decline. A control group of 35 healthy controls was also included. The cognitive status of the subjects was defined using the Mild Deterioration Battery (MDB). Furthermore, all subjects were given a set of memory and learning tests and were instructed to evaluate the frequency of their memory and learning difficulties. The Mini-Mental State Examination (MMSE) was also administered to all subjects. Results – The cognitively deteriorated patients, even those with normal MMSE performance, showed widespread memory and learning deficits, but adequate self-evaluation of their everyday memory and learning difficulties. The preserved group, in turn, performed similarly to the controls. Conclusion – Widespread memory and learning deficits are associated with relatively mild cognitive decline in MS. These deficits were observable in the intermediate-length screening battery, the MDB, but not in the MMSE. The present study suggests that the accuracy of patients'own evaluations of their memory and other cognitive problems is superior to the results of very brief screening batteries, like the MMSE. Therefore, brief screening in neuropsychological assessment of MS patients is not recommendable.     

Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients.     

Cognitive impairment in relapsing and primary progressive multiple sclerosis: mostly a matter of speed.

Based on the assumption that cognitive impairment in MS is consistent with subcortical dementia, a battery of neuropsychological tests was assembled that included measures of executive function (Tower of London and Wisconsin Card Sorting Test), verbal learning and memory (a paired associates learning test), and speeded information processing (Stroop Color Word Interference Test). The battery was administered to patients with relapsing and primary progressive MS and to healthy controls. Differences between patients and controls occurred on several of the measures. However, when differences with respect to fatigue and depression were statistically controlled, the only differences that remained significant involved measures relating to the speed of information processing. Patients performed more slowly than controls, with the disparity being greater for relapsing patients than for those with primary progressive disease. The slowing was evident on measures of automatic as well as controlled processing and regardless of whether speed was an explicit feature of successful performance or recorded unobstrusively while the patient concentrated on planning a correct solution to a problem. Parallels were noted between cognitive slowing associated with MS and that of normal aging.     

Cognitive impairment in primary and secondary progressive multiple sclerosis

The aim of this study was to use neuropsychological data to characterize two subtypes of multiple sclerosis (MS) patients in a large patient sample. We studied patients with primary-progressive MS (PPMS) and secondary-progressive MS (SPMS). A group of 121 MS patients (36 PPS, 85 SPMS) and 40 healthy controls were administered a brief battery of cognitive tests. Executive functioning, memory and attention were studied. Results demonstrate that PPMS patients exhibited slightly more impairment than patients with SPMS, although this difference is not significant (50% vs 37%). However, PPMS patients revealed a significantly poorer performance in verbal learning (p < 0.05) and in verbal fluency (p < 0.05). Whereas PPMS patients had significantly shorter disease durations (p < 0.05), there was no statistical difference in disability between both groups. We conclude from our study that cognitive deficits in progressive MS are frequent. Patients with PPMS tend to be more frequently and severely affected than SPMS patients. Our findings of high prevalence of cognitive involvement in PPMS have not been reported previously     

The use of amnestic and nonamnestic composite measures at different thresholds in the neuropsychological diagnosis of MCI

Both amnestic and nonamnestic deficits have been observed in patients with mild cognitive impairment (MCI). Most studies have focused on impairment on single cognitive tests rather than amalgamation of the results of several measures to arrive at a composite impairment index. In this investigation, we examined 20 MCI patients diagnosed as prodromal Alzheimer's disease, AD (mean Mini-Mental State Examination, MMSE = 26.1; SD = 1.7) and determined the extent to which they could be differentiated from 70 normal elderly controls based on composite measures at 1.5-SD and 2.0-SD cutoffs for impairment. At the 1.5-SD cutoff, the median number of memory indices impaired in the MCI-AD group was 5 of 7, whereas at the 2.0-SD cutoff, the median number was 4 of 7. A median of 3 of 7 and 2 of 7 nonmemory indices were impaired at 1.5- and 2.0-SD cutoffs for impairment. Receiver operator characteristics (ROC) analyses indicated that the total number of memory tests impaired at 2.0 SD (sensitivity = 95.0%/specificity = 84.3%) and the composite measure of both impaired memory and nonmemory measures (sensitivity of 85.0%/specificity of 100%) had high levels of discrimination and may have utility as indices of early impairment as well as severity of MCI.     

Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire

Since there is a need for cost-effective screening techniques to identify neuropsychological impairment in multiple sclerosis (MS) patients, and because existing methods require cognitive testing with subsequent interpretation by a neuropsychologist, a brief self-report procedure was developed to screen for neuropsychological impairment in MS. In the first phase of the study, a pool of 80 items was generated based on a literature review and consultation with healthcare professionals. The set was reduced to 15 via Rasch analysis. Using these items, a brief (five minute) MS Neuropsychological Screening Questionnaire (MSNQ), including patient- and informant-report forms, was composed. In phase II, 50 MS patients and their caregivers completed the MSNQ. A comprehensive neuropsychological test battery was also administered. Analyses covered the reliability of the MSNQ and correlations between both patient- and informant-report scores and objective neuropsychological testing. Cronbach's alpha coefficients were 0.93 and 0.94 for the patient- and informant-report forms, respectively, and both forms of the test were strongly correlated with a more general cognitive complaints questionnaire. The patient MSNQ form correlated significantly with measures of depression but not with objective tests of cognitive function. In contrast, the informant form was correlated with patient cognitive performance but not depression. A cut-off score of 27 on the informant form of the MSNQ optimally separated patients based on a neuropsychological summary score encompassing measures of processing speed and memory. There were two false-negatives and one false-positive, giving the test a sensitivity of 0.83 and a specificity of 0.97. It is concluded, therefore, that this self-administered neuropsychological screening test is reliable and predicts neuropsychological impairment in MS patients with a reasonable degree of accuracy.     

Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status

Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients.     

A factor analytic investigation of the Mercy Evaluation of Multiple Sclerosis

Abstract

Objective: Neurocognitive deficits commonly are an accompanying feature of Multiple Sclerosis (MS). A brief, yet comprehensive neuropsychological battery is desirable for assessing the extent of these deficits. Therefore, the present study examined the validity of the Mercy Evaluation of Multiple Sclerosis (MEMS) for use with the MS population. Methods: Archival data from individuals diagnosed with MS (N = 378) by independent neurologists was examined. Cognitive domains assessed included processing speed and attention, learning, and memory, visuospatial, language, and executive functioning. A mean battery index was calculated to provide a general indicator of cognitive impairment within the current sample. Results: Overall performance across participants was found to be in the lower limits of the average range. Results of factor analytic statistical procedures yielded a four-factor solution, accounting for 67% of total variance within the MEMS. Four neurocognitive measures exhibited the highest sensitivity in detecting cognitive impairment, constituting a psychometrically established brief cognitive screening battery, which accounted for 83% of total variance within the mean battery index score. Conclusion: Overall, the results of the current study suggest appropriate construct validity of the MEMS for use with individuals with MS, as well as provide support for previously established cognitive batteries.     

Analysis of Impairment Related Functional Architecture in MS Patients during Performance of Different Attention Tasks

More than 50 % of patients with multiple sclerosis (MS) suffer from cognitive deficits. Attention is one of the most frequently affected cognitive functions. It has been shown that MS patients suffer from a specific but not necessarily from a generalized decrease in performance and that different severity grades of impaired attentional processing can be distinguished. Little is known about patterns of brain activation in MS patients with different grades of attentional deficits. The objective was to examine if different severity grades in attentional impairment are reflected by altered patterns of brain activation in specific attention tasks. In the present study cerebral activation induced by three attention tasks of different complexity was assessed in 14 MS patients and seven healthy controls by functional MRI (fMRI). Based on their performance on the tests recorded off-line with a computerized test battery and during the fMRI investigation, patients were classified as mildly and severely impaired. MS patients with mild impairment showed increased and additional activation of brain areas which were in part not activated in normal subjects. Those were located mainly in the frontal cortex and posterior parietal cortex. This effect decreased with increasing task complexity and was strongest for the alertness task. In MS patients with severe impairment no additional activation was found in prefrontal structures and activation in the premotor cortex was not significantly different from controls. These findings suggest that compensation in MS patients is in part achieved by functional integration of frontal and parietal association areas. The extent of compensation seems to depend on the brain's capacity to access additional brain structures. Exhaustion of this capacity may finally lead to severe cognitive impairment.     

Group and case study of the dysexecutive syndrome in alcoholism without amnesia

OBJECTIVES: To test the dysexecutive syndrome (DES) hypothesis of chronic alcoholism by the neuropsychological group and case study approaches. METHODS: A comprehensive neuropsychological assessment, including the "behavioural assessment of dysexecutive syndrome", a battery of tests recently designed to be "ecologically valid", was administered to 17 patients with chronic alcoholism without amnesia to examine executive functions, intelligence, and memory. In terms of each neuropsychological measure, reciprocal analyses of group means and individual case profiles were conducted: for the first contrasting the alcoholic patients with 17 age matched healthy subjects; and for the second making intersubject and intrasubject comparison of the patients, according to percentile basis impairment indices obtained from the control subjects. RESULTS: Despite relatively unimpaired memory and intelligence, the patients as a whole had the impairment of a wide range of executive domains, extending to "everyday" problem solving as well as more elementary aspects of executive functions, such as visuospatial performance, mental set shifting, and the inhibition of habitual behaviour. The profile analysis divided individual patients into four groups: the representative DES characterised by a clear dissociation between impaired executive functions and preserved intelligence and memory; the group of a modified dysexecutive pattern in which memory as well as executive functions were impaired with intelligence preserved; the group of general cognitive deterioration; and the group of unimpaired cognitive functioning. About two thirds of the patients were categorised into either the first or the second type of DES. CONCLUSION: DES characterised by the even more pronounced impairment of executive functions than of intelligence and memory afflicts a considerable proportion of patients with chronic alcoholism. Due to its subtlety, this would be potentially left out, unless appropriate behavioural measures were administered. This condition may prevent patients with alcoholism from achieving full recovery and benefiting from rehabilitation.     

Screening for cognitive impairment in multiple sclerosis using the Symbol digit Modalities Test

Cognitive impairment is common in multiple sclerosis (MS), yet difficult to detect during routine neurologic examination. Therefore, brief screening tests that identify patients who may benefit from a more thorough assessment or treatment are needed. We investigated the utility of the Symbol Digit Modalities Test (SDMT) as a screen for cognitive dysfunction because it can be administered and scored in about 5 minutes. One hundred MS patients and 50 healthy controls, matched on demographic variables, participated in the study. Examination procedures included the neuropsychological (NP) tests included in the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. Patients were considered impaired if they performed one and a half standard deviations below controls on two or more MACFIMS variables, excluding the SDMT. Bayesian statistics showed that a total score of 55 or lower on the SDMT accurately categorized 72% of patients, yielding sensitivity of 0.82, specificity of 0.60, positive predictive value (PPV) of 0.71, and negative predictive value (NPV) of 0.73. These results suggest that the effectiveness of the SDMT as a screen for cognitive impairment in MS is roughly equal to that of other psychometric and questionnaire methods.     

Neuropsychological function in obsessive-compulsive disorder: effects of comorbid conditions on task performance.

BACKGROUND: Neuropsychological testing reveals a pattern of impairment among patients with obsessive-compulsive disorder (OCD) which implicates the orbitofrontal region. Studies of neuropsychological function in OCD differ regarding performance deficits on classical tests of frontal executive function. In some studies, OCD patients did not demonstrate impaired performance on tests of executive function. However, other researchers have documented performance deficits among OCD patients on measures of executive function. Patients with OCD also exhibit performance deficits on tests of visual/spatial memory and verbal memory. Again, in some studies, OCD patients did not demonstrate impaired performance on tests of memory function. How can we account for the conflicting findings? One possibility is that performance deficits on tests of cognitive function are associated with comorbid conditions. In prior work, we observed that OCD patients who did poorly on executive function tasks obtained high scores on a measure of schizotypal personality. A second possibility is that executive function deficits among patients with OCD are associated with comorbid depressive symptoms. METHOD: In the present study, a comprehensive neuropsychological test battery was administered to patients with OCD and matched healthy control subjects. We also administered dimensional measures of schizotypal personality and depression to patients with OCD and controls. We conducted analyses of covariance (ANCOVA), with scores on measures of schizotypal personality and depression used as covariates. RESULTS: OCD patients demonstrated performance deficits on measures of delayed memory, response inhibition, alternation learning, and obtained significantly higher scores on measures of disinhibition, impulsivity, and temporolimbic symptoms; however, OCD patients did not exhibit impaired performance on tests of executive function and verbal fluency, and did not report a significantly greater number of dysexecutive symptoms, when coexistent depressive and schizotypal symptoms were taken into account. CONCLUSION: Findings are consistent with the contention that dysfunction of an orbitofrontal-limbic network underlies OCD.     

Cognitive phenotypes in temporal lobe epilepsy.

The objective of this study is to determine if distinct cognitive phenotypes could be identified in temporal lobe epilepsy. Epilepsy patients (n = 96) and healthy controls (n = 82) underwent comprehensive neuropsychological assessment. Adjusted (age, gender, and education) test scores for epilepsy subjects were grouped into cognitive domains (intelligence, language, visuoperception, immediate and delayed memory, executive function, and cognitive/psychomotor speed). Cluster analysis revealed three distinct cognitive profiles types: (1) minimally impaired (47% of subjects); (2) memory impaired (24%); and (3) memory, executive, and speed impaired (29%). The three cluster groups exhibited different patterns of results on demographic, clinical epilepsy, brain volumetrics, and cognitive course over a 4-year interval. The specific profile characteristics of the identified cognitive phenotypes are presented and their implications for the investigation of the neurobehavioral complications of epilepsy are discussed.     

Cognitive deficits early in the course of rheumatoid arthritis

Objective: The aim was to examine the severity and prevalence of cognitive difficulties in persons with rheumatoid arthritis (RA) within the first three years of diagnosis. Method: One hundred consecutive RA patients aged 28–67 years (90% women) were administered a battery of 6 neuropsychological tests yielding 14 cognitive indices. Self-reported measures of trait anxiety, depression, impact of disease on daily activities, and pain severity were also obtained along with physician-rated disease severity. Results: Twenty percent of RA patients were classified as cognitively impaired, defined as age- and education-adjusted scores at least 1.5 standard deviations below the population mean on 3 or more cognitive indices. Impaired performance, controlling for age, education, and premorbid cognitive capacity, was detected primarily on measures of short-term memory, immediate and delayed episodic recall, and phonemic fluency. There were modest negative associations between cognitive indices and measures of perceived disease severity (pain level, impact of disease on daily functionality, and overall health quality). Conclusions: Cognitive deficits on several domains are frequently encountered in relatively young RA patients during the first few years of the disease and may need to be taken into account as important correlates of disease severity and progression.