The primary goal of this meta-analysis involved the quantification of the overall magnitude of cognitive impairment in persons with RRMS compared with healthy controls. Indeed, one of the main findings was the overall moderate degree of impairment in cognitive functioning in those with RRMS. We further note that the individuals with RRMS demonstrated significant impairments compared with healthy controls across all domains of cognitive function. Our results extend the findings in the extant literature by providing a quantitative metric of the magnitude [87
] of cognitive problems in this population. Such findings further underscore that the degree of cognitive impairment in RRMS is not trivial, but rather moderate in magnitude. This is important as cognitive deficits interfere with everyday functioning and are associated with feelings of depression, low self-esteem and impaired social functioning [91
]. Therefore, there is a clear need for identifying strategies for mitigating cognitive impairment in RRMS.
The cognitive deficits in RRMS differed in magnitude based on the domain of cognitive function. The largest detriments in cognition were observed for motor functioning and mood status, followed by memory and learning, and attention and executive functioning. Motor functioning assessed through the grooved pegboard, finger tapping, nine-hole peg test was severely affected (g
= −0.728, P
< 0.05) and this is consistent with findings of a previous meta-analysis that included all types of MS [22
]. Such a finding is not surprising given the profound motor disturbances that are a defining feature of MS. The domain of mood status further demonstrated large cognitive deficits and the largest effect size was seen for measures of depression (g
= −0.701, P
< 0.05), although the QB
statistic was not significant for this domain and the effect of RRMS on depression was not significantly greater than the effect on anxiety. Such findings are particularly important for interventions designed to reduce cognitive deficits in this population by suggesting that emotional variables may either be influenced and/or influence the cognitive functioning of persons with RRMS. These results underscore the importance of investigating the efficacy of current psychotherapeutic approaches with this population as a target of both emotional and cognitive symptoms (See ref. [96
] for such an intervention).
An important goal for future research, as mentioned above will be to design intervention studies that simultaneously target cognitive and emotional symptoms experienced by patients with MS. In order to successfully design such studies, it is important to delineate variables that might affect or moderate the relationship between MS and cognition. In our search for such moderating variables, we found that age and gender of MS participants had a significant bearing on the relationship between MS and cognition. Although, at first we did not find either neurological disability or disease duration to significantly contribute to the variability in effect sizes, domain-specific analyses suggested that MS patients with an EDSS score of 4 or more and a disease duration of more than 10 years performed poorly on tasks of memory and learning. This finding thus suggests that when the effect sizes for different cognitive domains are averaged, neurological disability or disease duration fail to show an impact, however, for the domain of memory and learning, both of these variables impact performance. Given that this particular domain shows the largest effect sizes, the results are interesting in that they suggest that the disability progression in MS is rather divergent. In the meta-analysis of memory impairments in MS [6
], such a similar finding was noted for chronic-progressive MS course. This meta-analysis, which examines RRMS patients, provides evidence for the impact of clinical variables on the domain of memory and language.
In this meta-analysis, we were also interested in the sensitivity of the different measures used in the literature to assess declines in cognitive functioning. We found that the classic color-word Stroop task and measures of verbal fluency showed the largest effect sizes (g = −0.785 and g = −0.76, P < 0.05), suggesting that these measures might be more sensitive in detecting cognitive deficits as opposed to other measures. This finding is important as it suggests that these two measures, if included, in the brief neuropsychological batteries developed to assess neurocognitive functioning in patients with MS, would be more efficient at detecting subtle declines in cognitive functioning.
To summarize, the results of the current meta-analytic review suggest that the effects of MS on cognition is both general, such that all cognitive domains show a differential performance effect as well as specific, such that the effects are largest for the domains of mood, motor functioning and memory and learning. We further found evidence for the association between several demographic and clinical variables on selective aspects of cognition.