The presence of executive functioning deficits may moderate the response to treatment, and metacognitive strategy training may IDH mutation need to be incorporated in these interventions. Finally, there is evidence from numerous studies indicating

that cognitive rehabilitation is effective during the postacute period, even many years after the initial injury. Additional research is needed to investigate the patient characteristics that influence treatment effectiveness. In our initial review, we indicated that cognitive rehabilitation should be directed at achieving changes that improve persons’ functioning in areas of relevance to their everyday lives. The majority of studies have relied on changes in cognitive functioning, assessed by standardized neuropsychologic

testing or other cognitive measures, as proximal outcomes of cognitive rehabilitation. Our reviews are consistent with the view that cognitive rehabilitation Trametinib is effective in helping patients learn and apply compensations for residual cognitive limitations, although several studies suggest that intervention may directly improve underlying cognitive functions.10, 15 and 99 Our systematic reviews provide more limited evidence regarding improvements at the level of functional activities, participation, or life satisfaction after cognitive rehabilitation. Although improvements at the level of social participation and quality of life are valued as the distal health-related outcomes of cognitive rehabilitation, it is often not possible to observe improvements on these more global outcomes within

the limited timeframes used in most investigations of cognitive Amino acid rehabilitation. The possible reasons for this include the relatively brief periods of intervention, limited opportunity to address the application of interventions to everyday functioning, lack of follow-up assessing community functioning, or failure to include the relevant outcome measures. A number of studies have evaluated treatment effects based on observations of everyday functioning or performance on tasks derived from activities of daily living, which provide evidence for the effects on daily functioning. Studies of comprehensive-holistic cognitive rehabilitation provide the best evidence for improvements in health-related outcomes, such as social participation and quality of life. Since our prior reviews, more sophisticated criteria have been developed for evaluating the level of evidence beyond basic study design (eg, blinding of outcome assessments). We recognize that the failure to employ these additional criteria has influenced the classification of studies and is a limitation of this review. We elected to retain our initial criteria in order to be consistent with our prior reviews.