Improving New Learning and Memory in Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional

Summary: 
      The current study is a double-blind, placebo-control randomized clinical trial examining the
      efficacy of memory retraining in Multiple Sclerosis (MS). Impairment in higher level
      cognitive processing, such as new learning and memory, is one of the most common deficits in
      individuals with MS and such deficits have been shown to exert significant negative impact on
      multiple aspects of everyday life, including occupational and social functioning. Despite
      these findings, few studies have attempted to treat these cognitive deficits in order to
      improve the everyday functioning of individuals with MS. Through a small randomized clinical
      trial, we found that individuals with MS with documented memory impairment show a significant
      improvement in their memory performance following a treatment protocol designed to facilitate
      learning. The current proposal will replicate this finding and further evaluate (a) the
      impact of the treatment on everyday functioning, (b) the long term efficacy of the treatment
      and (c) the utility of booster sessions in facilitating long-term treatment effects. We will
      randomly assign individuals with MS, with documented impairment in new learning abilities, to
      a memory retraining group or a placebo control group. Both groups will undergo baseline,
      immediate and long-term follow-up assessment consisting of: (1) a traditional
      neuropsychological battery and (2) an assessment of global functioning examining the impact
      of the treatment on daily activities. This design will allow us to evaluate the efficacy of
      this particular memory retraining technique in an MS population through the assessment of
      cognitive function via a standard evaluation. In addition, we will be able to draw
      conclusions regarding the impact of this particular memory remediation program on everyday
      life from questionnaires completed by the participant and a significant other. Optional
      enrollment in pre- post neuroimaging will also allow us to look at changes in the brain.
    

Detailed description: 
      Impairments in higher level cognitive processing, such as new learning and memory, are among
      the most common deficits in individuals with Multiple Sclerosis (MS) and such deficits have
      been shown to exert significant negative impact on multiple aspects of everyday life,
      including occupational and social functioning. Despite these findings, few studies have
      attempted to remediate these cognitive deficits in order to improve the everyday functioning
      of individuals with MS. While limited research addressing the efficacy of memory retraining
      in MS does exist, this research has been marred by significant methodological flaws.
      Specifically, the only existing study of memory retraining in MS to utilize: (1) a randomized
      clinical trial and (2) an objective outcome assessment is our pilot research carried out at
      Kessler Medical Rehabilitation Research and Education Corporation (KMRREC).

      "The Advisory Board recommends that NCMRR initiate and coordinate studies of the
      effectiveness of medical rehabilitation interventions…using new and precise quantitative
      measurements of impairment, including functional and societal limitations and disability,
      with particular emphasis on disability and societal limitations." The current proposal
      directly addresses this recommendation of the NCMRR Advisory Board. It is designed to (1)
      replicate our pilot study with larger sample sizes (2) expand our assessment measures to
      better assess individuals with mild cognitive impairments, thus testing the effectiveness of
      the intervention within this important subpopulation (3) assess the effectiveness of the
      intervention utilizing more global measures of everyday life, including an objective measure
      (the Rivermead Behavioral Memory Test), which has preliminary support through our pilot
      study, as well as additional questionnaires to be completed by both the participant and a
      significant other (4) evaluate the long-term effects of the treatment protocol and (5)
      examine the utility of booster sessions to facilitate long-term treatment effects.

      To meet these study objectives, we will conduct a double-blind, placebo-controlled,
      randomized clinical trial, applying a memory rehabilitation technique to a large sample of MS
      participants. This protocol has been well-validated with other neurological populations and
      preliminary evidence in support of its use in MS now exists. Individuals with MS, with
      documented impairment in memory and new learning, will be randomly assigned to either a
      memory retraining group or a placebo control group. Outcome will be measured through several
      mechanisms: (1) a traditional neuropsychological (NP) battery and (2) an assessment of global
      functioning (AGF) examining the impact of the treatment on daily activities. Both groups will
      undergo baseline, immediate follow-up, and long-term follow-up assessments consisting of a
      traditional NP evaluation, which examines objective performance on well-validated measures of
      cognitive function, and an AGF, which includes self-report measures of memory abilities,
      self-efficacy, quality of life, and occupational functioning. In this way, we will be able to
      objectively evaluate the presence or absence of changes in memory performance through a NP
      assessment, while also evaluating the impact of this treatment protocol on an individual's
      everyday life through the AGF. While most studies evaluating the efficacy of cognitive
      retraining usually employ a pre-training and post-training evaluation, such evaluations have
      been criticized for their lack of ecological validity. The present design allows the
      assessment of the efficacy of this particular memory retraining technique within an MS
      population using traditional measures, as well as the assessment of the impact that such a
      rehabilitation technique has on everyday life. In addition, we will include a 6-month
      follow-up assessment to measure the long-term impact of this treatment on objective cognitive
      functioning, through a NP assessment, and everyday life, through an AGF. Finally, half of the
      participants in the experimental group will participate in monthly "booster sessions"
      following the completion of treatment and we will evaluate the impact of these sessions on
      the maintenance of treatment effects over time. A subset of the sample will also complete pre
      and post neuroimaging to evaluate changes in cerebral activation.

      Many studies have shown that new learning is a key problem in MS. In addition, a small pilot
      study, funded by the National Multiple Sclerosis Society (NMSS) and administered by the
      current PI, tested this memory retraining protocol in an MS population. Results showed that
      when these deficits in new learning are treated, a significant improvement is noted in memory
      performance. However, the impact of the memory retraining protocol on everyday functioning
      remains unclear. The documentation of the efficacy of memory retraining in MS, particularly
      on everyday functioning, could have a significant impact on symptom management and quality of
      life in the lives of persons with MS. As such, specific aims of the current research protocol
      are as follows.

      Aim 1. This study will objectively evaluate the clinical utility of a memory retraining
      protocol to improve performance on objective tests of new learning and memory in a large
      sample of individuals with MS with documented deficits in this area. This protocol has been
      previously utilized in a traumatic brain injury (TBI) population and a small pilot sample of
      individuals with MS, yielding promising data. NCMRR states that research analyzing existing
      rehabilitation techniques, empirically assessing their validity, and providing justification
      to the consumer and practitioners is required for the advancement of the field of medical
      rehabilitation research and recognizes this as a high priority research area. Our study does
      precisely this.

      Aim 2. We will increase the generalizability and real life application of assessment
      techniques by assessing outcome following cognitive retraining with more global measures of
      everyday life. An objective measure of everyday functioning will be included, as well as
      numerous subjective measures of everyday functioning, which will be gathered via established
      self-report instruments, as well as ratings by a significant other.

      Aim 3. This study will also assess the efficacy of this memory retraining protocol in a
      mildly impaired MS group, which has not been properly tested previously. Due to measurement
      ceiling effects in our pilot study, the utility of this technique to improve new learning and
      memory abilities in individuals with mild deficits has not yet been determined. The current
      study improves upon the measurement techniques used in the pilot study.

      Aim 4: This study will evaluate the long-term efficacy of this memory retraining protocol
      through the inclusion of a 6-month follow-up assessment. Many cognitive remediation studies
      in the literature examine the efficacy of the treatment immediately following program
      completion. However, given the time, expense, and labor involved in such intensive treatment,
      it is important to demonstrate the long-term efficacy of such a program. The current study
      therefore goes beyond the typical protocol length to evaluate the long-term impact such
      treatment will have on objective testing and on an individual's daily life.

      Aim 5: Booster sessions have been used to maximize the long term benefit of cognitive
      retraining in other patient populations. However, the utility of booster sessions has never
      been investigated in MS. An additional question we will address in the current treatment
      study is the impact of "booster sessions" following the completion of the treatment protocol.
    

Intervention name(s): memory retraining exercises; placebo control memory exercises
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Memory retraining exercises will be administered on a laptop computer twice a week for five weeks (10 training sessions).; Placebo control memory exercises will be administered on a laptop computer twice a week for five weeks (10 training sessions).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: memory; learning; Multiple Sclerosis; Cognition; treatment; therapy