Improving New Learning and Memory in Multiple Sclerosis

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.