Cognitive impairment in Multiple Sclerosis: Investigating the temporal dynamics of functional reorganization, cognition, and the susceptibility to change after cognitive rehabilitation

Cognitive impairment is a frequent and highly disabling complaint in multiple
sclerosis (MS). Important new insights into the pathophysiology of MS cognitive
impairment have been gained, which are consistent with a *functional
reorganization model*. This model implies that cognitive impairment is preceded
by reorganization of brain function (as measured with functional magnetic
resonance imaging (MRI)) and is regarded as a crucial compensatory mechanism
that counterbalances on-going brain damage and delays the onset of MS cognitive
decline. However, longitudinal studies are crucially lacking and required to
understand the temporal dynamics of this compensatory mechanism. Recently,
it-has been shown that functional reorganization can be enhanced via cognitive
intervention, which might have beneficial effects on patients* cognitive
functioning.

The aim of the proposed study is to obtain insight into the temporal dynamics
of functional reorganization and cognition, and to assess the effect of
cognitive rehabilitation on this adaptive mechanism and cognitive functioning.

The proposed study is a 5-year follow-up of a well-defined cohort of 85
subjects (35 cognitively preserved (CP) and 20 cognitively impaired (CI) MS
patients, 30 healthy controls). In the initial study, subjects received
detailed neuropsychological testing and structural and functional MRI, which
will be repeated for the follow-up study. Subsequently, a well-established
cognitive rehabilitation program focusing on attention will be offered to the
MS patients. Its effect on cognitive improvement and/or changes in functional
reorganization will be assessed directly after intervention (short-term) and 3
months after intervention (long-term).

A computer-based attention training will be provided for 7 weeks (once a week,
45 minutes per session) in the experimental group. The control group (waiting
list) will not engage in any cognitive rehabilitation program

All subjects will visit our outpatient clinic to undergo neuropsychological
testing (approximately 60 minutes) and MRI scanning (approximately 70 minutes).
Patients are asked to participate in the cognitive rehabilitation program, for
which they have to visit the outpatient clinic directly after intervention
(same measures as first visit) and 3 months post intervention (only
neuropsychological testing). Prior to each measurement, subjects have to fill
in several questionnaires at home (approximately 30 minutes). Additionally,
patients will undergo EDSS examination by telephone. The congitive
rehabilitation program will last for 7 weeks, and patients have to train once a
week for 45 minutes. Therefore, the burden for patients is relatively low.

There are no risks associated with participation, becasue MRI is a safe
technique (subjects will be screened for exclusion criteria and earplugs will
be provided to reduce scanner noise) and no adverse effects are expected
related to the cognitive rehabilitation program.