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Title: Burden of Disease Predicts Cognitive Status at 16 Years: Presented at ECTRIMS
URL: http://www.pslgroup.com/dg/2161C2.htm
Doctor's Guide
October 22, 2007


By Chris Berrie

PRAGUE, CZECH REPUBLIC -- October 22, 2007 -- Disease activity and progression in the early stages of disease determine the cognitive status 16 years later in patients with multiple sclerosis (MS), according to results of a multicenter, long-term follow-up, observational study presented here at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

On October 14, Dawn W. Langdon, PhD, Neuropsychology Lead and Reader in Neuropsychology, Royal Holloway, University of London, London, United Kingdom, presented this collected cross-sectional data from patients with MS who participated in a pivotal North American Interferon Beta-1b trial on behalf of the 16-Year Long-Term Follow-Up Study Group.

"Cognition is a very important aspect for people with MS… and its negative impact is over and above that caused by the physical disability," Dr. Langdon said.

Thus, the cognitive deterioration that occurs over time during the progression of MS affects many aspects of life, although cognition is not usually tested in detail at the bedside or in clinical trials. Indeed, cognition in the later stages of MS has received very little attention, where the physical impairment of the patient overshadows the intellectual decline.

Moderate correlations have been demonstrated between progression of cognitive impairment, increasing lesion load, and atrophy in patients with MS. However, the relation of physical disability and magnetic resonance imaging (MRI) measures to cognition in MS has appeared to be relatively weak.

Dr. Langdon and colleagues thus used the unique dataset from the original North American trial on interferon beta-1b to determine whether the patient characteristics at trial entry can predict later cognitive outcome. This was achieved by the application of five tests of current cognitive function, with the individual z scores being summed together to produce a cognitive performance index (CPI) score. The tests used were: the Wechsler Test of Adult Reading Ability (WTAR); the Controlled Oral Word Association Test (COWAT); the California Verbal Learning Test-II (CVLT-II); the Paced Auditory Serial Addition Task-3 (PASAT-3) Symbol Digit Modalities Test (SDMT, oral version); and the Delis-Kaplan Executive Function System (D-KEFS).

The 16-Year Long-Term Follow-Up Study Group included 179 of the original 372 patients who participated in this trial. The group had a mean age of 51.4 years, was 67% female, and had a mean estimated premorbid intelligence quotient of 102.9, which was classified as average.

The median score on the baseline Expanded Disability Status Scale (EDSS) was 2.5 and the median baseline MRI T2 burden of disease (BOD) was 1,235.56 mm2. At the 16-year follow-up, the values were EDSS 4.5 and MRI BOD 11,091.40 mm2. Patients also had current T1 black holes of 4380.15 mm2 and a normalized brain volume of 73.5%.

Dr. Langdon noted that the MRI data taken 16 years after the start of the study are not directly comparable with the baseline data because of differences in scanners, scanning sequences, and parameters.

The mean raw scores on the cognitive tests were what might be expected for MS patients with advanced disease, Dr. Langdon indicated, and their high degree of partial correlation demonstrated the reliability and coherence of these cognitive data.

Calculations of the Pearson partial correlation coefficients of the cognitive raw scores and the CPI scores with current EDSS scores and the full MRI data demonstrated significant correlations across all of the relationships (P <.01 to P <.001). Furthermore, when also applied to the baseline EDSS and T2 BOD, the relation to the cognitive raw scores and the CPI were again found to be significant (P <.05 to P <.001), indicating that baseline EDSS and MRI can predict cognition 16 years later.

Application of the multiple linear regression model to the dataset demonstrated that the independent predictors of CPI were: premorbid IQ (P <.0001); EDSS at baseline (P =.0001); MRI T2 BOD at baseline (P <.0001); and MRI T2 activity at 2 years (P =.0098).

Change in EDSS from baseline to last visit after 2 years almost reached significance as an independent predictive variable (P =.0526).

Dr. Langdon stressed, "Together, these predictors accounted for 44% of the variance in the cognitive function 16 years later."

Therefore, apart from the patient premorbid intellectual level, it was the neurological measures of disease severity in the early years of this trial that were the only other significant predictors of cognitive outcome 16 years later.

Funding for this study was provided by Bayer Schering.


[Presentation title: EDSS and MRI Burden of Disease Predict Cognitive Status at 16 Years: Data From the Long-Term Follow-up Study. Abstract 116]

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