Can we predict cognitive decline after initial diagnosis of multiple sclerosis? Results from the German National early MS cohort (KKNMS)

Abstract

Background Cognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis. Methods Neuropsychological screening data from baseline and 1-year follow-up of a prospective multicenter cohort study (NationMS) involving 1123 patients with newly diagnosed MS or CIS were analyzed. Employing linear multilevel models, we investigated whether demographic, clinical and conventional MRI markers at baseline were predictive for CI and longitudinal cognitive changes. Results At baseline, 22% of patients had CI (impairment in ≥2 cognitive domains) with highest frequencies and severity in processing speed and executive functions. Demographics (fewer years of academic education, higher age, male sex), clinical (EDSS, depressive symptoms) but no conventional MRI characteristics were linked to baseline CI. At follow-up, only 14% of patients showed CI suggesting effects of retesting. Neither baseline characteristics nor initiation of treatment between baseline and follow-up was able to predict cognitive changes within the follow-up period of 1 year. Conclusions Identification of risk factors for short-term cognitive change in newly diagnosed MS or CIS is insufficient using only demographic, clinical and conventional MRI data. Change-sensitive, re-test reliable cognitive tests and more sophisticated predictors need to be employed in future clinical trials and cohort studies of early-stage MS to improve prediction. Electronic supplementary material The online version of this article (10.1007/s00415-018-9142-y) contains supplementary material, which is available to authorized users.

Longitudinal patterns of cortical thinning in multiple sclerosis

“…However, a paradoxic significant improvement of those scores was evident in our patients in both scores, which may be attributed to a learning effect through repetition. This is in line with a number of studies including healthy controls and MS patients showing improved cognitive performance through practice or repetitive testing, even when testing was performed with relatively long intervals between follow‐up, similarly to our study (Baird, Tombaugh, & Francis, ; Bartels, Wegrzyn, Wiedl, Ackermann, & Ehrenreich, ; Basso, Bornstein, & Lang, ; Johnen et al, ; Roar, Illes, & Sejbaek, ).…”

Longitudinal Serum Neurofilament Levels of Multiple Sclerosis Patients Before and After Treatment with First-Line Immunomodulatory Therapies

“…We did not observe a positive correlation between serum NfL and EDSS for all time points, which is not surprising as this was also not seen in other studies [31] or only described in larger cohorts and with patients more severely affected by the disease and accordingly with higher EDSS [22,32]. The same was true for the correlation of serum NfL and PASAT as cognitive functions are only mildly affected in the early phase of the disease [33]. Even though, in a previous study, we observed an association of a more active disease course with higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines in a subpopulation of our study cohort [29], there was no correlation of serum NfL with any of the observed cytokines in the present study.…”

Is APOE ε4 associated with cognitive performance in early MS?

“…Patients with a higher disability level as assessed by the EDSS and with a higher number of T2 lesions in MRI performed worse in cognitive testing, which is in line with previous reports. 17,23,32 Higher scores of depressive symptoms in BDI-II were also associated with an impaired performance. Depression is known to be associated with reduced attention and processing speed in patients with MS. 33 As PASAT 3 and MUSIC tests both include an assessment of these cognitive domains, our current finding seems plausible.…”

“…16 Individual PASAT 3 test scores were z-standardized, stratified for age and education based on normative data from a German sample of n = 241 healthy controls. 17,18 MUSIC is a brief multiple-domain cognitive screening test, which is widely used in German-speaking countries and was developed for the rapid assessment of the most frequently impaired cognitive domains in patients with MS. It consists of 5 cognitive subtests.…”

“…19 Individual test scores were z-standardized based on normative data from n = 158 German-speaking healthy young adults. 17,19 All tests were taken for the first time at study enrollment so that results were not expected to be biased by learning effects.…”