Cognitive performance profile in different phenotypes of MS with cognitive complaints
Introduction
Multiple sclerosis (MS), the most common disabling neurological disease in young and middle-aged adults, is characterized by a variable disease course. In most of the patients (80%) the disease emerges with relapsing remitting (RRMS) course characterized by episodes of acute exacerbation followed by almost complete recovery. Approximately 50–60% of RRMS patients progress to secondary progressive (SPMS) disease characterized by disease progression with or without relapses, remissions, and plateaus. About 15% of patients evidence a primary progressive (PPMS) disease course from onset characterized by continuous deterioration without distinct relapses (Antel et al., 2012). The conversion from RRMS to progressive course tends to occur between 35 and 50 years of age, which is the same as the typical age of disease onset in patients with PPMS. Magnetic resonance imaging (MRI) findings, cerebrospinal fluid banding, evoked potentials, genetics, or neuropathology are not objectively distinguishable between primary progressive and relapsing forms of the disease (Rice et al., 2013). Recent findings suggest that MS might be a single disease entity with several distinct clinical phenotypes (Lassmann et al., 2012, Rice et al., 2013).
Cognitive impairment is present in 50–60% of patients with MS, encompassing all disease stages and types of clinical course (Langdon, 2011). The cognitive functions most often affected are information processing speed, memory, executive functions and complex attention (Chiaravalloti and DeLuca, 2008, Langdon, 2011). Most of the evidence at present suggests that cognitive deficits are more frequent and more widespread in progressive than in relapsing form of the disease (Gaudino et al., 2001, Huijbregts et al., 2004, Lynch et al., 2005, Potagas et al., 2008, Rodrigues et al., 2011, Ruet et al., 2013, Sepulcre et al., 2006). However, the findings are not consistent. It has also been concluded that cognitive impairments may be infrequent in PPMS (Comi et al., 1995, Thompson et al., 1997). Similarly, patients with SPMS have been found to have more frequent and more severe cognitive impairment (Comi et al., 1995, Denney et al., 2005, Huijbregts et al., 2004, Potagas et al., 2008) than patients with PPMS. In contrast to these, also similar cognitive performance in the two types of progressive disease courses has been reported (Foong et al., 2000).
Cognitive impairment has mostly been found to be unrelated to physical disability and disease duration in MS (see reviews Chiaravalloti and DeLuca, 2008, Langdon, 2011). At the same time, a significant relationship between physical disability and cognition in studies representing larger samples has been reported (Lynch et al., 2005). Longitudinal studies of short timeline (1 to 4 years) have failed to show significant cognitive decline, but in longer follow-up (10 or more years) cognitive impairment seems to progress (Langdon, 2011).
The relationship between cognitive impairment and disease course and severity of MS is not well understood. Against this background, the aim of the present study was to evaluate whether patients with different clinical phenotypes (RRMS, SPMS, PPMS) or different stages of disability (EDSS 0–4.0, EDSS 4.5–6.0, EDSS>6.0) and with cognitive complaints show a different cognitive impairment profile in the brief repeatable battery of neuropsychological tests (BRBNT).
Section snippets
Participants
The study population consisted of a pooled sample of MS patients also included in two previous study samples. Both studies included patients participating in outpatient rehabilitation. In the first study (n=98), patients with moderate to severe MS (EDSS 4.0–8.0) with subjective cognitive complaints (patient report) and willingness to participate in outpatient rehabilitation were included. In the second study (n=98), patients with mild to moderate MS (EDSS 0–5.5) with subjective cognitive
Clinical phenotypes (RRMS vs. progressive)
RRMS patients were younger than patients with progressive disease course. Neither education in years nor gender distribution differed between the groups. RRMS patients had lower EDSS scores than patients with progressive disease course. Disease duration was longer in patients with progressive course, compared to RRMS patients. Mood or perceived psychological burden of the disease did not differ between the groups. Patients with progressive disease course reported more physical burden of the
Discussion
To our knowledge, this is the first study to compare the cognitive performance profile of MS patients with subjective cognitive complaints in different disease types and severity. The association between cognitive dysfunction and severity of disability or disease duration was weak. Slight differences were found among the disease phenotypes. RRMS patients performed better than the patients with progressive disease (SPMS, PPMS) course in one cognitive test, the SDMT. When RRMS, SPMS and PPMS
Conflict of interest statement
None related to this specific study. The study was funded by the Finnish MS Foundation.
Acknowledgments
We thank all our patients for their time and interest in this study. The study was funded by the Finnish MS Foundation, which is gratefully acknowledged.
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