Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study

Abstract

Background/aims: Large-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS) are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years.

Methods: 1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD) and severe cognitive impairment as below 2SD for age and education matched healthy population norms.

Results: Cognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p=0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p=0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p=0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years.

Conclusions: The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.

Figure 1. PCA of cognitive performance in MS.

PCA of cognitive performance in CIS patients (N = 187, blue dots), RRMS patients (N = 1173, green dots), SPMS patients (N = 100, purple dots) and PPMS patients (N = 27, red dots) demonstrates that cognitive performance in the different disease types are clustered together with a probability of 76.8%. Each dot represents how the sample (subject) is localized in space on the basis of its cognitive performance. The distance between any pair of points is related to the similarity between the two observations in high-dimensional (3D) space.

Figure 2. Cognitive performance as a function of MS disease duration.

Cognitive performance for MS patients with disease durations of 1 to 30 years (5-year intervals) with 95% confidence intervals for GCS (A) and individual cognitive domains (B–H), N = 1500.

Figure 3. Percent of MS patients with cognitive impairment by disease duration.

The percent of patients with impairment in GCS at a cutoff of 85 (1SD below the normalized mean, white bars) and at a cutoff of 70 (2SD below the normalized mean, black bars) is presented by disease duration. The dashed bars represent the percent of patients with GCS ≥85. N = number of patients; *p≤0.005; **p<0.001; ***p<0.05.

Figure 4. Cognitive performance by GCS within the first year from MS onset, N = 187.