MS Cognitive Impairment Rates Lower Than Previously Reported

In a large sample of persons with multiple sclerosis (MS), rates of cognitive impairment were unexpectedly low and few had severe impairment, according to findings of a cross-sectional study reported online August 1 in PLOS ONE (Achiron et al., 2013).

“Cognitive decline may appear early in the [MS] disease process and has been reported even at disease onset,” wrote Anat Achiron, M.D., Ph.D., from the Multiple Sclerosis Center of Sheba Medical Center in Tel-Hashomer, Israel, and colleagues. “Prevalence of cognitive impairment in MS has been estimated [at] 20% to 65% of patients. This wide range is probably related to variation in the disease subtypes, disease duration and level of disability of the MS population studied, as well as to differences in the cognitive assessment scales, procedures and tools used.”

Due to the absence of large-scale population studies measuring rates and dynamics of cognitive decline in MS, the investigators studied patterns of cognitive impairment in 1,500 persons with MS and disease duration of up to 30 to 55 years.

They used a computerized cognitive battery that assessed verbal and nonverbal memory, executive function, visual-spatial perception, verbal function, attention, information-processing speed, and motor skills. The investigators defined cognitive impairment as scores lower than one standard deviation (SD) from healthy population norms matched for age and educational level, and they defined severe cognitive impairment as scores 2 SDs lower.

Cognitive Impairment Worse in SPMS

Compared with healthy population norms, this MS sample had poorer cognitive performance, particularly in information-processing speed and executive function. Except in the visual-spatial domain, cognitive performance was worse in persons with secondary progressive MS (SPMS) than in those with clinically isolated syndrome, relapsing-remitting MS (RRMS), or primary progressive MS (PPMS). However, mean disease duration was twice as long in SPMS as in RRMS or PPMS.

The level of cognitive impairment reached statistical significance only in persons with a disease duration exceeding 5 years. One in five persons with MS (20.9%) had cognitive impairment by the fifth year from disease onset (p = 0.005), and 6.0% had severe cognitive impairment (p = 0.002). By 10 years from onset, these proportions were 29.3% and 9.0%, respectively (p = 0.0001). Cognitive impairment may precede MS onset by 1.2 years, based on regression modeling.

The most significant contributor to variation in cognitive performance was neurological disability, implying that persons with active MS who become more disabled faster are also more vulnerable to early cognitive decline.

“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,” the study authors wrote. “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.”

Key open questions

• Do different MS subtypes vary in their predisposition to cognitive impairment due to differences in the underlying pathophysiology, or is the observed difference solely due to disease duration and accumulated disability?
• Which therapeutic interventions would be most effective early in the course of MS to delay or prevent cognitive impairment?

Disclosures

A Sheba Medical Center research grant for excellency in medicine funded this study. NeuroTrax Corporation and MediStat Ltd. employ two of the study authors. The Sheba Medical Center and NeuroTrax Corp. had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.