COGNITION IN PROGRESSIVE MS (The simvastatin Study)

Cognitive impairment in multiple sclerosis can occur from the earliest stages of the disease and its prevalence can exceed 80% in some studies of secondary progressive multiple sclerosis (SPMS). The cognitive domains most frequently affected in multiple sclerosis are speed of information processing, attention, episodic memory, and executive function.

The effect of cognitive impairment in multiple sclerosis on daily function can be substantial, and greater than the effect of physical disability on quality-of-life measures such as independence, social inclusion, and mood. In view of this effect, a 2013 international position paper highlighted development of effective interventions to treat cognitive impairment as a key goal in multiple sclerosis.

In a large study of patients with primary progressive multiple sclerosis (PPMS), baseline impairments of verbal memory, attention, verbal fluency, and spatial reasoning were identified, with cognitive decline occurring in a third of patients after 2 years.

Statins in SPMS

• Statins are widely used for the treatment of vascular diseases, and have an excellent safety profile and low cost.
• In addition to their beneficial effect on hypercholesterolaemia, statins exert immunomodulatory and neurotrophic effects.

Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Dennis Chan, Sophie Binks, Jennifer M Nicholas, Chris Frost, M Jorge Cardoso, Sebastien Ourselin, David Wilkie, Richard Nicholas, Jeremy Chataway. The Lancet Neurology, Aug 2017: Volume16, Number8; p591-600

Study aims: MS-STAT cognitive substudy, in which the researchers investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures.

Results:

• Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB).
• Over the entire trial, they noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001).
• At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes.

Discussions:

• To the researches’ knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments.
• They found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure.
• Although they found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials.

Simvastatin Prospective Study

• This phase 3 trial will involve over 1180 people with secondary progressive MS. It begins in summer 2017 and will take six years to conclude in 2023.
• It is a multi-centre UK (may be enter-European as well) study.
• It will be open to every one in the UK with SPMS who fulfils the study criteria.
• If successful, simvastatin could be among the first treatments licensed for secondary progressive MS.