Does simvastatin improve cognitive function in MS?

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.

Chan D, Binks S, Nicholas JM, et al.

Lancet Neurol 2017; 16:591-600.



In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitiveneuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures.


We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin(n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with, number NCT00647348.


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, we 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 Frontal Assessment Battery 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.


To our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on 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.

This reference is included in the neurochecklist:

Multiple sclerosis (MS): emerging treatments

Abstract link


By Solidach – With software of which I am the product manager, CC BY-SA 3.0, Link

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