Cognition-Enhancing Drugs for MS

Medically Reviewed by Christopher Melinosky, MD on April 15, 2022

Multiple sclerosis (MS) may cause cognitive impairment symptoms for many people. You may experience fuzzy thinking or occasional memory lapses, like not being able to come up with a name or the right word in conversation. You may struggle to multitask, make a decision, or focus your attention.

The cause of cognitive impairment in MS is inflammation that damages myelin. This is the protective tissue around your nerve fibers, often in your brain’s white matter. There seems to be a link between lesions on your brain and a decline in your thinking or reasoning skills.

Anywhere from 40% to 70% of people with MS develop some cognitive impairment symptoms.

Is there anything you can do about it? Several medications currently approved for MS may help.

Interferon beta-1a (Avonex, Rebif): Interferon beta-1a is a disease-modifying drug approved to treat MS. It’s made from amino acids, the building blocks of proteins, that are similar to those naturally made in your body. You self-inject this drug into a muscle once a week.

Does it work? Interferon beta-1a can:

  • Slow down the progress of your MS
  • Lower the frequency of MS flares
  • Reduce the number and size of brain lesions seen on your MRI scans

After 2 years on interferon beta-1a, people with relapsing-remitting MS (RRMS) had significant improvement in their learning and memory skills, and they processed information quicker. The drug also improved their problem-solving and ability to judge the size and distance of objects they saw.

What else should I know? Interferon beta-1a’s possible side effects include flu-like symptoms or a skin reaction at the injection site. It may not be right for people with severe depression or suicidal thoughts.

If you become pregnant, your doctor may recommend that you stop using interferon beta-1a until your baby is born. This is out of caution: There’s no evidence that it’s unsafe to use during pregnancy or breastfeeding.

Interferon beta-1b (Betaseron, Extavia): Interferon beta-1b is another disease-modifying drug for MS that’s made from proteins similar to the ones your body makes.

You self-inject this drug under your skin every other day. It comes in prefilled syringes.

Does it work? Interferon beta-1b blocks certain immune cells that cause inflammation and damage in your nerves and brain. In one trial, people with MS who took interferon beta-1b showed improvements in cognitive function over a 5-year period. Results were even better for people who started taking interferon beta-1b early in their disease. They preserved their cognitive skills more than those who started the drug later on.

Another trial included 459 people with early, mild RRMS who took either a 22- or 44-mcg dose of interferon beta-1b for 3 years. They were tested for cognitive function at the start of the trial and then once a year for 3 years. At the end, people who took the higher dose had a 32% lower risk of impairment compared with those on the lower dose.

These results are likely because the drug worked to reduce brain lesions and inflammation. We don’t know for sure if Interferon beta-1b has an effect on cognition, but researchers are studying it.

What else should I know? Interferon beta-1b can cause flu-like symptoms or an injection site skin reaction, but these side effects should lessen over time. If you’re pregnant, have decompensated liver disease, or are sensitive to any ingredients in this drug, you may not want to take it.

Natalizumab (Tysabri): Natalizumab is a biologic drug called a monoclonal antibody. It blocks certain cells from moving into your nerves and brain that cause inflammation during an MS flare. Natalizumab can significantly reduce the number of brain lesions in people with MS. In one study, people who took the drug for 1 year had more than 80% fewer lesions compared with a placebo.

You take natalizumab as an IV infusion once every 28 days. You’ll go to an infusion clinic each month for your 1-hour treatment.

Does it work? In two clinical trials, people with RRMS who took natalizumab showed some improvements in cognitive function on a standard test. In another trial, fewer people with MS had cognitive impairment after 1 to 2 years of treatment with natalizumab compared with the start of the study.

Another study looked at quality of life changes reported by 333 people with MS who took natalizumab. Between 69% and 88% of people said they felt improvements in fatigue and cognition after 12 months.

What else should I know? The most common side effects of natalizumab are:

If you use natalizumab with other immunomodulating drugs, you’re at higher risk of a serious infection called progressive multifocal leukoencephalopathy (PML). Your PML risk goes up after 2 years of infusions.

Fingolimod (Gilenya): Fingolimod is a type of MS drug called a sphingosine 1-phosphate receptor modulator. It works by blocking white blood cells from moving into your nerves, preventing inflammation and nerve damage.

Fingolimod is a pill you take once a day. It can cut your number of MS relapses by as much as 50%.

Does it work? One study from 2017 compared cognitive improvement in 157 people with RRMS who took either fingolimod once a day or interferon beta-1b every other day for 18 months. At the end, everyone in the trial showed improved cognitive function. People who took interferon beta-1b had more and larger brain lesions, and more MS relapses, compared with those who took fingolimod.

What else should I know? Fingolimod’s most common side effects are:

You shouldn’t take fingolimod if you have a suppressed immune system, serious infections like hepatitis or tuberculosis, cancer, or severe liver disease.

Don’t take fingolimod if you’re pregnant, trying to become pregnant, or if you think you might become pregnant. It can cause severe birth defects.

Siponimod (Mayzent): Siponimod is another sphingosine 1-phosphate receptor (S1P) modulator approved for MS. It works on your body’s immune system, keeping white blood cells in your lymph nodes and out of your spinal cord and brain. This drug may prevent inflammation and damage in your central nervous system as well.

Siponimod is a pill you take once a day. Your doctor will test you for a gene called CYP2C9 to find the correct dose for you.

Does it work? Siponimod reduces new brain lesions and keeps existing lesions from growing. This drug significantly improves cognitive function in people with MS, even advanced disease. In a major trial from 2019, siponimod helped people with secondary progressive MS (SPMS) speed up their thinking.

In 2021, 1,651 people with SPMS were randomly prescribed either daily siponimod or a placebo for 12 months. Everyone took three standard cognitive function tests for MS at the start, after 6 months, and at 12 months. After 1 year, the results showed that people who took siponimod were less likely to have sustained loss of cognitive function. They were also more likely to have enhanced cognition than people who took a placebo.

Siponimod improved cognitive function whether or not people had MS relapses before the study, and no matter what level of cognitive function or disability they had at the start. Those with less advanced MS were more likely to show long-lasting improvement with siponimod. People with more advanced disease who took the drug had a lower risk of worsening impairment.

What else should I know? The most common side effects of siponimod are:

  • Headaches
  • Cold/sore throat
  • Urinary tract infections
  • Falls

Less common, but serious, side effects include:

  • Heart rate or heart rhythm changes
  • Macular edema
  • Increased alanine aminotransferase (ALT)

Alemtuzumab (Lemtrada): Alemtuzumab is a monoclonal antibody that blocks a protein on your immune cells called CD52. It’s only approved for people with active relapsing MS after two or more other MS treatments haven’t worked. Alemtuzumab can lower levels of white blood cells that cause inflammation.

You take Alemtuzumab as an infusion in two treatment sessions a year apart. You’ll have an IV drip of alemtuzumab for 5 consecutive days, then 12 months later, follow up with infusions on 3 consecutive days.

Does it work? People in clinical trials who took alemtuzumab had fewer or smaller brain lesions, or no new active lesions.

In a 2018 study, 21 people with active relapsing-remitting MS were treated with both courses of alemtuzumab. They were given thorough cognitive testing both at the beginning of the trial and after the second treatment.

Overall, everyone’s cognitive function either stayed stable or improved with alemtuzumab treatment. Two tests of their thought processing speed significantly improved with alemtuzumab, although their brain imaging scans didn’t show any clear signs of improved disease.

What else should I know? Mild injection site reactions are the most common side effect of alemtuzumab, but these go away quickly. You may have a higher risk of infection after courses of treatment. Rarer, more serious side effects are thyroid, kidney, and blood clotting problems.

Are there any other options? Drugs approved for other brain conditions that cause cognitive decline, like Alzheimer’s disease, are being studied to see if they’re effective for people with MS.

Donepezil (Aricept) is a drug approved to treat mild or moderate dementia in people with Alzheimer’s disease.

In a 2004 study, donepezil improved memory in people with MS who had early cognitive impairment. Unfortunately, a larger trial in 2011 did not show that donepezil improved memory in people with MS compared with a placebo.

Show Sources


Cleveland Clinic: “Multiple Sclerosis (MS): Impaired Cognition,” “Identifying and Managing Cognitive Disorders in Multiple Sclerosis,” “Siponimod,” “Lemtrada (Alemtuzumab),” “Donepezil tablets.”

Multiple Sclerosis Foundation: “Drug Treatment and Cognitive Dysfunction.”

Frontiers in Neurology: “Alemtuzumab Improves Cognitive Processing Speed in Active Multiple Sclerosis: A Longitudinal Observational Study.”

National Multiple Sclerosis Society: “Avonex,” “Betaseron,” “Gilenya,” “Mayzent,” “Lemtrada.”

Multiple Sclerosis and Demyelinating Disorders: “Disease modifying treatments and symptomatic drugs for cognitive impairment in multiple sclerosis: where do we stand?”

MS Trust: “Avonex (interferon beta-1a),” “Gilenya (fingolimod),” “Lemtrada (Alemtuzumab).”

MS Society of Canada: “Avonex,” “Betaseron.”

StatPearls: “Natalizumab.”

Journal of Neurology: “Efficacy of fingolimod and interferon beta-1b on cognitive, MRI, and clinical outcomes in relapsing–remitting multiple sclerosis: an 18-month, open-label, rater-blinded, randomised, multicentre study (the GOLDEN study).”

Medscape: “Siponimod Improves Cognition in Advanced Multiple Sclerosis.”

Neurology: “Siponimod and Cognition in Secondary Progressive Multiple Sclerosis,” “Donepezil improved memory in multiple sclerosis in a randomized clinical trial,” “Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis.”

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