While many symptoms of MS throughout the body can be caused by lesions in either the brain or the spinal cord, cognitive symptoms of MS — those related to your memory, language, and problem solving — are believed to be caused only by lesions in the brain. Brain lesions are a hallmark of MS, but they’re not the only way MS can affect your brain function. MS can also contribute to brain atrophy, or shrinkage, over time — a process that occurs in all people as they age, but typically happens much more quickly in people with MS. Brain atrophy, in particular, can contribute to cognitive symptoms of MS. According to Dr. Cross, this process involves immune system cells and other substances entering the brain and not just acting on their own, but also “recruiting” local cells to secrete pro-inflammatory substances in the area. Some of these cells and substances attack myelin, a white fatty substance that covers nerve fibers in the brain and elsewhere. A nerve fiber (also known as an axon) is a long, narrow part of a nerve cell (neuron) that extends from the main body of the cell. It transmits signals from the nerve cell to other cells and tissues. Depending on the specific cell or tissue it connects to, a nerve cell can play a role in any number of the body’s normal functions, from thinking and talking to walking and moving your arms. Myelin acts as a protective layer on the outside of nerve fibers. When this layer is damaged, nerve fibers can become exposed, which may cause them to transmit signals erratically or less efficiently. “If you have an active MS lesion, under the microscope it would have lots of inflammatory cells there, and it would have greatly reduced myelin, but the nerve fibers would mostly still be there,” says Cross. Even without medical treatment, brain lesions in MS don’t simply keep growing and growing. “The body calms down these lesions and surrounds them, and they stop,” says Cross. If a lesion forms but doesn’t develop past a certain point, it may cause few or even no symptoms. “You might see a region that’s demyelinated, but the nerve fibers are still there and haven’t been damaged too much,” Cross explains. “And that person may have no functional deficits from that lesion.” But in some lesions, the nerve fibers themselves become heavily damaged and die off as a result. That stops the affected nerve cells from sending signals and can result in a permanent loss of cognitive or physical function. It’s normal to lose 0.1 to 0.5 percent of brain volume each year as you age. However, in people with MS, this range is typically 0.5 to 1.35 percent, according to an article published in September 2016 in the journal Multiple Sclerosis and Related Disorders. This greater atrophy may begin even before an MS diagnosis. When nerve fibers die off in significant numbers due to an MS lesion, myelin is lost from the areas of the brain outside that lesion. That’s because nerve fibers can be very long, extending from one area of the brain to another. A lesion may affect only a small portion of a nerve fiber at first, but when the nerve fiber dies, myelin is lost from the entire length of that fiber beyond the lesion. Neurologists commonly think about the brain as a mix of gray matter and white matter. Gray matter consists of the main bodies of nerve cells, while white matter consists of the nerve fibers that extend from these bodies. White matter gets its color from the myelin that surrounds nerve fibers. So when myelin is lost in areas outside lesions, it tends to cause atrophy of white matter. But brain atrophy due to MS isn’t limited to white matter. Loss of nerve fibers can lead to the death of entire nerve cells, which means loss of the main nerve cell bodies that make up gray matter. This gray matter atrophy “is more associated with functional consequences than white matter atrophy” is, says Cross. Scientists are still trying to figure out which symptoms are likely to be caused by atrophy of particular areas of the brain. “The human brain is so interconnected that it’s difficult to say, ‘This dysfunction is due to that region,’” Cross explains. “Memory and cognition are particularly difficult to pin down to any particular region.” Cognitive symptoms in MS are often related to memory, says Cross — but not forgetting skills or information in the way that someone with dementia would. Instead, “many people with MS have trouble with multitasking, keeping two or three things going in their mind at the same time,” she explains. The National MS Society published cognitive screening recommendations for people with MS in October 2018 in the Multiple Sclerosis Journal. These recommendations include getting a baseline cognitive screening as early as possible when your condition is clinically stable and then following up with the same mode of screening every year. Screening may also be repeated more often than once a year to assess the effects of a new or changed treatment, to evaluate progression of cognitive impairment, or to screen for new cognitive problems. People who have MS may also experience reduced visual or verbal memory. “One of the tests I like to use is to take the word ‘world’ and ask patients to put the letters in alphabetical order, without using a piece of paper,” says Cross. Many people who have MS describe their experience of cognitive problems as a kind of “fog” (cognitive fog, or “cog fog”) that makes it difficult to form certain thoughts or complete mental tasks. In particular, that means taking steps to limit your risk of developing cardiovascular disease. Poor blood flow to your brain could have an impact on your ability to think, and small strokes that you might not even notice could be “critically bad” for cognitive health in someone with MS, according to Cross. One reason it’s important to keep your brain as healthy as possible when you have MS is that other areas of the brain can take over for damaged areas to some degree — a concept known as cognitive reserve (or neurological reserve). This may explain why some people develop lesions and atrophy that don’t seem to cause symptoms. While all the factors behind cognitive reserve aren’t understood, your overall brain health may play a role. The good news is that there are many steps you can take to help preserve your mental abilities when you have MS.
