Physicians around the country are launching the first large-scale clinical study ever to address the same kinds of cognitive symptoms in patients with multiple sclerosis as those that may affect President Jeb Bartlet (played by Martin Sheen) on future episodes of the TV show West Wing. The work builds on a smaller study by doctors at the University of Rochester Medical Center in which several patients with MS improved while on a medicine currently used to treat memory problems in patients with Alzheimer's disease.
While symptoms like muscle weakness and fatigue are widely recognized as part of MS, the cognitive problems that affect up to 60 percent of patients are not. But having trouble remembering events or conversations, an inability to concentrate, or difficulty finding words, all due to the subtle damage MS causes in the brain, are a big part of the disease for many patients.
"When MS was first described more than 100 years ago, there was a lot of discussion about cognitive impairment. Somehow doctors lost touch with that aspect of the disease until recent years, when we're recognizing again that it's a significant problem," says Steven Schwid, M.D., assistant professor of neurology, who is lead investigator for the new study.
The study will include 240 patients at 21 hospitals and medical centers around the country. The drug under study is currently approved only for the treatment of mild to moderate dementia from Alzheimer's disease.
About 350,000 people in the United States have multiple sclerosis, which almost always strikes in young adulthood; besides trauma, it's the top cause of disability in young adults. MS is an autoimmune disease in which the body attacks its own tissues, damaging nerve pathways in the brain and spinal cord.
Symptoms vary greatly, depending on what nerves are damaged, but generally include muscle weakness, cognitive problems, problems with touch and vision, and difficulty with bladder control. Early in the course of MS, symptoms can go into remission for years, then suddenly cause sudden and severe attacks; in others, symptoms worsen gradually over the years. Cognitive problems are unpredictable: Some patients never have a problem, while others have tremendous difficulties with memory, attention, and concentration soon after being diagnosed.
"In the last few years several medicines have become available to treat MS," Schwid says. "These medications help slow the progression of the disease, holding symptoms more stable, but they do not improve symptoms that are already present. Right now there is nothing to treat the difficulties with memory that many patients experience."
Last year Pierre Tariot, M.D., professor of psychiatry, medicine, and neurology at the University, reported the results of a preliminary study of 17 patients who had advanced MS and severe cognitive impairment. During the three months they were on the medicine, patients' concentration, memory, and attention span improved on average; many were also better able to hold a conversation, learn new information, and were more interested in people and activities. A battery of sophisticated cognitive tests indicated that in some cases the patients with MS improved more than patients with Alzheimer's typically have improved in similar studies.
The results were published in the Journal of Clinical Psychopharmacology. Besides Tariot and Schwid, other authors included Yvonne Greene, M.D.; Heather Wishart, Ph.D.; statistician Christopher Cox, Ph.D.; analyst Connie Holt; and John Noviasky.
"Half the patients showed clearly observable improvement - you could tell simply by chatting with them that they were thinking more clearly. In many patients we also saw changes in temperament; they were often less irritable, depressed, or agitated," says Tariot, who helped design the current multicenter study. While the results appeared dramatic, the previous study had limitations, including a small sample size and lack of a control group. That's why researchers decided to conduct the current study.
The work had its genesis in a question an MS patient put to Tariot about four years ago. The patient noticed that his memory wasn't as good as it had been and felt that his cognitive abilities generally were slipping. He asked Tariot if a medication used for similar symptoms in Alzheimer's disease might help. "We acquiesced to his wishes, and the improvement in his abilities to concentrate and remember things was so dramatic that it convinced us to take a more systematic look."
The medicine works by boosting the amount of acetylcholine, a chemical crucial to memory, available in the brain. The same chemical plays a role in many conditions, including bipolar disorder, head injury, schizophrenia, Parkinson's disease, and HIV-related dementia.
"Since the medicine is useful for one disease where there are cognitive problems, Alzheimer's, we think it may be useful for others," says Tariot. "These drugs don't 'know' they're supposed to work only in Alzheimer's disease. It makes great sense to ask whether folks who have cognitive problems caused by other diseases can be helped with these medicines."
List of participating sites:
Albany, NY: Neurological Associates of Albany
Albuquerque, N.M.: University of New Mexico School of Medicine
Baltimore, Md.: University of Maryland Hospital
Birmingham, Ala.: University of Alabama
Brooklyn, N.Y.: Malmonides Medical Center
Buffalo, N.Y.: Millard Fillmore Hospital
Chicago, Ill.: University of Chicago
Columbus, Ohio: Ohio State University
Denver, Colo.: University of Colorado Health Sciences Center
Detroit, Mich.: Wayne State University School of Medicine
Indianapolis, Ind.: Indiana University
Los Angeles, Calif.: University of California at Los Angeles
Loma Linda, Calif.: Loma Linda University
Minneapolis, Minn.: Noran Neurological Clinic
New York, N.Y.: Mount Sinai School of Medicine
Philadelphia, Pa.: University of Pennsylvania
Portland, Ore.: Oregon Health Sciences University
Rochester, Minn.: Mayo Clinic
Rochester, N.Y.: University of Rochester Medical Center
Seattle, Wash.: University of Washington
Winston-Salem, N.C.: Wake Forest University School of Medicine