Memory problems can be a significant and often under-appreciated consequence of the brain dysfunction associated with multiple sclerosis (MS). Over the past 15 years, my work has been geared toward understanding the nature of these memory impairments, identifying the variables which compound the problem, examining how impaired memory affects everyday life and learning about the cerebral changes underlying such cognitive problems and what treatments are effective in improving memory performance and quality of life.
It was just 35 years ago that physicians and scientists believed that cognitive impairment was only observed in about 3% of persons with MS. Patients were told that their cognitive complaints did not exist or were a consequence of depression or anxiety. Today, after two decades of neuropsychological research, we know that cognitive impairments are real and are observed in up to two-thirds of persons with MS. Problems in learning and memory are by far the majority of patient complaints and the area which has received the most research attention. My work started with a grant from the Foundation of UMDNJ about 15 years ago, challenging the then accepted notion that memory impairment in MS was due to difficulties in the retrieval of the memory trace from long-term storage. In a series of studies, we were able to show that this conclusion was incorrect due to confounds and flaws in experimental design. Our work showed that, in fact, persons with MS were impaired in the initial acquisition of information from the environment (i.e., impaired learning) and that if learning was equated with healthy controls, MS subjects showed perfectly normal recall and recognition (i.e., intact retrieval), even up to one week after learning. That is, the problem persons with MS face is in the quality of learning and encoding information, and retrieval from storage in the brain is in fact “normal” (i.e., normal forgetting).
With grants from the National Multiple Sclerosis Society and an RO1 from the NIH, we subsequently conducted a series of studies identifying which variables lead to diminished learning in MS. We found that factors such as slowed information processing speed, susceptibility to interference, and compromised executive functions (e.g., impaired planning and organization) all contribute to decreased learning efficiency. This work led us to the model that certain cognitive factors (such as slowed processing speed or impaired organization and planning) decreased the quality and efficiency of learning from the environment. That is, when persons with MS were required to recall information, they would only be able to recall this less than accurate store of information from long-term storage. With additional funding from the National Multiple Sclerosis Society, we set out to examine how impaired learning and memory affect everyday life activities. Most studies to date on the impact of MS on everyday life rely almost exclusively on self and/or family reports of functional activity. We asked MS patients and their families to subjectively report how cognitive impairment affects everyday functional activities and compared this with an objective and quantitative assessment of actual everyday activities such as meal preparation, paying bills and following a regimen of taking medicines. Our results showed that neuropsychological impairment predicted actual performance of everyday life activity. However, patient self-report was associated with emotional distress (e.g., depression and anxiety) and not the actual performance of everyday life activities. These results showed that neuropsychological factors are clearly related to the ability to perform everyday life activities which are cognitively demanding (e.g., driving an automobile). In addition, patient self report provides information on how the patient “feels” about his/her disability.
Now that we understood the nature of memory impairment in MS and the factors related to impaired learning and its effects on everyday life, the next step in our work was to decide what can be done to improve this cognitive impairment. Thus our research now focuses on cognitive rehabilitation. We are studying techniques from cognitive psychology known to improve learning efficiency in laboratory studies of healthy subjects to see if these can be applied to persons with MS. My colleague Nancy Chiaravalloti, PhD, and I led a pilot clinical trial, funded by the National Multiple Sclerosis Society, to examine if behavioral techniques can be used to improve learning efficiency in MS. Patients with MS were taught to use context and imagery to improve the quality of encoding new information. The initial data was extremely positive and today Dr. Chiaravalloti is the recipient of an RO1 from the NIH to conduct a full-scale, doubleblind, placebo-controlled clinical trial to improve learning and memory in persons with MS.
Dr. Chiaravalloti and our team have also been involved in several other studies using behavioral techniques to improve learning efficiency in persons with MS. For example, Yael Goverover, PhD, formerly a post-doctoral fellow in our laboratory and now an assistant professor at NYU, received a grant from the National Multiple Sclerosis Society to examine how specific behavioral techniques (e.g., self-generation and spaced learning) can improve everyday life activities. An occupational therapist by training, Dr. Goverover has designed a series of cognitive rehabilitation studies to improve the quality of encoding during learning and see if this can advance actual everyday functional tasks. While these studies are currently underway, the preliminary results are very encouraging. In addition to using behavioral interventions, Dr. Chiaravalloti and I received funding from the National Multiple Sclerosis Society to conduct a pilot study examining if a new medication (Modafinil) can improve learning and memory in persons with MS.
The final branch of our 15-year line of research in MS was to examine how cognitive changes are manifested in the brain. Thus, we have conducted a series of studies using functional neuroimaging (e.g., fMRI) to examine how pathways in the brain are altered when persons with MS have cognitive problems (see article on page 15).
Overall, our goal is to enhance the quality of life of persons with MS by improving our understanding of the specific nature of cognitive impairment and its mechanism of action in the brain, and by studying rehabilitation techniques which can impact everyday life. We have indeed progressed significantly from where we were 35 years ago, but realize that as long as persons with MS are disabled, we have additional work ahead of us.
John DeLuca, PhD, is a professor in the Department of Physical Medicine and Rehabilitation at UMDNJ-New Jersey Medical School, and the director of the Neuropsychology and Neuroscience Laboratory at KMRREC. He obtained his BA in psychology from William Paterson University and his MA and PhD from SUNY-Binghamton in behavioral neuroscience, and completed a fellowship in clinical neuropsychology from the JFK Johnson Rehabilitation Institute. Dr. DeLuca has received grants from the National Institutes of Health, the National Institute on Disability and Rehabilitation Research, the National Science Foundation and the National Multiple Sclerosis Society, among others. He serves on the editorial board of several journals and is the associate editor of the Archives of Physical Medicine and Rehabilitation. He is also the editor of the book “Fatigue as a Window to the Brain.”