In patients with multiple sclerosis, cognitive reserve is associated with greater cerebral efficiency and appears to protect against cognitive decline.
SAN ANTONIO—A life filled with intellectual enrichment can help to shield patients with multiple sclerosis (MS) from cognitive impairment, according to research presented at the 24th Annual Meeting of the Consortium of Multiple Sclerosis Centers.
“Environmental enrichment can protect against disease severity,” said John DeLuca, PhD, Professor of Physical Medicine and Rehabilitation, University of Medicine and Dentistry of New Jersey–New Jersey Medical School, in Newark. “We think this is very critical and very important in even thinking about MS rehabilitation.”
The Cognitive Reserve Hypothesis
Dr. DeLuca and colleagues conducted four studies (all led by James F. Sumowski, PhD) on cognitive function in MS. Although 50% to 70% of patients with MS have cognitive impairment—most commonly, problems with processing speed and episodic memory—the exact mechanisms behind such impairment are unclear.
“Studies of MRIs that look at brain atrophy in MS provide very little and limited validity in terms of predicting who will have cognitive impairment,” Dr. DeLuca said. “If you look at brain atrophy and at cognitive impairment, the correlation is not really high. Well, why not?”
To answer this question, the researchers looked to the cognitive reserve hypothesis, which postulates that intellectual enrichment is associated with greater cerebral efficiency and provides a bulwark against cognitive impairment. In Alzheimer’s disease, this hypothesis is supported by multiple studies finding that lower educational attainment is a risk factor for dementia.
“Greater enrichment in life somehow creates this reserve that protects against the expression of cognitive impairment, even with the same degree of pathology,” Dr. DeLuca explained. “So when disease challenges cerebral functioning, patients with greater premorbid cerebral efficiency or cognitive reserve can withstand more advanced disease before suffering cognitive impairment.”
Cerebral Efficiency
The researchers began their investigation of cognitive reserve in MS by studying 58 patients with MS and 43 healthy controls. They estimated the participants’ cognitive reserve based on a word-reading proxy of premorbid intelligence (the Wide Range Achievement Test–3). In addition, they administered tests of simple processing efficiency, complex processing efficiency, and verbal learning and memory to all participants.
Patients with MS and lower cognitive reserve showed very significant cognitive deficits relative to controls with regard to complex processing efficiency and verbal learning and memory, the researchers found. In contrast, patients with MS and higher cognitive reserve showed no impairments relative to controls.
“So this first study showed us that the cognitive reserve hypothesis existed in persons with MS—there’s a protective factor,” Dr. DeLuca concluded.
Atrophy and Information Processing
In their second study, the researchers focused on whether cognitive reserve moderates brain atrophy’s effects on information processing efficiency in MS.
They recruited 38 patients with MS and used the Wechsler Abbreviated Scale of Intelligence (WASI) vocabulary subtest to estimate patients’ premorbid intelligence. In addition, they used a composite score of the Symbol Digit Modalities Test and the Paced Auditory Serial Addition Task to determine the patients’ information processing efficiency. Subjects underwent higher resolution brain MRI, and third ventricle width was used as a measure of their brain atrophy.
Brain atrophy predicted worse information processing efficiency, cognitive reserve predicted better information processing efficiency, and these effects were moderated by an interaction between atrophy and cognitive reserve, the researchers found.
“Among persons with higher reserve, even as you increase to a high level of brain atrophy, there is a protective effect against the expression of cognitive impairment,” Dr. DeLuca noted. “Well, compare that to persons with lower reserve. As you increase brain atrophy, you’re showing a very significant drop in cognitive function—almost three standard deviations lower, and that’s huge. I think cognitive reserve is demonstrating a protective effect against the expression of these disease pathologies.”
Atrophy, Learning, and Memory
Next, the researchers looked at the relationship between cognitive reserve, learning, and memory in MS. They used the WASI vocabulary test to estimate lifetime intellectual enrichment in 44 patients with MS. The patients’ degrees of learning were estimated with total learning across trials of the selective reminding test (SRT), their degrees of memory were estimated with SRT 30-Minute Delayed Recall, and their brain atrophy was determined by third ventricle width.
Although brain atrophy was associated with worse learning and memory, these effects were moderated by cognitive reserve, with greater reserve lessening atrophy’s negative effects. “Among patients with higher reserve, there’s essentially no change, even with the increase in pathology,” Dr. DeLuca noted. “Patients with lower reserve, however, are showing a decline in performance. We find the same thing in processing speed and in immediate recall.”