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SAN DIEGO—If a patient is cognitively impaired, will that have an effect on his or her chances for recovery after stroke? Not necessarily, according to a new study presented here at the Annual Meeting of the American Neurological Association.

“With or without cognitive impairment, patients improved at a similar rate,” said Larry B. Goldstein, MD, who led the study, in an interview after his presentation. “At least in this population, it didn't really matter. The rate of improvement in terms of neurological impairments was similar regardless of whether patients had cognitive impairment at baseline or didn't.”

Instead, patients' cognitive impairment was correlated with their overall level of neurological impairments at each point in time, said Dr. Goldstein, Professor of Neurology and Director of the Center for Cerebrovascular Diseases at Duke University School of Medicine in Durham, NC.

He and his co-investigators analyzed data from the Amphetamine Enhanced Stroke Recovery (AESR) study, an ongoing NIH-sponsored pilot study that determine whether di-amphetamine combined with physical therapy has a stronger impact on post-stroke motor recovery than physical therapy alone. In this double-blind, placebo-controlled study, the investigators randomized patients to receive either di-amphetamines and physical therapy or physical therapy alone.

One of the secondary goals of AESR was to determine the impact of cognitive impairments on the degree and rate of improvement of stroke-related deficits. The investigators used the cognition subscale of the Folstein Mini-Mental State Evaluations (MMSE) to assess cognitive impairment and the impairments subscale of the NIH-Stroke Scale (NIH-SS) – which measures the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss – to assess overall neurological impairment and severity of stroke-related deficits. The investigators obtained the MMSE and NIH-SS scores at the beginning and end of rehabilitation and at 90 days. An MMSE score of less than 24 indicated cognitive impairment.

When asked whether depression could have influenced outcome in the trial, Dr. Goldstein noted that the investigators had actually conducted a separate analysis and presented the results at the 2005 AAN Annual Meeting. At the beginning of rehabilitation, 11.5 percent of patients were depressed and 36 percent had mild mood disorders, he said. At baseline, depressed patients had more severe deficits than those without depression. Adjusting for both age and baseline NIH-SS, NIH-SS at 90 days was independently related to the presence of depression at baseline. “So, depression – but not the level of cognitive impairment as reflected by the MMSE – was related to recovery,” Dr. Goldstein said. “We have not yet analyzed the relationship between cognitive impairment and depression.”


The study involved 72 subjects who were an average of 65 years old. Fifty-five percent were men, and 79 percent were white, with 15 percent African- American and 6 percent other ethnicities. The investigators categorized strokes by anatomic location: 37 percent of strokes were lacunar, 58 percent were partial anterior, and 4 percent were total anterior circulation strokes.

Forty-nine percent of these patients had some level of cognitive impairment at baseline. In the group overall, the MMSE improved from an average of 20.7 at baseline to an average of 22.9 at discharge. This improvement was statistically significant at a probability value of less than 0.0001. After this, the improvement plateaued, Dr. Goldstein said.

The NIH-SS score averaged 12 at baseline and continued to drop in an inverse relationship to the rise in MMSE score, so that at the end of the study the average NIH-SS was less than 10. As with the MMSE, the improvement in NIH-SS from baseline to discharge was statistically significant at a probability value of less than 0.0001.

In patients with cognitive impairment, the NIH-SS was an average of 18 at baseline and 12 at the study's end. In those with normal cognition, the NIH-SS scores averaged 10 at baseline and approximately 6 at the study's end. Although the MMSE and the NIH-SS correlated at each time point, there was no correlation between the baseline NIH-SS score and the final MMSE, Dr. Goldstein stressed.

“The recovery rate or final level of neurological impairment was independent of baseline cognitive impairment,” he said. “The cognitive impairment improved over time.”

Why would cognition improve post-stroke? Stroke-related neurological impairments tend to improve – but to varying degrees depending most importantly on the severity of the deficit – Dr. Goldstein explained, adding that cognitive impairments are no different.


“This analysis reflects a new trend in clinical trials regarding stroke,” said Gustavo Roman, MD, in a phone interview. Dr. Roman, who was not involved in the study, is Professor of Medicine and Neurology at the University of Texas Southwestern School of Medicine in San Antonio, where he is the Director of the Memory Disorders Clinic.

The study is important because it assesses both motor capacity and cognitive function, Dr. Roman said. “Maybe a message here is that physical therapy benefits cognitive measures,” he said. “In my practice as a neurologist, I have observed movement from the defeatist approach of dismissing patients post-stroke to nursing homes to optimism that there could be improvements through physical therapy. Including an assessment of cognitive impairment adds a new dimension, the retention of cognitive function after stroke. That issue is overlooked in large trials.”

The investigators have shown that taking action to preserve cognitive function is effective,” Dr. Roman said. In that regard, he added, AERS may eventually have a pioneering impact on the approach to post-stroke cognitive functions.


  • ✓In a secondary analysis of data from the Amphetamine Enhanced Stroke Recovery study, investigators reported that the rate of motor improvement in patients after stroke was similar regardless of whether patients had a cognitive impairment at baseline and that cognitive impairment was correlated with their overall level of neurological impairments at each point in time.