Stroke Linked to Accelerated Cognitive Decline

Fran Lowry

July 09, 2015

Incident stroke is associated with acute decline in cognitive function and also accelerated and persistent cognitive decline over 6 years, new research shows.

Investigators at the University of Michigan, Ann Arbor, found incident stroke was associated with acute decline in global cognition, new learning, and verbal memory and that it accelerated over time.

"Stroke is known to be associated with acute cognitive decline, but it was unclear whether stroke survivors acquire a faster rate of cognitive decline over the years following the event," lead author Deborah A. Levine, MD, MPH, told Medscape Medical News.

The study was published in the July 7 issue of JAMA.

Altered Trajectory

Dr Levine noted that the current study is novel in that it is the first to monitor cognitive function in a longitudinal manner before and after stroke.

"The results show that patients are on a different path of faster decline after the stroke which appears to be linear in that it does not seem to level off. That is in addition to the acute drop that occurs at the time of the stroke. We found that the stroke acted like a switch to a different trajectory of cognitive decline," she said.

The investigators examined the changes in cognitive function among survivors of a first stroke, controlling for their prestroke trajectories.

The prospective study included 23,572 participants from the United States age 45 years or older without cognitive impairment at study entry, which was between 2003 and 2007.

The participants, who were part of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, were followed through March 2013.

All participants underwent cognitive function tests administered by telephone, including the Six-Item Screener to assess global cognition and assessed annually. They also underwent a battery of cognitive tests administered biannually. These included the Consortium to Establish a Registry for Alzheimer Disease, Word List Learning, Word List Delayed Recall, and Animal Fluency Test.

During a median follow-up of 6.1 years, 515 participants (306 white, 209 black) survived incident stroke and 23,057 were stroke free.

Results showed that patients with stroke had accelerated and persistent declines in global cognition (0.06 points per year faster) and executive function (0.63 points per year faster) compared with those without stroke, after accounting for individuals' cognitive changes before and acutely after the event.

Stroke patients also had a significantly faster rate of incident cognitive impairment following stroke compared with prestroke rates (odds ratio, 1.23 per year), controlling for the odds of developing cognitive impairment before or acutely after the event.

Predicted Mean Change in Global Cognition Scores Before and After Acute Stroke. Source: JAMA. 2015;314:41-51

"As an example, for a 70-year-old black woman with average values for all covariates at baseline, stroke at year 3 was associated with greater incident cognitive impairment. The absolute difference at year 3 was 4 percent, and at year 6, it was 12.4 percent," noted Dr Levine.

Need for Long-term Monitoring

"Doctors can tell their patients that they warrant early monitoring of their cognitive function over the short term, and also the long term after their stroke. There is no agreed-upon standard definition of long term, but we found changes persisting over 6 years, so we have got to monitor these patients for longer. That's the big policy change," she said.

Currently the guidelines recommend that stroke survivors be screened for cognitive problems when they are in the hospital for their stroke and then early after stroke, usually in the first few months after stroke. "Our study results suggest that stroke survivors should be monitored for years," Dr Levine said.

"We should also monitor them to help to control their risk factors so that they don't have another stroke. That is vital. Up to 80 percent of strokes can be prevented so it's crucial to implement effective strategies that control risk factors and reduce the risk of stroke. So adopting a healthy lifestyle, controlling high blood pressure, diabetes, high cholesterol, and engaging in healthy lifestyles and behaviors, like avoiding smoking and exercising," said Dr Levine.

In an accompanying editorial, Philip B. Gorelick, MD, MPH, and David Nyenhuis, PhD, from the Michigan State University College of Human Medicine, Grand Rapids, suggest these new findings may provide an opportunity for intervention immediately following stroke to prevent accelerated stroke-related cognitive decline.

"This study tells us that stroke is not just an acute event —– the damage continues and it appears to be a long-term process. This gives us the opportunity of trying to intervene to slow this process down. We need to have a more upstream focus. We need to find out what sets this train of events into motion, and very important, can we stop it," Dr. Gorelick told Medscape Medical News.

In their editorial, Dr Gorelick and Dr Nyenhuis also support screening for cognitive impairment over the long- term following stroke and suggest that clinicians could use the Montreal Cognitive Assessment, which they say is "valid, easy to administer and highly sensitive."

"Information gained from cognitive screening can be used to plan for daily management of patient care based on cognitive performance and need for possible formal neuropsychological testing. In addition, intensification of vascular risk management may be indicated for patients at risk of cognitive impairment in an attempt to prevent subsequent stroke, myocardial infarction, loss of cognitive vitality, and overall disability," they add.

Potential Mechanism?

Dr Levine said important next steps will include understanding what is going on with the mechanism behind this accelerated decline and to try to intervene to see whether it can be slowed.

The researchers suggest that stroke may cause long-term cognitive decline through several mechanisms. "Stroke may induce or exacerbate neurodegenerative disease, or neurodegenerative disease may amplify brain injury and cognitive deficits after stroke. Vascular risk factors or an immune response may cause ongoing cerebrovascular injury, inflammation, and oxidative stress."

Dr Gorelick proposed that the mechanism may involve inflammatory processes.

"The brain has its own inflammatory mechanisms mediated by microglial cells. We need to investigate this and other possible mechanisms."

He added that there may also be a synergistic effect with Alzheimer's pathology.

"We know that Alzheimer's changes occur 15 to 20 years before the clinical manifestation of the disease. If you add in a stroke then this may create a synergism that accelerates the process.

This work was supported by a cooperative agreement from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services, and National Institute on Aging. Dr Levine, Dr Gorelick, and Dr Nyenhuis have disclosed no relevant financial relationships.

JAMA. 2015;314:41-45. Abstract Editorial


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