Impaired Executive Function Linked With Subsequent Stroke By Susan Jeffrey
Medscape Medical News
February 10, 2010 — A new study finds that among men older than 70 years, poor performance on the Trail Making Test B, a cognitive test that reflects impaired subcorticofrontal activity or executive function, is associated with future stroke risk.
"Our results indicate that the risk of brain infarction is increased already in the subclinical phase of milder cognitive dysfunction, which may be an indicator of unrecognized cerebrovascular injury," the researchers, with first author Bernice Wiberg, MD, from Uppsala University, Sweden, conclude.
The results also suggest that the Trail Making Test B, a simple, timed pencil-and-paper test in which subjects are asked to connect dots in a 1-A-2-B pattern, may be a useful screening tool in the clinic, senior author Johan Sundstrom, MD, also from Uppsala University, told Medscape Neurology.
"It's an observational study, so we can't talk about causality, but we do want to identify people as early as possible who are at risk for stroke, and this test is easy and cheap, even cheaper than an ECG [electrocardiogram] or cholesterol level, so that should make it very accessible," Dr. Sundstrom noted, although more study is needed.
Their report is published in the February 2 issue of Neurology. Vascular Risk
Cerebrovascular risk factors and biologic aging have been associated with white matter lesions and silent cerebral infarctions, as well as clinical stroke, the study authors write. Several lines of research have suggested that these subclinical changes can affect cognitive function and that it is executive dysfunction, reflecting lesions in subcorticofrontal pathways, rather than memory deficits, that features prominently in early vascular cognitive impairment.
Some but not all studies have suggested increased stroke risk among those with clinically impaired cognitive function, they note. This more detailed look at the connection between changes and cognitive function, the researchers write, "is motivated especially with the purpose to find persons at high risk in the hopeful view of preventive treatment."
Dr. Sundstrom pointed out that Alzheimer's disease and vascular dementia have been shown to share some risk factors. "Some people think they are perhaps 2 sides of the same coin," he said, with Alzheimer's primarily a disease of small arteries and vascular dementia a disease of the large arteries.
"We have come to think that because cognitive function and dementia that isn't really preceded by a stroke or overt vascular disease may still be a disease of the arteries, that cognitive function tests may actually be viewed as sensitive tests of function in the small arteries," he explained.
To find out, they looked at the relationship between performance on tests that specifically looked at subcorticofrontal function, the Mini-Mental State Examination (MMSE) and the Trail Making Tests A and B, and subsequent incidence of fatal or nonfatal stroke or transient ischemic attacks (TIAs) and stroke subtypes, using a population-based cohort called the Uppsala Longitudinal Study of Adult Men.
This sample of 930 men, who were all 70 years old at baseline for this analysis, has been followed up since they were 50 years of age. All were free of previous stroke or TIA, and all underwent testing using the 3 cognitive tests at that time.
During 13 years of follow-up, 166 men had a stroke or TIA, 105 of these with ischemic strokes.
"Basically what we found was somewhat supportive of our hypothesis," Dr. Sundstrom said. "Of the 3 cognitive function tests, the Trail Making Test B captured stroke risk."
After adjustment for education, social group, and traditional cardiovascular risk factors, each standard deviation increase in the Trail Making Test B completion time was associated with an increased risk for brain infarction, and those in the lowest quartile for performance on this test had a more than 3-fold increased risk. Table. Stroke Risk Associated With Performance on Trail Making Test B
Endpoint
Hazard Ratio (95% Confidence Interval)
1-SD increase in Trail Making Test B time
1.48 (1.11 – 1.97)
?
There was no relationship between Trail Making Test B performance and stroke outcomes overall or with hemorrhagic stroke risk. No relationship was seen between performance on the Trail Making Test A test or the MMSE and any stroke outcome.
The difference may lie in the specific aspects of cognition these tests are measuring, Dr. Sundstrom said. The MMSE, for example, is a good test for capturing clinical dementia.
"I would say that the explanation that we had that the MMSE was not really a strong predictor of stroke in our cohort was that the participants were pretty healthy and had pretty high scores on the MMSE," he added. "It's just possible that the Trail Making Test B was a more sensitive measure in this high cognitive function range that we had in our cohort. It's possible the MMSE might have been better if you had people with a lower cognitive function to start with."
There are numerous cognitive function tests, he added, and it remains to be determined which might be the best at identifying stroke risk, Dr. Sundstrom added. Further, there may be other risks besides stroke, such as mortality risk or risk for myocardial infarction, that might also be identified using tests of cognitive function. The study was supported by grants from the Medical Faculty at Uppsala University, STROKE-Riksforbundet, the Swedish Research Council, the Swedish Heart Lung Foundation, the Geriatric Fund, and Uppsala Association against Heart and Lung Disease. Dr. Sundstrom serves on a scientific advisory board for Itrim. Financial disclosures for the coauthors appear in the original article. Neurology. 2010;74:379-385.
