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NEWS FROM THE INTERNATIONAL STROKE CONFERENCE: Chronic Infections Linked to Vascular Dementia, Cognitive Decline

Susman, Ed

doi: 10.1097/01.NT.0000446133.70205.34
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In a preliminary study, investigators reported that individuals who were exposed to diseases such as herpes, chlamydia, and Helicobacter pylori , tended to have lower performance on memory and other cognitive tests, but after adjustment for socioeconomic status and other factors, the differences did not reach statistical significance.

SAN DIEGO — Individuals with a high infectious disease burden with conditions associated with incident stroke appear to suffer declines in executive functioning and memory, researchers reported here at the annual International Stroke Conference sponsored by the American Heart Association/American Stroke Association.

In a preliminary study, individuals who showed exposure to diseases such as herpes, chlamydia, and Helicobacter pylori, tended to have lower performance on memory and other cognitive tests, but after adjustment for socioeconomic status and other factors, the differences did not reach statistical significance, said Clinton B. Wright, MD, scientific director at the McKnight Brain Institute at the University of Miami.

In his study, when variables such as age and sex were used, there was a statistically significant (p=0.03) relationship between infectious burden and memory functioning, Dr. Wright reported here. However, when factors such as education and insurance were included in the model, the significance was attenuated (p=0.06); when adjusted for vascular risk factors the significance was again reduced (p=0.07).

Processing speed approached significance when adjusted for age and sex (p=0.06) but that trend was attenuated when modifiable risk factors were put into the model equation (p=0.26), the researchers reported.



“We found that, essentially, the higher your infectious burden, the lower your cognitive performance was at the time of the initial assessment,” Dr. Wright said. “Those findings were weakened when we adjusted for socioeconomic factors such as age and education. After adjustment, there was a general trend for an association; when we looked at decline in performance over time on the tests, we again found that a higher infectious burden was associated with more decline, but again when we adjusted for things it was weakened and did not reach statistical significance.”

The study relied on information accrued in the Northern Manhattan Study, a longitudinal, community-based study of study of stroke and stroke risk factors in the Northern Manhattan area. Dr. Wright and colleagues enrolled 588 individuals and followed them for a mean of six years.

The researchers enrolled individuals who had never been diagnosed with stroke, who were more than 40 years old, and who had resided in Northern Manhattan for at least three months. When contacted by random-digit dialing, 91 percent of the people contacted agreed to be included in the study; eventually, 69 percent of the individuals contacted were included in the research project.

The infectious burden was developed to determine exposure to certain pathogens, Dr. Wright explained. A composite index of serologic measures of exposure to H. pylori, Chlamydia pneumoniae, herpes simplex virus I and II, and cytomegalovirus has previously been associated with incident stroke, carotid plaque thickness, and global cognitive performance, he said.

Dr. Wright and colleagues at Columbia University in New York created a weighted index where the risk that each of the pathogens was associated with stroke was taken into account. “We looked to see if this weighted index of infectious burden was associated with cognitive performance at baseline and after an average of about six years follow-up,” Dr. Wright said.

“The measurements we make tell us people were infected at some point — it doesn't tell us when and we don't know if they were symptomatic,” he told Neurology Today. “Many of these infections can be asymptomatic and some are annoyingly symptomatic such as herpes simplex virus 1, which results in cold sores, but you don't really think about being infected. H. pylori, which we know can cause ulcers, is more serious but many people are colonized with H. pylori and they never get an ulcer.”

Dr. Wright said that the researchers are planning to expand the number of individuals tested in the study. “We are reporting preliminary data. We observed a trend that memory was impacted by infectious burden. In general, all the domains were going in that expected direction. We aren't saying that their performance reached the level of impairment, but it was worse relative to people who had a lower infectious burden,” he said.



“We think that infection with these agents leads to immune responses and inflammation that damages blood vessels and causes vascular disease; this then damages the brain and causes these lowered cognitive outcomes,” Dr. Wright said. “We haven't proven that in this study. This is just an observational study that needs to be replicated.”

What to do with the findings is another matter, he said. “We also have to determine whether treating patients to eliminate the infections changes outcomes. We don't know that and we are still pretty far away from knowing that. We need to do more work to determine which organisms we have to target.”

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In commenting on the study, James C. Grotta, MD, FAAN, director of stroke research at the Center for Innovation and Research at Memorial Hermann Hospital of Texas Medical Center in Houston, told Neurology Today: “There has been a relatively consistent relationship observed between the incidence of systemic infections and the incidence of vascular events such as heart attacks. It is not unreasonable to think that other manifestations of cerebrovascular disease aside from stroke syndromes would also be associated with cognitive impairment.”

This is an interesting observation, said Dr. Grotta, who serves on the Neurology Today editorial advisory board. “The implication of this work is that if you have hypertension and high cholesterol — vascular disease risk factors — you may be at risk of developing strokes or vascular dementia. In these patients, risk factor control can be important and if this systemic infection is found, anti-inflammatory treatment may be important. Inflammation is associated with the more garden variety type of stroke, but it's also possible that inflammation may be involved in this other type of process that results in dementia.”

Dr. Grotta added: “It is possible that inflammation has an effect on the vasculature that leads to small vessel strokes. We believe that cognitive impairment may actually be small, subclinical strokes and the cause of those strokes may be different than the cause of the bigger strokes. There are patients who never have clinical strokes that also suffer dementia and they have a lot of ischemia that affects white matter. We don't really understand what the pathology of that kind of vascular dementia is. We are just beginning to understand that.

“If we want to reduce stroke and vascular cognitive impairment beyond what we are doing now, we may have to go after inflammation,” he said. “A clinical trial to combat inflammation in these patients with high infectious disease burden with agents such as statins — which have benefits beyond lowering cholesterol — may be warranted.”

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•. Neurology Today: Herpes zoster identified as potential risk factor for vascular disease.
    •. Neurology archive on vascular risk factors and cognition:
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