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National Institute of Environmental Health Sciences

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Researchers Build Capacity for Study of Dementia and Risk Factors in Kazakhstan

By Elizabeth Witherspoon, Ph.D.

Through the NIH Global Brain Disorders Research Program, an international multidisciplinary team of researchers from the University of Pittsburgh and Kazakh National Medical University is building capacity for studying cardiovascular and environmental risk factors for cognitive impairment (CI) and dementia among the rapidly increasing elderly population in Kazakhstan.

NIEHS, the National Institute on Aging, and the NIH Fogarty International Center are supporting the team’s work to help ready this upper-middle income country in Central Asia to conduct research into the health effects of both cardiovascular risk factors and air pollution among the elderly (ages 60 and over). This age group is estimated to increase by 70% between 2010 and 2030. A high burden of CI and dementia is expected in Kazakhstan due to the anticipated demographic change, a high burden of cardiovascular disease (CVD), and a high level of air pollution.

Risk Factors Include Air Pollution

“Mortality from CVD in Kazakhstan is the second highest in the world,” said Akira Sekikawa, M.D., Ph.D., M.P.H., overall principal investigator (PI) and associate professor and cardiovascular epidemiologist at the University of Pittsburgh.

“Kazakhstan, in general, has experienced a great increase in oil and coal production, and combustion of fossil fuel products has resulted in high pollution levels,” said Evelyn Talbott, Dr.P.H., M.P.H., FAHA, co-PI and professor and environmental epidemiologist at the University of Pittsburgh. The level of air pollution in Kazakhstan is five times that of the U.S., which research also has shown is a risk factor for CVD.

The challenge, noted Sekikawa, is that there is no Kazakh data for the midlife CVD risk factors associated with later dementia—such as high cholesterol and blood pressure, smoking, and diabetes—and the association of these risk factors is weak among the older population. So, clinicians cannot determine who among the elderly now is at most risk for late-life dementia. However, Sekikawa’s group of researchers at University of Pittsburgh has found an association between late-life measures of coronary artery calcification (CAC) and pulse wave velocity (PWV), a measure of arterial stiffness, well-established biomarkers of coronary atherosclerosis which result from cumulative exposure of earlier midlife risk factors, and dementia. Therefore, CAC and PWV can serve as biomarkers among older patients to identify who is most at risk for CI and dementia. No previous epidemiological study has examined these measures in Kazakhstan, however.

Furthermore, several epidemiological studies show a significant association of air pollution with CI and dementia. Very small particles of PM2.5 (particulate matter less than 2.5 micrometers in diameter, or 3% of the size of a human hair) can cause an acute myocardial infarction, or heart attack. They also get into arterial beds and create inflammation that, over time, leads to atherosclerosis, or buildup within arteries that block blood flow, explained Talbott. These effects occur all over the body, including across the blood-brain barrier, and damage mental acuity. She said research has established associations between long-term exposure to PM2.5 air pollution and dementia and Parkinson’s Disease.

Evelyn Talbott, Dr.P.H., M.P.H., FAHA, Akira Sekikawa, M.D., Ph.D., and Shalkar Adambekov, M.Sc. in the office.

(L-R): Talbott, Sekikawa, and Shalkar Adambekov, M.Sc., doctoral student, all from the University of Pittsburgh, discuss details of the study. Adambekov is a physician from Kazakhstan who plays a key role on the project as liaison between the U.S. and Kazakh teams.
(Photo courtesy of University of Pittsburgh)

“With the limited number of studies that reported the association of air pollution with CI/dementia, our study will provide important data in this area in the future,” said Talbott.

The research teams will work together to collect individual data from 400 inhabitants of Almaty ages 60 and over to determine the normative values of the series of neuropsychological tests. Almaty is Kazakhstan’s former capital and largest city, with a population of 1.7 million. Concurrently, they will leverage daily air pollution data from Almaty’s six air monitoring stations to estimate individual levels of air pollution exposure using participants’ home addresses.

They will use the Mini-Mental State Exam, a commonly used questionnaire in the U.S. for screening, followed by several other neuropsychological tests that are commonly used to diagnose CI and dementia in the U.S. Although Russian-Kazakhstan versions of these neuropsychological tests are available, clinically these are rarely used and normative values of these tests to assess the burden of CI and dementia have not been set.

Beth Snitz, Ph.D., associate professor of neurology and associate director of the Alzheimer Disease Research Center Clinical Core at the University of Pittsburgh, and Saule Turuspekova, M.D., Ph.D., neurologist and professor at Kazakh National Medical University, will lead the neuropsychological assessments. Ussen Kenessariyev, M.D., DMs, Ph.D., a professor at S.D. Asfendiyarov Kazakh National Medical University, will collaborate with Talbott on the air pollution portion of the study.

This international team of investigators is planning to apply the obtained data and transferred technologies to a future national biobank project in Kazakhstan in which a population-based sample of 25,000 subjects will be enrolled to accurately evaluate the burden of CI and dementia as well as the association of air pollution, PWV, and CAC with CI and dementia.