Zvinka Z. Zlatar - US grants

? DESCRIPTION (provided by applicant): Research efforts focusing on maintaining brain and cognitive health in aging have become a critical public health concern given that the number of people over 65 will increase from 40.2 million in 2010 to 88.5 million by 2050 in the United States, with a forecasted AD prevalence of 13.8 million. It is crucial for health professionals to develop behavioral interventions that prevent cognitive decline in healthy older adults. Cardiovascular risk factors have been associated with cognitive decline, and cerebrovascular changes are very common in normal aging, suggesting that targeting cardiovascular risk factors could potentially help to maintain cerebrovascular and cognitive health. Physical activity interventions conducted in supervised settings (laboratories and group settings) with older adults have consistently shown improved cardiovascular and cerebrovascular health and improved cognitive function. What is lacking is the development of interventions that take place in real world environments and that take advantage of new technologies to help objectively track real time physical activity behaviors. Real world physical activity interventions have the potentia to reach a larger segment of the population and to enhance maintenance after the intervention period ends. The proposed research project will develop a novel, 6-month physical activity intervention using mobile health technologies to promote physical activity levels likely to affect cerebral blood flow and cognition in real world environments in cognitively normal older adults aged 65-75. The goal of this intervention is to increase time spent in moderate to vigorous physical activity to 150 min/week, which is recommended by the American Heart Association for cardiovascular benefits. For this purpose, a randomized controlled trial will be conducted with 30 participants being assigned to the mobile health physical activity condition and another 30 to an education control condition for 6 months. Physical activity prescriptions will target 60-75% of each individual's maximum heart rate based on fitness testing and will be conducted independently in real world environments. Moreover, we will investigate if this novel intervention has the potential to increase cerebral blood flow and improve cognition as has been shown by previous research in controlled environments. This five year K23 application is designed to provide the applicant with the necessary training to become an independent clinical scientist focusing on developing behavioral interventions to improve brain and cognitive aging. This project builds on the applicant's previous experience with cognitive neuroscience of aging, brain imaging, and neuropsychology to achieve the following training goals: 1) Obtain extensive training in the development and implementation of physical activity interventions with older adults using mobile health technology; 2) learn how to collect, process and analyze cerebral blood flow and resting state connectivity brain imaging data; 3) develop expertise in the design and implementation of randomized controlled trials (including advanced statistics); and 4) obtain experience with scientific writing and grantsmanship. Completion of this project and associated training goals will ensure the applicant obtains the necessary skills and experience to transition into the role of an independent investigator who integrates the fields of exercise science, real world behavioral interventions, cognitive enhancement, and brain imaging with older adult populations.

Project Summary/Abstract This project is directly aligned with the NIA?s strategic goals of 1) developing improved approaches for the early detection and diagnosis of disabling illnesses and age-related debilitating conditions and 2) identifying appropriate strategies for disease, illness, and disability prevention and healthy aging among the underserved. As the older adult population continues to grow, it is expected that an increasing number of seniors will be living with Alzheimer?s disease and related dementias. As such, it is imperative to identify early risk markers of cognitive decline prior to symptom manifestation. Although Hispanics/Latinos (henceforth referred to as Hispanics) are at increased risk for mild cognitive impairment compared to non-Hispanic Whites, research investigating early risk markers in this growing and underserved segment of the United States (U.S.) population is lacking. One potential early risk marker of Alzheimer?s disease is subjective cognitive decline (SCD), which is used to describe self- reported perceived changes in cognitive function compared to a previous state. Although the expression, reporting, and predictive value of SCD may vary due to factors such as cultural/ethnic background, acculturation, and education level, little research has been conducted outside of non-Hispanic White cohorts. In fact, most existing SCD research with Hispanics has been conducted in Spain, whose population is very culturally different than Hispanics living in the U.S. The proposed study will help advance SCD research by characterizing the cognitive and biomarker correlates of SCD in U.S. Hispanics cross-sectionally, and by establishing its predictive value for cognitive change over three years. To achieve this, we will prospectively administer a validated SCD questionnaire, a culturally sensitive cognitive test battery, mood questionnaires (i.e., depression), and culturally- relevant measures that may influence SCD to older Hispanics with normal cognition (N=100) or mild cognitive impairment (N=100). We will also obtain SCD reports from participant?s informants to determine its differential ability to predict cognitive decline. Participant recruitment will leverage on existing cohorts at two sites: The University of California San Diego Shiley-Marcos Alzheimer?s Disease Research Center (ADRC) and the 1Florida ADRC. We will investigate if self and informant SCD reports are associated with concurrent, objective cognitive function (adjusting for relevant covariates) and examine if baseline SCD reports predict change in cognition over 3 years. Moreover, we will use existing biomarkers collected by the ADRCs, as well as novel blood-based biomarkers, to investigate if SCD is associated with amyloid-? and apolipoprotein E ?4 allelic status. Furthermore, we will investigate if acculturation, health literacy, country of origin, and language of testing, as well as demographic variables (age, sex, years of education) influence SCD reporting. Findings will characterize the cognitive and biomarker profile and predictive value of SCD in U.S. Hispanics, help refine SCD measurement, and identify individual differences in SCD reporting that may confer greater risk for decline.