Global Collaborative Research on Establishing a Korean Cognitive Aging Cohort

Global Collaborative Research on Establishing a Korean Cognitive Aging Cohort That is Associated With the Einstein Aging Study

The goal of this observational study is to learn how daily emotional stress affects cognitive function and inflammation in community-dwelling older adults aged 60 and older in Seoul, Republic of Korea. The main questions it aims to answer are:

Does daily psychological stress measured in real-time affect short-term and long-term cognitive function in older adults? Do pro-inflammatory cytokines (such as CRP, IL-6, IL-10, and TNF-α) mediate the relationship between emotional stress and cognitive decline? How do social support and social isolation influence cognitive function and inflammatory biomarkers over time?

Participants will:

Complete baseline surveys assessing depression, cognitive function, and personal characteristics Use a smartphone app to answer brief surveys about their emotions, cognitive performance, and social interactions 1-6 times daily for two weeks Wear a Galaxy Watch to track sleep quality, heart rate, and physical activity Provide blood samples for inflammatory biomarker analysis Return for follow-up assessments at 6 months and 1 year

This study is part of an international collaboration to establish a Korean cohort comparable to the U.S. Einstein Aging Study, with the aim of developing culturally tailored dementia prevention strategies.

A. Final Goal

• This study aims to identify the interactions between physiological, psychological, social, and cultural-environmental factors that influence the maintenance and decline of cognitive function in aging of socially vulnerable older adults. By doing so, it seeks to reduce the societal burden of cognitive decline in older adults and provide a foundation for effective interventions to manage dementia risk.

• The principal investigator's research team at Korea University's Department of Public Health Sciences and the team led by Professors Jennifer Graham-Engeland and Christopher Engeland from Penn State University (co-leaders of the Einstein Aging Study under NIH P01), aims to establish a protocol for the domestic cohort of the Einstein Study of Aging and conduct cross-national comparative research. The specific objectives are:

  1. Develop a Korean cohort protocol that is comparable to the Einstein Aging Study based on the principal investigator's existing community-based cohort studies with socially vulnerable older adults.
  2. Investigate the impact of real-time psychological stress (Ecological Momentary Assessment; EMA) on real-time and long-term cognitive function and examine the mediating effects of pro-inflammatory cytokine biomarkers through data collection in Korea.
  3. Compare Korean older adult data with the U.S. Einstein Study panel to study the influence of annual levels of social support and isolation on cognitive function and biomarkers, exploring the moderating effects of socio-environmental and cultural factors.

• Through this research, the principal investigator and international collaborators aim to utilize their expertise in real-time daily emotional and cognitive function measurements and inflammatory biomarker protocols. By integrating psychological research methodologies, the study seeks to elucidate the biological-neuropsychological mechanisms of how emotional stress impacts neuroinflammation and cognitive regulation in older adults. This will establish a foundation for developing dementia prevention and cognitive rehabilitation programs tailored to the Korean cultural context.

B. Research Design and Overview

1. Korean Cohort Design that is comparable with the Einstein Aging Study

   • The study adopts the Burst Cohort Design utilized by the U.S. Einstein Aging Study (EAS) for longitudinal analysis. To explore causal relationships and the role of mediators, a minimum of three repeated measurements-baseline, six-month follow-up, and one-year follow-up-will be conducted.

   • The Burst Cohort Design involves short-term (daily) and long-term (annual) assessments. Daily changes, such as emotional states and cognitive performance, will be captured via mobile app-based surveys and stress biomarker sampling over two weeks. Long-term changes will be assessed through annual follow-ups.

2. Participant Recruitment and Incentives

   • Following IRB approval, socially vulnerable older adults (recipients of social welfare support due to economic poverty and social isolation) will be recruited through the Seongbuk Senior Welfare Center in Seoul, Republic of Korea. Training sessions on smartphone EMA will be provided as part of smartphone classes. Participants will receive tokens of appreciation and dementia prevention seminar opportunities.

     1) Participant Selection Criteria

   • Inclusion: Community-dwelling older adults aged 65 or above.

   • Exclusion: Individuals diagnosed with dementia or those with sensory, cognitive, or physical impairments that hinder survey and EMA participation.

     2) Two-Week EMA Protocol

   • During the two-week intensive survey period, baseline surveys will assess depression, mild cognitive impairment, and other participant characteristics. Daily changes in emotional state, cognitive function, and social interactions will be measured via smartphone-based EMA surveys conducted 1-6 times daily.

   • EMA minimizes recall and response biases, enabling precise quantification of intra-individual changes. Custom apps incorporating voice-assisted surveys and integration with Galaxy watch for sleep quality, heart rate variability, and physical activity data will be used, alongside cognitive tasks from the EAS protocol.

     3) Pro-Inflammatory Cytokine Signaling Measurement

   • In collaboration with Korea University Anam Hospital, clinical diagnosis and biomarker collection for cognitive impairment will be conducted. Serum samples will be centrifuged within one hour and stored at -80°C.

   • The samples will be sent to Penn State for analysis using the EAS protocol, targeting CRP, IL-6, IL-10, and TNF-α markers via multiplex bioassays. Additional cortisol ELISA and ApoE genetic variation analyses will be performed.

C. Expected Impact and Merit to the society

1. Utilization Plans

   ① Policy and Program Development:

   • Insights from the study's findings on the bio-psycho-social mechanisms of cognitive decline in aging can inform policies and interventions for dementia prevention and management in a rapidly aging society.

     • Advancement of National Dementia Research:

   • Through international collaboration, the study will enhance methodologies and content for national cognitive aging and dementia research, leveraging the extensive experience of the Einstein Aging Study. Also, the current study will provide evidence for optimizing dementia prevention-related health services for socially vulnerable older adults.

2. Anticipated Merits

   • Scientific and Technological Merits:

     • The study will provide a foundation for innovative elderly care models, linking digital sensing technologies with cognitive health monitoring. It could support the development of remote dementia prevention and management services for community and residential care settings.

       • Economic, Industrial, and Social Merits:

     • By understanding multidimensional mechanisms accelerating cognitive aging, the study will contribute to the integration of family and community-based elderly care, improvement in dementia diagnosis and prevention programs, reduction in family caregiving burdens, and enhancement of societal quality of life.

Inclusion Criteria:

• Adults aged 60 or older residing in the Republic of Korea
• Samsung Galaxy smartphone users capable of using smartphone applications
• Sufficient cognitive ability to understand and follow research instructions (MMSE score of 21 or above)
• For individuals who do not meet the cognitive criteria, those who understand the study procedures and provide informed consent along with their legal guardian

Exclusion Criteria:

• Diagnosis of dementia at baseline
• Severe visual or hearing impairments that prevent participation in psychological assessments
• Illiteracy that prevents participation in cognitive testing
• Less than 80% compliance with the 2-day preliminary EMA protocol (one additional attempt allowed after re-training)
• Current alcohol or substance abuse
• Inability to ambulate or psychiatric conditions that prevent survey participation
• Currently undergoing cancer treatment or received chemotherapy within the past 6 months