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Phases I and II of our study focused primary on behavioral and social science factors associated with longevity and survival of cognitively-intact and community-dwelling centenarians, octogenarians, and sexagenarians. Phase III expands our research to both community-dwelling and institutionalized centenarians in our population. We strive to study a population-based sample of centenarians. Further, we expand our study to provide a balance of biomedical and psychosocial predictors of longevity and survival. As this project is currently underway, we do not have results to share. However, we do want to share the design and methods in the execution of this phase of our study.

The impetus of our current project came from the NIA Strategic Plan which articulated four major goals that NIA will pursue in the years to come. The four projects being conducted in our current NIA-funded Program Project (2001 -2007) can contribute to the eventual realization of these goals:

Project 1 will test the viability of four homologues of yeast longevity genes. Findings from Project 1 can contribute to the following NIA goals of (a) understanding healthy aging processes, (b) unlocking the secrets of aging, health, and longevity, and (c) identifying genes associated with aging, longevity, age-related diseases, and behavior.

Project 2 will test hypotheses on relationships between senile plaque/neurofibrillary tangle counts, brain infarcts, functional abilities, cognitive measures, the presence of dementia and markers of neurocognitive reserves in centenarians. Findings from this Project can contribute to the NIA goal of characterizing normal cognitive and brain function of the oldest-old.

Project 3 will test hypotheses on predictors of functional capacity, which has been shown to be an important determinant of utilization of health care resources, mortality, and institutionalization in the elderly. This Project has the potential to contribute to a number of NIA goals, including the definition of biological and environmental factors that maximize cognitive, sensory, and physical functions. This Project also aims to take advantage of the core physical health information collected on sensory, musculoskeletal, blood chemistry, mental health, and diseases of centenarians and their impact on functional capacity in comparison to control subjects in their 60s and 80s. This information can contribute to the dissociation of changes of normal or usual aging from those of diseases and disorders.

Project 4 will test hypotheses of predictors that differentiate centenarians who are independent, healthy, and experience a sense of well-being from those who are dependent, unhealthy (frail), and do not experience a sense of well-being. This Project can contribute to the NIA goal of identifying social, psychological, and lifestyle factors that promote health, well-being, and longevity.

What This Phase 3 Program Project Will Accomplish:

This Program Project is a multi-disciplinary population-based study of centenarians in North Georgia. Our long-term goal is to elucidate the roles of biological, psychological, and social factors that are pertinent to the survival and functioning of this population. We propose to develop and employ probability sampling frames to select representative samples of centenarians and of younger control populations residing in a set of designated counties in Georgia.

Projects 1 and 2 will focus on biomedical aging mechanisms among centenarians and Projects 3 and 4 will concentrate on psychosocial mechanisms. The specific aims are to:

• Assess the underlying genetic structure of our population and test initially the viability of four homologues of yeast longevity genes (LAG1Hs, PHB1Hs, c-H-ras1, and GRP78) to human longevity. Project 1
• Test hypotheses on the relationship between advanced aging and cognitive impairment by evaluating relationships among plaque/tangle counts, brain infarcts, functional ability, and cognitive measures on those participants who are willing to donate their brains. Project 2
• Test hypotheses on neuropsychological, sensory, neuromuscular, blood chemistry, mental health, and disease correlates of functional capacity among centenarians. Project 3
• Test hypotheses on the impact of distal (life events, past achievements) and proximal (individual, social, and economic resources) influences on behavioral skills and developmental outcomes (levels of adaptation) among centenarians. Project 4

How We Are Accomplishing the Goals:

The Program Project contains four projects that will focus on the same population of centenarians so that hypothesis testing on the inter-relationships among biomedical and psychosocial factors could be maximized. Five cores are employed to support the four projects.

The following figure shows the administrative structure of the Program Project and illustrates the synergistic relationships among the projects and cores:

Support Services Provided by the Cores: The cores are designed to sample, ascertain, recruit, collect and analyze data for all four projects. In so doing, we maximize the efficiency and economy in the conducting of the Program Project.

Core A is the Administrative Core. It is the command and control center for the Program Project. Core B provides the sampling frame and ascertains subjects for all four projects. Core C recruits and tests all subjects for the projects. Core D (Cell, Blood, & DNA Bank) processes and distributes the blood for analysis in Projects 1, 2 and 3. Core E is responsible for the input of data, archive, and analysis for all four projects.

Basic Data Elements Shared Across Projects: Core elements will be collected by Core C across two or more projects. These variables are employed to provide basic participant characteristics. Depending on the project, more detailed information will be obtained beyond the basic profile; the information will be used as covariates, classifying variables, or as predictor or outcome variables.

These descriptive variables are:

Synergy Across Projects: Besides the sharing of basic data elements, the projects are designed to contribute in assisting each other to better understand and account for the variability of mechanisms under investigation.

Testing Centenarians: From our experience in recruiting and testing centenarians as well as experience reported by other centenarian studies (Franke, 1977; Franke, 1985), we expect about 20 to 30 percent of the centenarians to be cognitively intact. Fifty percent will probably have dementia in varying levels of severity, and 20 to 30% will most likely be bedridden and severely demented. This variability in levels of cognitive abilities has a direct impact on all projects, as all centenarians in our population-based sample will be tested. Therefore, performance or observational measures will be used whenever possible. To address this issue, the relationships among performance, self and informant report measures are addressed in Study 1 of Project 3. Further, the relationship between informant and self reports is addressed in Project 4. Functional capacity is measured by a performance test (Lowenstein et al., 1989) in which a zero (denoting not able to perform) is a meaningful measure in Project 3. We have piloted the procedures in Project 3 with either blind, bed-ridden, or demented elders and have adjusted the procedures accordingly. We realize these measurement issues have not been adequately investigated for centenarians in the literature, and clarification of these issues is an important contribution of this Program Project.

Research Material Obtained:

Depending upon a participant’s level of involvement in the program project, information will be obtained in each of 6 clusters of information: (1) Demographics; Family and Longevity History; (2) Cognition, Neuropsychology, and Neuropathology; (3) Physical and General Health; (4) Mental Health, Personality, Resources and Adaptation; (5) Functional Capacity and Independence; (6) Genetics, Blood Chemistry and Nutrient Biomarkers.

A condition to enrollment in the program project for both the younger and centenarian cohorts is willingness to donate a small blood specimen (20 ml) and consent to its use in genetic and other blood assays. Centenarians who do not actually provide the blood specimens for the required purposes will not progress in the data collection process beyond their initial enrollment and limited demographic and cognitive screening. No additional compensation is provided for the blood specimen. All centenarian blood draws will be conducted by a physician or nurse practitioner trained in geriatric venipuncture. Younger control subject blood draws will be performed by licensed phlebotomists or nurse-practitioners.

Project 2 of the Program Project requires brain tissue donations from a subset of centenarian participants willing to prospectively consent to the donation of such tissue after their deaths. Willingness to consent to donation of brain tissue and consent to participation in Project 2 is not a condition to participation in any of the other projects. No additional compensation is offered to centenarians for the brain tissue donation. Brain tissue is not requested from the younger control subjects.

All data obtained from participants, including blood and tissue specimens, will be recorded by coded ID only; participants’ names and ID numbers will be protected, according to the guidelines established by the Institutional Review Board.

Participant Recruitment and Informed Consent Plans:

Recruitment will be performed by Core C, using the methodology and procedures therein described. Although preliminary contact with centenarians will be attempted by telephone and mail, actual recruitment will occur only in face-to-face sessions between the interviewers and the centenarian plus their caregivers/immediate family members. All informed consent procedures will comply with the guidelines, procedures, and scripts approved by the Institutional Review Board for each Project. This process includes detailed discussion of the purposes of the study, procedures to be used, confidentiality of data, and videotaping of test sessions.

For centenarian participants, joint consent procedures will be followed. Informed consents will be read and executed by the participant as well as the caregiver legally authorized to provide such consent under Georgia law. This is a sensitive area, legally and ethically. On the one hand there is the need to safeguard the presumption of autonomy and self-determination. On the other hand, there is the need to insure that the consent is truly informed, and provided by an individual possessing legal capacity. Given the frail nature of centenarians, and the prevalence of both sensorial impairments as well as cognitive impairments in this population, we believe that the optimal resolution of this dilemma is through joint consent processes. If EITHER a centenarian or their legally authorized caregiver objects to participation, at any stage of the process, the wishes of the objecting party will be strictly honored. All procedures, instruments, and documents requiring execution have been approved by the University of Georgia Institutional Review Board as well as the Institutional Review Board of each academic institution involved in a given project or core.

Schedule of Participant Testing:

Data collection will begin in month 6 of the Program Project and run through month 48. This is the amount of time required to recruit and test the number of centenarians and control subjects involved in the projects. Each centenarian will be tested by appointment in their own residence. Five two-hour sessions will be required to interview a centenarian completely. All five sessions will be completed within a 30 day interval. In addition, centenarians who have provided consent for brain tissue donation, will be followed longitudinally every 6 months until death with brief neurological exams performed at each follow-up appointment. Younger controls in the 80-89 age range will require approximately 3.5 hours of testing time, which will be scheduled in 2 two-hour sessions. They will also be tested in their own residence by appointment. In addition, 400 controls from 20 to 59 years of age will be tested for Project 1.