The Vietnam Era Twin Study of Aging (VETSA) study provides a unique opportunity to examine genetic and environmental influences on early cognitive change and associated risk factors. In VETSA 2, we propose our first 5-6 year follow-up of a large, age-homogenous sample that was middle-aged (50s) at baseline. Longitudinal studies of cognitive aging have employed cohort-sequential designs with age-heterogeneous samples that are usually weighted toward older subjects. There is solid evidence of change in midlife to early old age, but because mean change does tend to be modest, increased ability to examine individual differences is key. While no single design can provide all the answers, our novel design does enhance the ability to study differences in within-individual change patterns. By focusing on midlife, our design also has increased potential to identify early predictors of cognitive decline. Moreover, we are including an objective measure of allocation of cognitive effort that will be an important indicator, even in the absence of performance changes. We will follow 720 middle-aged twin pairs (1440 individuals) 5-6 years after collection of baseline neurocognitive, biomedical, and psychosocial data. Mean age at our VETSA 2 follow-up will be 60 (57-66). Applications from 2 Principal Investigators (Kremen, UCSD;Lyons, Boston Univ.) comprise a single integrated project. Our focus is to characterize genetic and environmental influences on early age-related changes in cognitive effort and performance (Aims 1, 2), and to examine major factors that mediate or moderate those changes: APOE [Aim 3];other biomedical risks [Aim 4];lifestyle/psychosocial factors [Aim 5]).
Aims are: 1) Characterize genetic and environmental influences on cognitive change over time (and specific component processes driving change);2) Investigate cognitive efficiency (i.e., ratio of performance to effortful resource allocation [based on task-evoked pupillary responses]) as a key cognitive aging process;3) Examine the relationship of APOE genotype to changes in cognitive function over time;4) Elucidate biomedical risk factors related to cognition and identify specific health risk factors that best predict cognitive aging (with multivariate genetic models not previously used);5) Examine lifestyle and psychosocial factors related to cognitive aging. We will obtain comprehensive assessments in multiple domains, utilize a novel approach that integrates the twin method with experimental/neuroscience approaches of parsing cognitive component processes, and use a cost-effective psychophysiological method (pupillometry) to measure cognitive effort.

Public Health Relevance

VETSA 2 builds upon the unique resource of VETSA 1 and creates an invaluable resource for the study of change from midlife (an under-studied area) to early old age, and for understanding the interplay of biological and environmental factors that are key early predictors of declining or successful aging. The VETSA 2 project builds upon the unique resource of VETSA 1 and creates an invaluable resource for the study of midlife (an under-studied area) and for understanding the interplay of biological and environmental factors that are key determinants of successful aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG018386-08
Application #
7914241
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Spotts, Erica L
Project Start
2000-07-01
Project End
2013-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
8
Fiscal Year
2010
Total Cost
$1,326,454
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Gustavson, Daniel E; Panizzon, Matthew S; Franz, Carol E et al. (2018) Genetic and environmental architecture of executive functions in midlife. Neuropsychology 32:18-30
Beck, Asad; Franz, Carol E; Xian, Hong et al. (2018) Mediators of the Effect of Childhood Socioeconomic Status on Late Midlife Cognitive Abilities: A Four Decade Longitudinal Study. Innov Aging 2:
Gustavson, Daniel E; Panizzon, Matthew S; Elman, Jeremy A et al. (2018) Genetic and Environmental Influences on Verbal Fluency in Middle Age: A Longitudinal Twin Study. Behav Genet :
Gustavson, Daniel E; Panizzon, Matthew S; Elman, Jeremy A et al. (2018) Stability of genetic and environmental influences on executive functions in midlife. Psychol Aging 33:219-231
Hatton, Sean N; Franz, Carol E; Elman, Jeremy A et al. (2018) Negative fateful life events in midlife and advanced predicted brain aging. Neurobiol Aging 67:1-9
Finkel, Deborah; Franz, Carol E; Christensen, Kaare et al. (2018) Longitudinal Twin Study of Subjective Health: Differences in Genetic and Environmental Components of Variance Across Age and Sex. J Gerontol B Psychol Sci Soc Sci :
McEvoy, Linda K; Fennema-Notestine, Christine; Elman, Jeremy A et al. (2018) Alcohol intake and brain white matter in middle aged men: Microscopic and macroscopic differences. Neuroimage Clin 18:390-398
Rana, Brinda K; Panizzon, Matthew S; Franz, Carol E et al. (2018) Association of Sleep Quality on Memory-Related Executive Functions in Middle Age. J Int Neuropsychol Soc 24:67-76
Breen, Michael S; Tylee, Daniel S; Maihofer, Adam X et al. (2018) PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma. Neuropsychopharmacology 43:469-481
Panizzon, Matthew S; Hauger, Richard L; Xian, Hong et al. (2018) Interactive effects of testosterone and cortisol on hippocampal volume and episodic memory in middle-aged men. Psychoneuroendocrinology 91:115-122

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