The proposed study will consider models and methods to examine the genetic and environmental influences on cognitive decline trajectories, including both estimates of total genetic influence and tests of the effects of specific genes. Because dementia may represent one extreme of cognitive changes seen with advancing age, methods are used that simultaneously consider normal aging and dementia and uncover tandem influences on both normative cognitive change and those effects specific to dementia. Cognitive measures from a unique population based sample of 788 same-sex twins from the Swedish/Adoption Twin Study of Aging and the Study of Dementia in Swedish Twins will be utilized; domain areas will include crystallized and fluid abilities, perceptual speed and memory. Cognitive decline trajectories will be estimated using longitudinal growth models where rate of change is quantified for each subjects' longitudinal profile of cognitive scores. We will examine the association of health traits, psychosocial traits, and measured susceptibility genotypes (e.g., APOE, LRP, HLA, other emerging loci) with cognitive decline trajectories, making use of current association and linkage methods utilized in twin and sib-pairs. Of principal interest are: (1) What amount of variation in cognitive decline trajectories is explained by significant risk genotypes? (2) What amount of variation in decline trajectories is explained by complex physical and psychosocial factors (e.g., educational attainment, serum lipoprotein levels, pulmonary function, smoking, head injury, self-efficacy)? Among significant factors, what are the shared genetic and environmental sources of covariance? (3) Are genotype-environment interactions present? For example, do identical (MZ) twins positive for environmental exposures (e.g., head injury) show greater decline than their co-twins without the environmental exposure? Is the interaction dependent on risk allele status (e.g., APOE 4)? The examination specific genetic and environmental influences on cognitive decline will lead to an increased understanding of factors that contribute to cognitive changes in late-life.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
7R01AG017561-03
Application #
6408584
Study Section
Special Emphasis Panel (ZRG1-SNEM-2 (01))
Program Officer
Wagster, Molly V
Project Start
1999-09-30
Project End
2004-03-31
Budget Start
2001-02-15
Budget End
2004-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$45,558
Indirect Cost
Name
University of California Riverside
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Riverside
State
CA
Country
United States
Zip Code
92521
Reynolds, Chandra A; Gatz, Margaret; Prince, Jonathan A et al. (2010) Serum lipid levels and cognitive change in late life. J Am Geriatr Soc 58:501-9
Reynolds, Chandra A; Gatz, Margaret; Berg, Stig et al. (2007) Genotype-environment interactions: cognitive aging and social factors. Twin Res Hum Genet 10:241-54
Reynolds, Chandra A; Jansson, Marten; Gatz, Margaret et al. (2006) Longitudinal change in memory performance associated with HTR2A polymorphism. Neurobiol Aging 27:150-4
Reynolds, Chandra A; Prince, Jonathan A; Feuk, Lars et al. (2006) Longitudinal memory performance during normal aging: twin association models of APOE and other Alzheimer candidate genes. Behav Genet 36:185-94
Finkel, Deborah; Reynolds, Chandra A; McArdle, John J et al. (2005) The longitudinal relationship between processing speed and cognitive ability: genetic and environmental influences. Behav Genet 35:535-49
Reynolds, Chandra A; Finkel, Deborah; McArdle, John J et al. (2005) Quantitative genetic analysis of latent growth curve models of cognitive abilities in adulthood. Dev Psychol 41:3-16
Finkel, Deborah; Pedersen, Nancy L; Reynolds, Chandra A et al. (2003) Genetic and environmental influences on decline in biobehavioral markers of aging. Behav Genet 33:107-23
Pedersen, Nancy L; Ripatti, Samuli; Berg, Stig et al. (2003) The influence of mortality on twin models of change: addressing missingness through multiple imputation. Behav Genet 33:161-9
Finkel, Deborah; Reynolds, Chandra A; McArdle, John J et al. (2003) Latent growth curve analyses of accelerating decline in cognitive abilities in late adulthood. Dev Psychol 39:535-50
Reynolds, Chandra A; Finkel, Deborah; Gatz, Margaret et al. (2002) Sources of influence on rate of cognitive change over time in Swedish twins: an application of latent growth models. Exp Aging Res 28:407-33

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