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.
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