@article {309039,
	title = {Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {110},
	year = {2013},
	note = {http://www.pnas.org/content/early/2013/10/30/1313735110.abstract},
	month = {2013 Nov 19},
	pages = {19006-11},
	abstract = {<p>Identification of genes associated with brain aging should markedly improve our understanding of the biological processes that govern normal age-related decline. However, challenges to identifying genes that facilitate successful brain aging are considerable, including a lack of established phenotypes and difficulties in modeling the effects of aging per se, rather than genes that influence the underlying trait. In a large cohort of randomly selected pedigrees (n = 1,129 subjects), we documented profound aging effects from young adulthood to old age (18-83 y) on neurocognitive ability and diffusion-based white-matter measures. Despite significant phenotypic correlation between white-matter integrity and tests of processing speed, working memory, declarative memory, and intelligence, no evidence for pleiotropy between these classes of phenotypes was observed. Applying an advanced quantitative gene-by-environment interaction analysis where age is treated as an environmental factor, we demonstrate a heritable basis for neurocognitive deterioration as a function of age. Furthermore, by decomposing gene-by-aging (G {\texttimes} A) interactions, we infer that different genes influence some neurocognitive traits as a function of age, whereas other neurocognitive traits are influenced by the same genes, but to differential levels, from young adulthood to old age. In contrast, increasing white-matter incoherence with age appears to be nongenetic. These results clearly demonstrate that traits sensitive to the genetic influences on brain aging can be identified, a critical first step in delineating the biological mechanisms of successful aging.</p>},
	keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Aging, Analysis of Variance, Anisotropy, Brain, Cognition, Diffusion tensor imaging, Humans, Memory disorders, Mexican Americans, Middle Aged, Nerve Fibers, Myelinated, Neuroimaging, Pedigree},
	issn = {1091-6490},
	doi = {10.1073/pnas.1313735110},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24191011},
	author = {Glahn, David C and Kent, Jack W and Sprooten, Emma and Diego, Vincent P and Winkler, Anderson M and Curran, Joanne E and McKay, D Reese and Knowles, Emma E and Carless, Melanie A and G{\"o}ring, Harald H H and Dyer, Thomas D and Olvera, Rene L and Fox, Peter T and Almasy, Laura and Charlesworth, Jac and Kochunov, Peter and Duggirala, Ravi and Blangero, John}
}
