This project proposes to use structural and functional neuroimaging methods to better understand how the brain changes in healthy aging, and the consequences of those changes on cognitive function. It examines age-related changes in working memory ability - a fundamental capacity that underlies many complex cognitive behaviors, and that declines with age. The central hypothesis of this study is that working memory ability arises from coherent neural oscillatory activity in a network of brain regions, and that age-related declines in working memory ability reflect the breakdown of coherent neural activity in this network due to age-related changes in white matter structure. To test this hypothesis, high temporal resolution methods of electro- and magnetoencephalography (EEC and MEG) will be integrated with the high spatial resolution method of functional magnetic resonance imaging (MRI) to characterize the dynamic spatiotemporal patterns of brain activity that underlie working memory ability in young adults, and to determine how healthy aging affects these patterns. Diffusion tensor imaging (DTI) will be used to assess white matter microstructural integrity, and age-related reductions in coherent activity between distributed neural regions will be related to age-related reductions in white matter integrity. It is hypothesized that age-related changes in frontal white matter disrupts the coherent activity in frontal-parietal networks necessary for working memory task performance, and that the reduction in frontal white matter integrity contributes to age-related reductions in regional frontal cortical thickness. To achieve these research goals, the candidate, who has a strong background in MEG and EEC research, seeks training through formal coursework and interaction with her sponsors in structural and functional MRI acquisition and analyses, multimodal integration of MEG/EEG and MRI data, cortical reconstruction, parcellation, and quantification, and DTI acquisition and analyses. Her sponsors, leaders in the field of neuroimaging and multimodal analyses, and the supportive and resource- rich environment of UCSD, will ensure the candidate's mastery of these new techniques. Relevance: This project will further understanding of the structural and functional changes in the brain that occur as part of normal aging, and that underlie age-related changes in cognitive ability. This knowledge will provide a basis for better understanding of pathological brain changes that occur in age-related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG029218-05
Application #
8127793
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Wagster, Molly V
Project Start
2007-09-30
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2011
Total Cost
$116,470
Indirect Cost
Name
University of California San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Desikan, R S; Schork, A J; Wang, Y et al. (2015) Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. Mol Psychiatry 20:1588-95
Oania, Rafael; McEvoy, Linda K (2015) Plasma leptin levels are not predictive of dementia in patients with mild cognitive impairment. Age Ageing 44:53-8
Desikan, Rahul S; Thompson, Wesley K; Holland, Dominic et al. (2014) The role of clusterin in amyloid-?-associated neurodegeneration. JAMA Neurol 71:180-7
Fjell, Anders M; McEvoy, Linda; Holland, Dominic et al. (2014) What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus. Prog Neurobiol 117:20-40
Chang, Yu-Ling; Fennema-Notestine, Christine; Holland, Dominic et al. (2014) APOE interacts with age to modify rate of decline in cognitive and brain changes in Alzheimer's disease. Alzheimers Dement 10:336-48
Fjell, Anders M; McEvoy, Linda; Holland, Dominic et al. (2013) Brain changes in older adults at very low risk for Alzheimer's disease. J Neurosci 33:8237-42
Holland, D; Desikan, R S; Dale, A M et al. (2013) Higher rates of decline for women and apolipoprotein E epsilon4 carriers. AJNR Am J Neuroradiol 34:2287-93
Desikan, Rahul S; Thompson, Wesley K; Holland, Dominic et al. (2013) Heart fatty acid binding protein and A?-associated Alzheimer's neurodegeneration. Mol Neurodegener 8:39
Desikan, R S; McEvoy, L K; Holland, D et al. (2013) Apolipoprotein E epsilon4 does not modulate amyloid-?-associated neurodegeneration in preclinical Alzheimer disease. AJNR Am J Neuroradiol 34:505-10
McEvoy, Linda K; Kritz-Silverstein, Donna; Barrett-Connor, Elizabeth et al. (2013) Changes in alcohol intake and their relationship with health status over a 24-year follow-up period in community-dwelling older adults. J Am Geriatr Soc 61:1303-8

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