Whereas dementia and stroke affect only fraction of the population, there is a type of brain dysfunction that will affect all of us if we live long enough: normal aging. As we age, the anatomical and functional integrity of our brain declines, and so do our cognitive abilities. Even if relatively mild, this decline affects a large number of people, and hence, it has a great impact at the population level. The development of any rational remedial approach depends on a clear understanding of the effects of healthy aging on the neural basis of cognition. Moreover, this knowledge is critical for research on the devastating effects of Alzheimer's Disease. The proposed research will contribute to this knowledge by directly linking age-related deficits in cognitive abilities to age-related deficits in brain anatomy and function. The approach integrates 3 methodological approaches that have been seldom combined in the past. First, we will use functional MRI (fMRI) to brain activity that changes as a function of aging. We expect to find not age-related decreases in activity signaling deficit cognitive processing, but also age-related increases in activity signaling compensatory mechanisms in the aging brain. Second, we will use diffusion tensor imaging (DTI) to measure the effects of aging on white-matter integrity, as there is evidence that aging impairs not only individual brain regions but also the connections between them. Finally, we will use a comprehensive batter of standardized tests to identify individual differences in neuropsychological status within the aging population. One of the cognitive functions most affected by healthy (and pathological) aging is episodic memory, which refers to memory for personally experienced past events. We propose six fMRI studies to investigate the effects of aging on brain activity associated with acquiring episodic information (encoding). Two brain regions are particularly important for encoding: the prefrontal cortex and the medial temporal lobes. We will measure activity in these regions, and their interactions, while young and older participants learn new episodic information in the scanner. In particular, we will investigate two critical factors accounting for age-related deficits in encoding (1) Reduced cognitive resources. To investigate this factor, we will divide attention and vary the speed of stimuli presentation during encoding. (2) Impaired binding processes. To investigate this factor we will compare memory for items vs. memory for semantic or perceptual associations. Finally, we will investigate the interactions between these two factors.

Public Health Relevance

The results of the proposed studies will clarify the neural correlates of age-related deficits in episodic encoding, and will have important implications for the promotion of health. They will help develop cognitive training methods and will provide an essential baseline for research on Alzheimer's Disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG019731-09
Application #
8113236
Study Section
Cognition and Perception Study Section (CP)
Program Officer
Wagster, Molly V
Project Start
2001-09-01
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
9
Fiscal Year
2011
Total Cost
$303,205
Indirect Cost
Name
Duke University
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Moscovitch, Morris; Cabeza, Roberto; Winocur, Gordon et al. (2016) Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation. Annu Rev Psychol 67:105-34
Davis, Simon W; Cabeza, Roberto (2015) Cross-hemispheric collaboration and segregation associated with task difficulty as revealed by structural and functional connectivity. J Neurosci 35:8191-200
Wang, Wei-Chun; Dew, Ilana T Z; Cabeza, Roberto (2015) Age-related differences in medial temporal lobe involvement during conceptual fluency. Brain Res 1612:48-58
Wing, Erik A; Ritchey, Maureen; Cabeza, Roberto (2015) Reinstatement of individual past events revealed by the similarity of distributed activation patterns during encoding and retrieval. J Cogn Neurosci 27:679-91
Daselaar, Sander M; Iyengar, Vijeth; Davis, Simon W et al. (2015) Less wiring, more firing: low-performing older adults compensate for impaired white matter with greater neural activity. Cereb Cortex 25:983-90

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