Our memory changes as we age. Age-related memory decline in and of itself represents a significant public health impact, but cognitive decline - and in particular memory decline - has been shown to be an important risk factor for Alzheimer's Disease (AD). Examining neurocognitive aging will help us better characterize pathological and non-pathological changes in the brain throughout the lifespan and identify preclinical markers for cognitive decline. This project extends our prior work into the exact nature of age-related memory decline and into its neural bases. Like our prior project, this proposal draws heavily on animal models of aging and computational models of memory to test specific hypotheses about age-related memory decline. In our prior funding period, we focused almost exclusively on the hippocampus, demonstrating age- related disruptions in the hippocampal circuit that parallel those found in the rodent and demonstrating how these changes affect specific kinds of memory. In particular, we showed how the human hippocampal dentate gyrus is critically involved in episodic memory by virtue of its exceptional capacity for performing pattern separation, or the ability to isolate similar memories from each other. We also showed how this circuit is disrupted gradually over the course of aging and how this is linked to age-related loss of the detail or episodic components of a memory. One goal of the project is to build extensively on the behavioral tasks that we have pioneered and that are being widely adopted in the field so that we can develop and neurobiologically validate an entire suite of behavioral tasks that are maximally sensitive to hippocampal function and to age- related cognitive decline. As this loss is not confined to the hippocampus, but includes changes in the adjacent medial temporal lobe cortices and in the prefrontal cortex, we propose to examine in detail changes in these regions and in their interactions with the hippocampus. Here again we draw heavily on neurobiological findings from the rodent to test specific hypotheses about age-related changes in regions like the perirhinal cortex and to assess changes in the functional contributions of and interrelationship between hippocampal and prefrontal age-related changes in memory. Like our prior work, we propose to collect a comprehensive suite of behavioral and neuroimaging data from a large sample of adults. By collecting an extensive set of measures on each participant, we can examine interrelationships that would otherwise be impossible. In addition to our own specific questions and hypotheses, the extensive set of measures (which includes longitudinal assessment of participants from our prior work) will be valuable to other researchers. As before, we will make all components of the data widely available to others.

Public Health Relevance

The percentage of the world's population aged 65 and older is expected to be triple what it was several decades ago and double the current proportion, representing a huge demographic shift. The incidence of dementia (e.g., Alzheimer's Disease, Vascular Dementia, etc.) increases dramatically with age. Outside of dementia, there are also clear cognitive effects of age, particularly in the domain of memory. Understanding the neural mechanisms that underlie these age-related deficits is crucial for understanding the effects of aging and dementia, and paving the way to improve treatments for both normal and pathological changes in memory and for early prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG034613-06
Application #
8786701
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wagster, Molly V
Project Start
2009-09-15
Project End
2019-04-30
Budget Start
2014-09-15
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
City
Irvine
State
CA
Country
United States
Zip Code
92697
Bennett, Ilana J; Stark, Craig E L (2016) Mnemonic discrimination relates to perforant path integrity: An ultra-high resolution diffusion tensor imaging study. Neurobiol Learn Mem 129:107-12
Clemenson, Gregory D; Stark, Craig E L (2015) Virtual Environmental Enrichment through Video Games Improves Hippocampal-Associated Memory. J Neurosci 35:16116-25
Yushkevich, Paul A; Amaral, Robert S C; Augustinack, Jean C et al. (2015) Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: towards a harmonized segmentation protocol. Neuroimage 111:526-41
LePort, Aurora K R; Stark, Shauna M; McGaugh, James L et al. (2015) Highly Superior Autobiographical Memory: Quality and Quantity of Retention Over Time. Front Psychol 6:2017
Stark, Shauna M; Stevenson, Rebecca; Wu, Claudia et al. (2015) Stability of age-related deficits in the mnemonic similarity task across task variations. Behav Neurosci 129:257-68
Bennett, Ilana J; Huffman, Derek J; Stark, Craig E L (2015) Limbic Tract Integrity Contributes to Pattern Separation Performance Across the Lifespan. Cereb Cortex 25:2988-99
Allen, Timothy A; Morris, Andrea M; Stark, Shauna M et al. (2015) Memory for sequences of events impaired in typical aging. Learn Mem 22:138-48
Chang, Allen; Murray, Elizabeth; Yassa, Michael A (2015) Mnemonic discrimination of similar face stimuli and a potential mechanism for the ""other race"" effect. Behav Neurosci 129:666-72
Huffman, Derek J; Stark, Craig E L (2014) Multivariate pattern analysis of the human medial temporal lobe revealed representationally categorical cortex and representationally agnostic hippocampus. Hippocampus 24:1394-403
Reagh, Zachariah M; Roberts, Jared M; Ly, Maria et al. (2014) Spatial discrimination deficits as a function of mnemonic interference in aged adults with and without memory impairment. Hippocampus 24:303-14

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