The proposed research is aimed at better understanding the neural underpinnings of cognitive reserve (CR). We have postulated that CR mediates the relationship between age- or Alzheimer's disease (AD)-related brain pathology and the clinical impact of that pathology. Our working hypothesis has been that CR operates through individual differences in how tasks are processed in the brain and that we can use fMRI-measured task-related activation to understand these processing differences. In both young and old, we have indentified individual differences in the efficiency and capacity of brain networks elicited by task performance, and have noted that these individual differences are often related to measured CR. We have also identified situations where older adults use different compensatory neural patterns. We now propose to assess how these possible neural implementations of CR are expressed in the presence of quantifiable measures of age- and AD-related brain changes and pathology. These will include MR measures of brain volume, cortical thickness, white matter hyperintensities, resting cerebral blood flow and default network integrity, as well quantified amyloid burden from 18F-AV-45 PET. These measures will be obtained for 50 young and 150 older healthy participants who will also perform two tasks while being imaged with fMRI. This will allow us to explore the neural implementation of CR and determine how CR maintains performance in the presence of brain changes and pathology. We also propose to follow our elder participants over time to determine whether differential expression of these CR networks in healthy elders is associated with reduced risk of important clinical outcomes including cognitive decline and developing mild cognitive impairment (MCI) or AD. This work will lead to better understanding of how aging and AD pathology impacts on the neural systems that mediate cognitive function and the neural mechanisms that differentiate successful and unsuccessful aging. In turn, it may provide clues for remediating or preventing age-related cognitive changes and delaying the onset of AD.

Public Health Relevance

This work will lead to better understanding of how aging and AD pathology impacts on the neural systems that mediate cognitive function and the neural mechanisms that differentiate successful and unsuccessful aging. In turn, it may provide clues for remediating or preventing age-related cognitive changes and delaying the onset of AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG026158-07
Application #
8323907
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Wagster, Molly V
Project Start
2004-09-15
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
7
Fiscal Year
2012
Total Cost
$712,312
Indirect Cost
$267,117
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Oh, Hwamee; Steffener, Jason; Razlighi, Qolamreza R et al. (2016) β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly. J Neurosci 36:1962-70
Gazes, Yunglin; Bowman, F DuBois; Razlighi, Qolamreza R et al. (2016) White matter tract covariance patterns predict age-declining cognitive abilities. Neuroimage 125:53-60
Eich, Teal S; Parker, David; Liu, Dan et al. (2016) Functional brain and age-related changes associated with congruency in task switching. Neuropsychologia 91:211-221
Steffener, Jason; Habeck, Christian; O'Shea, Deirdre et al. (2016) Differences between chronological and brain age are related to education and self-reported physical activity. Neurobiol Aging 40:138-44
Steffener, Jason; Gazes, Yunglin; Habeck, Christian et al. (2016) The Indirect Effect of Age Group on Switch Costs via Gray Matter Volume and Task-Related Brain Activity. Front Aging Neurosci 8:162
Oh, Hwamee; Steffener, Jason; Razlighi, Qolamreza R et al. (2015) Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly. Neurobiol Aging 36:3247-54
Zahodne, Laura B; Manly, Jennifer J; Brickman, Adam M et al. (2015) Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application. Neuropsychologia 77:260-6
Zahodne, Laura B; Stern, Yaakov; Manly, Jennifer J (2015) Differing effects of education on cognitive decline in diverse elders with low versus high educational attainment. Neuropsychology 29:649-57
Gazes, Yunglin; Habeck, Christian; O'Shea, Deirdre et al. (2015) Functional network mediates age-related differences in reaction time: a replication and extension study. Brain Behav 5:e00324
Eich, Teal S; Rakitin, Brian C; Stern, Yaakov (2015) Response-Conflict Moderates the Cognitive Control of Episodic and Contextual Load in Older Adults. J Gerontol B Psychol Sci Soc Sci :

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