The proposed research is aimed at better understanding the neural underpinnings of cognitive reserve (CR). We have postulated that CR moderates the relationship between age- or Alzheimer?s disease (AD)-related brain pathology and the clinical impact of that pathology. Our findings suggest 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. We have also begun to look at the factors influencing brain integrity, or brain reserve (BR). The promise of better understanding CR and BR is that these concepts have implications for preservation of function over time, so the neural mechanisms underlying reserve are optimally studied in a longitudinal context. We propose to initiate longitudinal follow-up at 5 years of a large, well characterized, initially healthy group of young (n=50) and older (N=150) adults, in order to elucidate the neural mechanism underlying CR that help maintain BR and successful cognitive performance in the face of advancing age-related brain changes and AD pathology. These participants have already been studied at baseline with two fMRI tasks, as well as quantified measures of age- and AD-related brain changes and pathology, including MR measures of brain volume, cortical thickness, white matter hyperintensities, resting cerebral blood flow and default network integrity, as well quantified amyloid burden from Florbetaben PET. We have already identified candidate neural mechanisms for CR. We will 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. We will also explore how measured CR and CR networks maintain BR and how they moderate the effect of observed brain changes and advancing AD pathology in order to preserve cognitive functioning.

Public Health Relevance

Impact This work will lead to better understanding of how age-related brain changes and advancing AD pathology impact on the neural systems that mediate cognitive function and elucidate the neural mechanisms that differentiate successful from unsuccessful aging. In turn, it should 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 #
5R01AG026158-12
Application #
9471759
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Wagster, Molly V
Project Start
2017-05-01
Project End
2022-03-31
Budget Start
2018-05-01
Budget End
2019-03-31
Support Year
12
Fiscal Year
2018
Total Cost
Indirect Cost
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; Razlighi, Qolamreza R; Stern, Yaakov (2018) Multiple pathways of reserve simultaneously present in cognitively normal older adults. Neurology 90:e197-e205
Eich, Teal S; MacKay-Brandt, Anna; Stern, Yaakov et al. (2018) Age-Based Differences in Task Switching Are Moderated by Executive Control Demands. J Gerontol B Psychol Sci Soc Sci 73:954-963
Eich, Teal S; Gonçalves, Beatriz M M; Nee, Derek E et al. (2018) Inhibitory Selection Mechanisms in Clinically Healthy Older and Younger Adults. J Gerontol B Psychol Sci Soc Sci 73:612-621
Li, Peipei; Tsapanou, Angeliki; Qolamreza, Razlighi R et al. (2018) White matter integrity mediates decline in age-related inhibitory control. Behav Brain Res 339:249-254
Eich, Teal S; Razlighi, Qolamreza R; Stern, Yaakov (2017) Perceptual and memory inhibition deficits in clinically healthy older adults are associated with region-specific, doubly dissociable patterns of cortical thinning. Behav Neurosci 131:220-5
Grinband, Jack; Steffener, Jason; Razlighi, Qolamreza R et al. (2017) BOLD neurovascular coupling does not change significantly with normal aging. Hum Brain Mapp :
Razlighi, Qolamreza R; Oh, Hwamee; Habeck, Christian et al. (2017) Dynamic Patterns of Brain Structure-Behavior Correlation Across the Lifespan. Cereb Cortex 27:3586-3599
Leavitt, Victoria M; Buyukturkoglu, Korhan; Inglese, Matilde et al. (2017) Protective personality traits: High openness and low neuroticism linked to better memory in multiple sclerosis. Mult Scler 23:1786-1790
Parker, David; Liu, Xueqing; Razlighi, Qolamreza R (2017) Optimal slice timing correction and its interaction with fMRI parameters and artifacts. Med Image Anal 35:434-445
Stern, Yaakov (2017) An approach to studying the neural correlates of reserve. Brain Imaging Behav 11:410-416

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