Cognitive decline is a problematic and disabling consequence of aging, with memory impairment being one of the most debilitating symptoms. These cognitive changes are paralleled by a dramatic decrease in non-rapid eye movement (NREM) sleep quality, indexed by a reduction in electroencephalographic (EEG) slow wave activity (SWA). Here, we propose that -Amyloid accumulation-a leading candidate underlying cognitive decline both in aging and Alzheimer's disease-is one neuropathological factor contributing to disrupted NREM SWA and impaired memory consolidation in older adults. Specifically, we seek to test the hypothesis that -Amyloid in a set of midline cortical brain regions disrupts the neural generation of NREM SWA-both cross-sectionally, and longitudinally-thereby impairing hippocampal-dependent memory consolidation in the elderly. As such, these experiments will determine whether or not -Amyloid exerts an effect on memory through sleep, and if so, exactly how - Amyloid disrupts NREM sleep physiology, resulting in memory impairment in older adults. Translationally, these experiments may reveal new treatment pathways targeting NREM SWA enhancements that improve memory, thereby moderating the cognitive burden associated with -Amyloid aggregation.

Public Health Relevance

This proposal seeks to determine whether or not -Amyloid exerts a longitudinal effect on memory through an impact on sleep, and if so, exactly how -Amyloid disrupts NREM sleep physiology, resulting in memory impairment in older adults. Translationally, these experiments may reveal new treatment pathways targeting NREM SWA enhancements that improve memory, thereby moderating the cognitive burden associated with -Amyloid aggregation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG031164-07
Application #
9232042
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Mackiewicz, Miroslaw
Project Start
2008-08-01
Project End
2020-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Mander, Bryce A; Winer, Joseph R; Jagust, William J et al. (2016) Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease? Trends Neurosci 39:552-66
Saletin, Jared M; Goldstein-Piekarski, Andrea N; Greer, Stephanie M et al. (2016) Human Hippocampal Structure: A Novel Biomarker Predicting Mnemonic Vulnerability to, and Recovery from, Sleep Deprivation. J Neurosci 36:2355-63
Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Saletin, Jared M et al. (2015) Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat. J Neurosci 35:10135-45
Mander, Bryce A; Marks, Shawn M; Vogel, Jacob W et al. (2015) β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat Neurosci 18:1051-7
Goldstein, Andrea N; Walker, Matthew P (2014) The role of sleep in emotional brain function. Annu Rev Clin Psychol 10:679-708
Mander, Bryce A; Rao, Vikram; Lu, Brandon et al. (2014) Impaired prefrontal sleep spindle regulation of hippocampal-dependent learning in older adults. Cereb Cortex 24:3301-9
Saletin, Jared M; van der Helm, Els; Walker, Matthew P (2013) Structural brain correlates of human sleep oscillations. Neuroimage 83:658-68
Stickgold, Robert; Walker, Matthew P (2013) Sleep-dependent memory triage: evolving generalization through selective processing. Nat Neurosci 16:139-45
Mander, Bryce A; Rao, Vikram; Lu, Brandon et al. (2013) Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat Neurosci 16:357-64
Greer, Stephanie M; Goldstein, Andrea N; Walker, Matthew P (2013) The impact of sleep deprivation on food desire in the human brain. Nat Commun 4:2259

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