Older adults experience disrupted sleep, with reductions in non-rapid eye movement (NREM) slow-wave sleep (SWS) being most prominent. In parallel with alterations of sleep is the cognitive hallmark of aging;a progressive impairment in the ability to form and retain new episodic memories. Within the last ten years, an established literature now suggests that sleep, particularly SWS, is critical for supporting the learning and retention of new episodic memories. Nevertheless, the relationship between age-related alterations of sleep and cognitive memory decline in later life remains poorly understand. The accumulation of central 2- amyloid in later life represents a potential link between these two factors of sleep and memory. Specifically, cortical build-up of 2-amyloid predicts episodic memory decline in healthy aging and Alzheimer's disease. Further, cortical regions associated with the greatest accumulation of 2-amyloid overlap with the cortical regions known to generate SWS. Moreover, it has been demonstrated that brain concentrations of 2- amyloid are tightly coupled to the sleep-wake cycle, and that sleep loss results in an increased presence of 2-amyloid plaques. If correct, this relationship between SWS and 2-amyloid would represent an important, but as yet uncharacterized, feature of cognitive aging, representing a novel treatment target using already existing methods known to enhance SWS. Combining in vivo brain imaging of 2-amyloid (PIB-PET) with high-density EEG measures of sleep and next day brain imaging (fMRI) of episodic learning, this proposal aims to characterize the relationship between 2-amyloid and sleep, and will examine their combined effects on brain function and episodic learning ability.

Public Health Relevance

Combining in vivo brain imaging of 2-amyloid (PIB-PET) with high-density EEG measures of sleep and next day brain imaging (fMRI) of episodic learning, this proposal aims to characterize the relationship between altered sleep, impaired memory, and 2-amyloid brain pathology in later life. These studies examine a novel pathway by which healthy aging may be promoted, affording substantive clinical, societal and public health advantages for older adult populations.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AG039170-03
Application #
8389572
Study Section
Special Emphasis Panel (ZRG1-F12A-E (20))
Program Officer
Hsiao, John
Project Start
2010-12-01
Project End
2013-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
3
Fiscal Year
2013
Total Cost
$55,670
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
Helfrich, Randolph F; Mander, Bryce A; Jagust, William J et al. (2018) Old Brains Come Uncoupled in Sleep: Slow Wave-Spindle Synchrony, Brain Atrophy, and Forgetting. Neuron 97:221-230.e4
Mander, Bryce A; Zhu, Alyssa H; Lindquist, John R et al. (2017) White Matter Structure in Older Adults Moderates the Benefit of Sleep Spindles on Motor Memory Consolidation. J Neurosci 37:11675-11687
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 39:552-566
Mander, Bryce A; Marks, Shawn M; Vogel, Jacob W et al. (2015) ?-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat Neurosci 18:1051-7
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
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
Mander, Bryce A; Santhanam, Sangeetha; Saletin, Jared M et al. (2011) Wake deterioration and sleep restoration of human learning. Curr Biol 21:R183-4