2005 — 2007 |
Mander, Bryce A. |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
The Neural Response to Sleep Loss in the Elderly @ Northwestern University
DESCRIPTION (provided by applicant): In the proposed study, our primary goal is to determine if older adults, as compared to younger adults, will be less able to recruit neural areas necessary for compensation during sleep deprivation on an attention task and a task of response inhibition. Tasks of visual spatial attention and response inhibition will be used, because they assess the functioning of two distinct networks particularly vulnerable to sleep loss. We specifically propose to use functional magnetic resonance imaging (fMRI) to investigate the effects of 36 hours of sleep deprivation on the neural response to both a visual spatial attention task and a task of response inhibition. Functional magnetic resonance imaging (fMRI) will be used to measure blood flow changes via the blood oxygen level dependent (BOLD) method. This method allows for the high spatial and temporal resolution necessary for these proposed investigations. Influence of age and task type will be examined to determine how sleep loss interacts with each of these factors to produce altered neural function and impaired performance.
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0.942 |
2010 — 2013 |
Mander, Bryce A. |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Aging, Sleep, and Beta-Amyloid Pathology and Their Impact On Memory @ University of California Berkeley
DESCRIPTION (provided by applicant): 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.
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1 |
2020 — 2021 |
Mander, Bryce A. |
K01Activity Code Description: For support of a scientist, committed to research, in need of both advanced research training and additional experience. |
Relationships Between Local and Global Mechanisms of Sleep Apnea, Alzheimer's Disease Biomarkers, and Memory Impairment in Cognitively Asymptomatic Older Adults @ University of California-Irvine
Project Summary/Abstract Epidemiologic evidence has established obstructive sleep apnea (OSA) as a risk factor for Alzheimer?s disease (AD). However, the mechanisms of this increase in AD risk remain unclear. Three potentially AD-relevant clinical features of OSA include severity of hypoxemia, global sleep fragmentation, and local deficits in memory-relevant sleep oscillations, i.e. slow waves and sleep spindles. These clinical features of OSA have been independently linked to amyloid and tau burden and accumulation, medial temporal lobe (MTL) degeneration, and MTL- dependent memory impairment?all hallmark biomarkers of AD. However, it remains unclear how each of these features relate to AD pathophysiology or MTL-dependent memory decline in patients with OSA. The overarching research objective of this proposal is to address these unknowns. The proposed specific aims are to determine whether distinct global and local OSA features are associated with 1) cortical amyloid burden, 2) MTL tau burden, and 3) degeneration of specific MTL brain circuits supporting multiple forms of memory known to depend on sleep and be vulnerable to AD pathophysiology. The proposed aims will be supported by leveraging existing resources, and collecting high density electroencephalography (hdEEG, 256 channels) sleep recordings in cognitively normal older adults (60-85 years) undergoing positron emission tomography (PET) to assess amyloid and tau burden, as well as ultrahigh resolution magnetic resonance imaging (uhr-MRI) of MTL structure. The proposed study will therefore capitalize on an opportunity to examine how OSA relates to AD pathological burden, MTL structure and function, and memory in an unprecedented level of detail and breadth. This is congruent with both my short and long-term career goals. Specifically, I plan to generate research proposals seeking funding to uncover the impact of distinct forms of sleep disturbance on circuit and molecular mechanisms of AD pathogenesis in humans. This will support my efforts to establish a clinical research program evaluating i) the contribution of sleep disturbance to the onset and progression of various forms of neurodegenerative disease across clinical stages, ii) the utility of sleep-based biomarkers to predict dementia onset and aid differential diagnosis between dementias, and iii) the utility of targeted sleep-based interventions to arrest cognitive decline associated with AD and related dementias. This research proposal and my long-term career goals are supported by my training plan overseen by my mentoring team which includes experts in hdEEG, uhr-MRI, MTL-dependent memory circuit function, PET methods in the context of aging and AD?including amyloid and tau PET, clinical aspects of sleep disorders, geriatric psychiatry, and neurodegenerative disease, and clinical trial design and implementation in the context of sleep disorders and AD. The proposed training plan includes structured mentoring on each of these topics and participation in a clinical research certificate program, as well as a course focused on clinical trials in AD. By establishing this research program, I hope to develop sleep-based approaches to reduce risk, delay onset, and slow progression of dementia and age-related cognitive decline.
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0.981 |