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Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2024)

Alzheimer’s disease is a progressive form of dementia with no effective treatments. Episodic memory deficits are a defining cognitive symptom of Alzheimer’s disease, which may be related to changes in the medial temporal lobes (MTL). The MTL facilitates episodic memory function and is particularly vulnerable to Alzheimer’s disease pathology. Both sleep and physical activity are linked to episodic memory function, including pattern separation operations reliant on the MTL. Evidence in young adults suggests that sleep and exercise are each independently linked to mnemonic discrimination (behavioral correlate of pattern separation), but it is unclear whether they interact to do so, and through what mechanisms. Whether these relationships are altered in older adults at-risk for Alzheimer’s disease is also unknown. To fill this knowledge gap, a series of studies were conducted. In Chapter 2, self-report measurements of sleep, physical activity, and cognitive function were used to statistically model the mediating effect of sleep in the physical activity-cognition relationship. In Chapters 3 and 4, high-density electroencephalography was recorded during overnight sleep to measure the expression and coupling of non-rapid eye movement (NREM) sleep oscillations, a memory task assessing mnemonic discrimination was administered prior to and following sleep to measure sleep-dependent memory consolidation, and questionnaire data assessing physical activity frequency and duration was collected from 36 older adults. High-resolution resting-state functional magnetic resonance imaging data previously collected from this same participant cohort was analyzed to derive measures of resting-state network modularity and MTL centrality. Chapters 3 and 4 addressed three specific aims: (1) whether local expression and coupling of NREM sleep oscillations are associated with sleep-dependent memory consolidation (Chapter 3), (2) whether network modularity and measures of MTL centrality are associated with sleep-dependent memory consolidation (Chapter 3), and (3) whether physical activity is associated with these same mechanisms (Chapter 4). This research provides novel insights into the neurobiological mechanisms supporting the relationships among sleep, physical activity, and memory consolidation in older adults. Findings from this dissertation could guide prospective physical activity and sleep-based interventional studies to improve memory function and inform public health recommendations to reduce Alzheimer’s disease risk by underscoring the importance of sleep.

    Creative Commons 'BY-NC-ND' version 4.0 license
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2022)

    Study objectives

    To determine whether subjective measures of exercise and sleep are associated with cognitive complaints and whether exercise effects are mediated by sleep.

    Methods

    This study analyzed questionnaire data from adults (18-89) enrolled in a recruitment registry. The Cognitive Function Instrument (CFI) assessed cognitive complaints. Medical Outcomes Study Sleep Scale (MOS-SS) subscales and factor scores assessed sleep quality, daytime sleepiness, nighttime disturbance, and insomnia and obstructive sleep apnea (OSA)-like symptoms. Exercise frequency was defined as the weekly number of exercise sessions. Exercise frequency, MOS-SS subscales, and factor scores were examined as predictors of CFI score, adjusting for age, body mass index, education, sex, cancer diagnosis, antidepressant usage, psychiatric conditions, and medical comorbidities. Analyses of covariance examined the relationship between sleep duration groups (short, mid-range, and long) and CFI score, adjusting for covariates. Mediation by sleep in the exercise-CFI score relationship was tested.

    Results

    Data from 2106 adults were analyzed. Exercise and MOS-SS subscales and factor scores were associated with CFI score. Higher Sleep Adequacy scores were associated with fewer cognitive complaints, whereas higher Sleep Somnolence, Sleep Disturbance, Sleep Problems Index I, Sleep Problems Index II, and factor scores were associated with more cognitive complaints. MOS-SS subscales and factor scores, except Sleep Disturbance and the insomnia factor score, mediated the association between exercise and cognitive complaints.

    Conclusions

    The relationship between exercise frequency and subjective cognitive performance is mediated by sleep. In particular, the mediation effect appears to be driven by symptoms possibly suggestive of OSA which are negatively associated with exercise engagement, sleep quality, daytime sleepiness, and subjective cognitive performance.
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2023)
      Older adults may harbor large amounts of amyloid-β (Aβ) pathology, yet still perform at age-normal levels on memory assessments. We tested whether functional brain networks confer resilience or compensatory mechanisms to support memory in the face of Aβ pathology. Sixty-five cognitively normal older adults received high-resolution resting state fMRI to assess functional networks, 18F-florbetapir-PET to measure Aβ, and a memory assessment. We characterized functional networks with graph metrics of local efficiency (information transfer), modularity (specialization of functional modules), and small worldness (balance of integration and segregation). There was no difference in functional network measures between older adults with high Aβ (Aβ+) compared to those with no/low Aβ (Aβ-). However, in Aβ+ older adults, increased local efficiency, modularity, and small worldness were associated with better memory performance, while this relationship did not occur Aβ- older adults. Further, the association between increased local efficiency and better memory performance in Aβ+ older adults was localized to local efficiency of the default mode network and hippocampus, regions vulnerable to Aβ and involved in memory processing. Our results suggest functional networks with modular and efficient structures are associated with resilience to Aβ pathology, providing a functional target for intervention.
        Cover page: Functional network structure supports resilience to memory deficits in cognitively normal older adults with amyloid-β pathology
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2021)

        Study objectives

        Aerobic fitness (AF) and sleep are major determinants of health in adolescents and impact neurocognitive and psychological development. However, little is known about the interactions between AF and sleep during the developmental transition experienced across adolescence. This study aimed to consider the relationships between AF and habitual sleep patterns and sleep neurophysiology in healthy adolescents.

        Methods

        Subjects (mean age = 14.6 ± 2.3 years old, range 11-17, 11 females) were evaluated for AF (peak VO2 assessed by ramp-type progressive cycle ergometry in the laboratory), habitual sleep duration and efficiency (7-14 days actigraphy), and topographic patterns of spectral power in slow wave, theta, and sleep spindle frequencies in non-rapid eye movement (NREM) sleep using overnight polysomnography (PSG) with high-density electroencephalography (hdEEG, 128 channels).

        Results

        Significant relationships were observed between peak VO2 and habitual bedtime (r = -0.650, p = .009) and wake-up time (r = -0.603, p = .017), with greater fitness associated with going to bed and waking up earlier. Peak VO2 significantly predicted slow oscillations (0.5-1 Hz, p = .018) and theta activity (4.5-7.5 Hz, p = .002) over anterior frontal and central derivations (p < .001 and p = .001, respectively) after adjusting for sex and pubertal development stage. Similar associations were detected for fast sleep spindle activity (13-16 Hz, p = .006), which was greater over temporo-parietal derivations.

        Conclusions

        Greater AF was associated with a more mature pattern of topographically-specific features of sleep EEG known to support neuroplasticity and cognitive processes and which are dependent on prefrontal cortex and hippocampal function in adolescents and adults. AF was also correlated with a smaller behavioral sleep phase delay commonly seen during adolescence.
          Cover page: Aerobic fitness and the sleeping brain of adolescents—a pilot study
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2023)
          Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aβ) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs. Current methods for detecting AD pathology, however, are often expensive and invasive, limiting wide and easy access to a clinical setting. A non-invasive, cost-efficient platform, such as computerized cognitive tests, could be potentially useful to identify at-risk individuals as early as possible. In this study, we examined the diagnostic value of an episodic memory task, the mnemonic discrimination task (MDT), for predicting risk of cognitive impairment or Aβ burden. We constructed a random forest classification algorithm, utilizing MDT performance metrics and various neuropsychological test scores as input features, and assessed model performance using area under the curve (AUC). Models based on MDT performance metrics achieved classification results with an AUC of 0.83 for cognitive status and an AUC of 0.64 for Aβ status. Our findings suggest that mnemonic discrimination function may be a useful predictor of progression to prodromal AD or increased risk of Aβ load, which could be a cost-efficient, noninvasive cognitive testing solution for potentially wide-scale assessment of AD pathological and cognitive risk.
            Cover page: Examining the diagnostic value of the mnemonic discrimination task for classification of cognitive status and amyloid-beta burden
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2022)

            Study objectives

            Fast frequency sleep spindles are reduced in aging and Alzheimer's disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD.

            Methods

            Fifty-eight cognitively unimpaired, β-amyloid-negative, older adults (mean ± SD; 61.4 ± 6.3 years, 38 female) enriched with parental history of AD (77.6%) and apolipoprotein E (APOE) ε4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, β-amyloid and tau proteins, and neurodegeneration were combined with polysomnography (PSG) using high-density electroencephalography and assessment of overnight memory retention. Parallelized serial mediation models were used to assess indirect effects of age on fast frequency (13 to <16Hz) sleep spindle measures through these AD biomarkers.

            Results

            Glial activation was associated with prefrontal fast frequency sleep spindle expression deficits. While adjusting for sex, APOE ε4 genotype, apnea-hypopnea index, and time between CSF sampling and sleep study, serial mediation models detected indirect effects of age on fast sleep spindle expression through microglial activation markers and then tau phosphorylation and synaptic degeneration markers. Sleep spindle expression at these electrodes was also associated with overnight memory retention in multiple regression models adjusting for covariates.

            Conclusions

            These findings point toward microglia dysfunction as associated with tau phosphorylation, synaptic loss, sleep spindle deficits, and memory impairment even prior to β-amyloid positivity, thus offering a promising candidate therapeutic target to arrest cognitive decline associated with aging and AD.
              Cover page: Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity.
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