Brandon Lu

Aerobic exercise improves self-reported sleep and quality of life in older adults with insomnia

OBJECTIVE To assess the efficacy of moderate aerobic physical activity with sleep hygiene education to improve sleep, mood and quality of life in older adults with chronic insomnia. METHODS Seventeen sedentary adults aged >or=55 years with insomnia (mean age 61.6 [SD±4.3] years; 16 female) participated in a randomized controlled trial comparing 16 weeks of aerobic physical activity plus sleep hygiene to non-physical activity plus sleep hygiene. Eligibility included primary insomnia for at least 3 months, habitual sleep duration <6.5h and a Pittsburgh Sleep Quality Index (PSQI) score >5. Outcomes included sleep quality, mood and quality of life questionnaires (PSQI, Epworth Sleepiness Scale [ESS], Short-form 36 [SF-36], Center for Epidemiological Studies Depression Scale [CES-D]). RESULTS The physical activity group improved in sleep quality on the global PSQI (p<.0001), sleep latency (p=.049), sleep duration (p=.04), daytime dysfunction (p=.027), and sleep efficiency (p=.036) PSQI sub-scores compared to the control group. The physical activity group also had reductions in depressive symptoms (p=.044), daytime sleepiness (p=.02) and improvements in vitality (p=.017) compared to baseline scores. CONCLUSION Aerobic physical activity with sleep hygiene education is an effective treatment approach to improve sleep quality, mood and quality of life in older adults with chronic insomnia.

Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging

Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non–rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep–dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life.

β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation

Independent evidence associates β-amyloid pathology with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here we show that β-amyloid burden in medial prefrontal cortex (mPFC) correlates significantly with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation was not direct, but instead statistically depended on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly.

Systematic evaluation of Axis-I DSM diagnoses in delayed sleep phase disorder and evening-type circadian preference.

BACKGROUND Alterations in circadian rhythms can have profound effects on mental health. High co-morbidity for psychiatric disorders has been observed in patients with circadian rhythm disorders, such as delayed sleep phase disorder (DSPD), and in those with an evening-type circadian preference. The aim of this study was to systematically determine the prevalence and type of Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM IV) Axis-I disorders in those with DSPD compared to evening-type controls. METHODS Forty-eight DSPD and 25 evening-type participants took part in this study. Sleep and wake parameters were assessed with actigraphy, diary and questionnaires (Pittsburgh Sleep Quality Index (PSQI) and Functional Outcomes of Sleep Questionnaire (FOSQ). Evening-type preference was defined by the Horne-Ostberg questionnaire. DSPD was determined by an interview according to International Classification of Sleep Disorders criteria. Current and past diagnoses of psychiatric disorders were assessed with a Structured Clinical Interview for DSM-IV disorders. RESULTS DSPD was associated with a later wake time, longer sleep time, higher PSQI score and lower Horne-Ostberg and FOSQ scores compared to evening-types. There were no significant differences in the prevalence or type of Axis-I disorders between those with DSPD or evening-type preference. Over 70% of participants met criteria for at least one past Axis-I disorder. Approximately 40% of both the DSPD and evening-types met criteria for a past diagnosis of mood, anxiety (most frequently phobia) or substance-use disorders. Evening types were more likely to have a past diagnosis of more than one Axis-I disorder. CONCLUSIONS These results highlight the important link between circadian rhythms and mental disorders. Specifically, an evening circadian chronotype regardless of DSPD status is associated with a risk for anxiety, depressive or substance-use disorders.

Impaired Prefrontal Sleep Spindle Regulation of Hippocampal-Dependent Learning in Older Adults

A hallmark feature of cognitive aging is a decline in the ability to form new memories. Parallel to these cognitive impairments are marked disruptions in sleep physiology. Despite recent evidence in young adults establishing a role for sleep spindles in restoring hippocampal-dependent memory formation, the possibility that disrupted sleep physiology contributes to age-related decline in hippocampal-dependent learning remains unknown. Here, we demonstrate that reduced prefrontal sleep spindles by over 40% in older adults statistically mediates the effects of old age on next day episodic learning, such that the degree of impaired episodic learning is explained by the extent of impoverished prefrontal sleep spindles. In addition, prefrontal spindles significantly predicted the magnitude of impaired next day hippocampal activation, thereby determining the influence of spindles on post-sleep learning capacity. These data support the hypothesis that disrupted sleep physiology contributes to age-related cognitive decline in later life, the consequence of which has significant treatment intervention potential.

Neurobiology of Sleep

The neurobiology of sleep is introduced in the context of interacting wake and sleep systems. Specifically, the transitions from wake to sleep and from non-rapid eye movement to rapid eye movement sleep are discussed based on the flip-flop switch hypothesis. Regulation of wake and sleep according to the opposing homeostatic and circadian systems are also presented.

Hyperinflation is associated with lower sleep efficiency in COPD with co-existent obstructive sleep apnea.

ABSTRACT Prior research has shown that individuals with obstructive lung disease are at risk for sleep fragmentation and poor sleep quality. We postulated that patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (known as overlap syndrome) who have more severe lung disease, as measured by lung hyperinflation (inspiratory capacity/total lung capacity), would have greater sleep disturbances independent of traditional measures of sleep apnea. We performed a retrospective chart review of consecutive patients evaluated and treated in an academic pulmonary clinic for overlap syndrome. Pulmonary function tests and polysomnogram data were collected. Thirty patients with overlap syndrome were included in the analysis. We found significant univariable associations between sleep efficiency and apnea/hypopnea index (β = −0.285, p = 0.01) and between sleep efficiency and lung hyperinflation (β = 0.654, p = 0.03). Using multivariable linear regression, the relationship between sleep efficiency and lung hyperinflation remained significant (β = 1.13, p = 0.02) after adjusting for age, sex, body mass index, apnea/hypopnea index, FEV1% predicted, oxygen saturation nadir, medications, and cardiac disease. We conclude that increased severity of hyperinflation is associated with worse sleep efficiency, independent of apnea and nocturnal hypoxemia. The mechanisms underlying this observation are uncertain. We speculate that therapies aimed at reducing lung hyperinflation may improve sleep quality in patients with overlap syndrome.

Sleep patterns among rural Chinese twin adolescents.

OBJECTIVE To examine sleep patterns and influencing factors (age, gender, Tanner Stage, weekday vs. weekend, and pre-sleep activity) among rural Chinese adolescents. METHODS This is a prospective study among 621 adolescents aged 11-20 years (341 males) using both a questionnaire and sleep diary to obtain bedtime, wake-up time, sleep latency, and total sleep time (TST). RESULTS The median TST was 8.6h on weekdays and 9.4h on weekends. Despite absence of late night social pressure and computers, a U-shaped TST pattern was observed across age and Tanner Stage, with a nadir around age 15-16 years or Tanner IV. Bedtimes became progressively later with age and Tanner Stage, while wake-up time was considerably earlier for school students or up to Tanner IV. Later wake-up times and longer TST on weekends were seen in school students, but not in non-school adolescents (>17 years). Pre-sleep activity, like reading or studying, was related to later bedtime, earlier wake-up time, and shorter TST in both genders. CONCLUSIONS Age, Tanner Stage, and pre-sleep activity affected sleep patterns in this sample of rural Chinese adolescents. Later bedtime coupled with earlier wake-up time associated with academic demand appear to be important contributors to sleep loss among school students.

Chicago healthy aging study: Objectives and design

Investigators in the Chicago Healthy Aging Study (CHAS) reexamined 1,395 surviving participants aged 65-84 years (28% women) from the Chicago Heart Association Detection Project in Industry (CHA) 1967-1973 cohort whose cardiovascular disease (CVD) risk profiles were originally ascertained at ages 25-44 years. CHAS investigators reexamined 421 participants who were low-risk (LR) at baseline and 974 participants who were non-LR at baseline. LR was defined as having favorable levels of 4 major CVD risk factors: serum total cholesterol level <200 mg/dL and no use of cholesterol-lowering medication; blood pressure 120/≤80 mm Hg and no use of antihypertensive medication; no current smoking; and no history of diabetes or heart attack. While the potential of LR status in overcoming the CVD epidemic is being recognized, the long-term association of LR with objectively measured health in older age has not been examined. It is hypothesized that persons who were LR in 1967-1973 and have survived to older age will have less clinical and subclinical CVD, lower levels of inflammatory markers, and better physical performance/functioning and sleep quality. Here we describe the rationale, objectives, design, and implementation of this longitudinal epidemiologic study, compare baseline and follow-up characteristics of participants and nonparticipants, and highlight the feasibility of reexamining study participants after an extended period postbaseline with minimal interim contact.

Insurance Decisions about Obesity Surgery: A New Type of Randomization?

Background: Studies of obesity surgery are frequently criticized for lack of an appropriate non-operative control arm. Additionally, insurance approval for coverage of these procedures can be difficult to obtain by patients and caregivers. This retrospective study tested the hypothesis that the insurance preapproval process would yield well-matched operative and non-operative treatment groups which could simulate a randomization process. Methods: Of 466 patients deemed to be appropriate candidates for surgery, 58% ultimately received surgical therapy. Roux-en-Y gastric bypass (RYGBP) was performed on 244 patients who were compared with 187 patients who did not undergo surgery (NonOP). Results: The groups were similar in gender (81% female), age (39 yr), and Body Mass Index (52 kg/m2). The percentage of African Americans in the NonOP group was greater.The distribution of comorbid conditions among the groups were similar. Conclusions: The insurance approval process results in a reasonable control group for parameters except race.