Smart Phone/Ecological Momentary Assessment of Sleep and Daytime Symptoms Among Older Adults With Insomnia.

OBJECTIVES: To employ smart phone/ecological momentary assessment (EMA) methods to evaluate the impact of insomnia on daytime symptoms among older adults. DESIGN: Prospective cohort study SETTING: Academic medical center PARTICIPANTS: Twenty-nine older adults with insomnia (M age = 67.5 ± 6.6 years, 69% women) and 34 healthy sleepers (M age = 70.4 ± 5.6 years, 65% women). MEASUREMENTS: Participants wore an actigraph, completed daily sleep diaries, and completed the Daytime Insomnia Symptoms Scale (DISS) via smart phone 4x/day for 2 weeks (i.e., 56 survey administrations across 14 days). RESULTS: Relative to healthy sleepers, older adults with insomnia demonstrated more severe insomnia symptoms in all DISS domains (alert cognition, positive mood, negative mood, and fatigue/sleepiness). A series of mixed model analyses were performed using the Benjamini-Hochberg procedure for correcting false discovery rate (BH-FDR) and an adjusted p-value <0.05. Among older adults with insomnia, all five prior-night sleep diary variables (sleep onset latency, wake after sleep onset, sleep efficiency, total sleep time, and sleep quality) were significantly associated with next-day insomnia symptoms (i.e., all four DISS domains). The median, first and third quintiles of the effect sizes (R2) of the association analyses were 0.031 (95% confidence interval (CI: [0.011,0.432]), 0.042(CI: [0.014,0.270]), 0.091 (CI:[0.014,0.324]). CONCLUSION: Results support the utility of smart phone/EMA assessment among older adults with insomnia. Clinical trials incorporating smart phone/EMA methods, including EMA as an outcome measure, are warranted.

Exercise interventions preserve hippocampal volume: A meta-analysis.

Hippocampal volume is a marker of brain health and is reduced with aging and neurological disease. Exercise may be effective at increasing and preserving hippocampal volume, potentially serving as a treatment for conditions associated with hippocampal atrophy (e.g., dementia). This meta-analysis aimed to identify whether exercise training has a positive effect on hippocampal volume and how population characteristics and exercise parameters moderate this effect. Studies met the following criteria: (a) controlled trials; (b) interventions of physical exercise; (c) included at least one time-point of hippocampal volume data before the intervention and one after; (d) assessed hippocampal volume using either manual or automated segmentation algorithms. Animal studies, voxel-based morphometry analyses, and multi-modal interventions (e.g., cognitive training or meditation) were excluded. The primary analysis in n = 23 interventions from 22 published studies revealed a significant positive effect of exercise on total hippocampal volume. The overall effect was significant in older samples (65 years of age or older) and in interventions that lasted over 24 weeks and had less than 150 min per week of exercise. These findings suggest that moderate amounts of exercise for interventions greater than 6 months have a positive effect on hippocampal volume including in older populations vulnerable to hippocampal atrophy.

Physical Activity and Cognition: A Mediating Role of Efficient Sleep.

OBJECTIVE: Physical activity benefits executive control, but the mechanism through which this benefit occurs is unclear. Sleep is a candidate mechanism given that it improves with exercise and has restorative effects on the prefrontal cortex. The present cross-sectional study examined the mediating role of sleep in the relationship between physical activity and executive control in young and older adults. PARTICIPANTS: Young (n = 59) and older (n = 53) community-dwelling adults ages 21-30 and 55-80. METHODS: Participants wore an accelerometer for one week to assess sleep efficiency, total sleep time, and physical activity, operationalized as metabolic equivalent of task (METs) during time spent awake. Cognition was assessed in the laboratory across multiple measures of executive control, memory recall, and processing speed. Mediation analyses tested the role of sleep efficiency in the cross-sectional relationship between METs and cognitive performance accounting for age, sex, and education. RESULTS: METs were significantly associated with performance before, but not after accounting for covariates. METs were associated with sleep efficiency but not total sleep time. Sleep efficiency, but not total sleep time, mediated the relationship between METs and working memory, switching, verbal ability and fluency, and recall. Age group did not moderate the mediating role of sleep efficiency in the relationship between METs and performance. CONCLUSION: Sleep efficiency is one pathway by which physical activity may be associated with executive control across young and older adults.

The role of non-rapid eye movement slow-wave activity in prefrontal metabolism across young and middle-aged adults.

Electroencephalographic slow-wave activity (0.5-4 Hz) during non-rapid eye movement (NREM) sleep is a marker for cortical reorganization, particularly within the prefrontal cortex. Greater slow wave activity during sleep may promote greater waking prefrontal metabolic rate and, in turn, executive function. However, this process may be affected by age. Here we examined whether greater NREM slow wave activity was associated with higher prefrontal metabolism during wakefulness and whether this relationship interacted with age. Fifty-two participants aged 25-61 years were enrolled into studies that included polysomnography and a (18) [F]-fluoro-deoxy-glucose positron emission tomography scan during wakefulness. Absolute and relative measures of NREM slow wave activity were assessed. Semiquantitative and relative measures of cerebral metabolism were collected to assess whole brain and regional metabolism, focusing on two regions of interest: the dorsolateral prefrontal cortex and the orbitofrontal cortex. Greater relative slow wave activity was associated with greater dorsolateral prefrontal metabolism. Age and slow wave activity interacted significantly in predicting semiquantitative whole brain metabolism and outside regions of interest in the posterior cingulate, middle temporal gyrus and the medial frontal gyrus, such that greater slow-wave activity was associated with lower metabolism in the younger participants and greater metabolism in the older participants. These results suggest that slow-wave activity is associated with cerebral metabolism during wakefulness across the adult lifespan within regions important for executive function.

Changes in Cognitive Performance Are Associated with Changes in Sleep in Older Adults With Insomnia.

The present study examined sleep features associated with cognition in older adults and examined whether sleep changes following insomnia treatment were associated with cognitive improvements. Polysomnography and cognition (recall, working memory, and reasoning) were assessed before and after an insomnia intervention (Brief Behavioral Treatment of Insomnia [BBTI] or information control [IC]) in 77 older adults with insomnia. Baseline wake-after-sleep-onset (WASO) was associated with recall. Greater NREM (nonrapid eye movement) delta power and lower NREM sigma power were associated with greater working memory and reasoning. The insomnia intervention did not improve performance. However, increased absolute delta power and decreased relative sigma power were associated with improved reasoning. Findings suggest that improvements in executive function may occur with changes in NREM architecture.

Sleep continuity and total sleep time are associated with task-switching and preparation in young and older adults.

Ageing is associated with changes in sleep and decline executive functions, such as task-switching and task preparation. Given that sleep affects executive function, age-related changes in executive function may be attributable to changes in sleep. The present study used a sleep detection device to examine whether or not wake time after sleep onset and total sleep time moderated age differences in task-switching performance and participants' ability to reduce switch costs when given time to prepare. Participants were cognitively healthy [Mini Mental State Examination > 26] younger (n = 54; mean age = 22.9; 67.8% female) and older (n = 45; mean age 62.8; 71.1% female) adults. Using a task-switching paradigm, which manipulated preparation time, we found that smaller global switch costs were associated with lower wake time after sleep onset and longer total sleep time. Greater preparation effects on local switch costs and adoption of a task-set were associated with lower wake time after sleep onset, although this effect was significant only in older adults when stratified by age group. This association was independent of inhibition and working memory abilities. The lack of interactions between sleep and age group indicated that age differences in switch costs were not moderated by better sleep. Our results suggest that young and older adults may benefit similarly from lower wake time after sleep onset and longer total sleep time in overall performance, and individuals with less wake time after sleep onset are more likely to engage preparatory strategies to reduce switch costs and boost task-switching performance.

Characterization of pulsations in the brain and cerebrospinal fluid using ultra-high field magnetic resonance imaging.

The development of innovative non-invasive neuroimaging methods and biomarkers is critical for studying brain disease. Imaging of cerebrospinal fluid (CSF) pulsatility may inform the brain fluid dynamics involved in clearance of cerebral metabolic waste. In this work, we developed a methodology to characterize the frequency and spatial localization of whole brain CSF pulsations in humans. Using 7 Tesla (T) human magnetic resonance imaging (MRI) and ultrafast echo-planar imaging (EPI), in-vivo images were obtained to capture pulsations of the CSF signal. Physiological data were simultaneously collected and compared with the 7 T MR data. The primary components of signal pulsations were identified using spectral analysis, with the most evident frequency bands identified around 0.3, 1.2, and 2.4 Hz. These pulsations were mapped spatially and temporally onto the MR image domain and temporally onto the physiological measures of electrocardiogram and respiration. We identified peaks in CSF pulsations that were distinct from peaks in grey matter and white matter regions. This methodology may provide novel in vivo biomarkers of disrupted brain fluid dynamics.

A pilot time-in-bed restriction intervention behaviorally enhances slow-wave activity in older adults.

Introduction: Identifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with greater sleep efficiency and non-rapid eye movement slow-wave activity (SWA) (0.5-4 Hz electroencephalographic activity) tend to exhibit better memory and cognitive abilities. Paradoxically, long total sleep times are consistently associated with poorer cognition in older adults. Thus, maximizing sleep efficiency and SWA may be a priority relative to increasing mere total sleep time. As clinical behavioral sleep treatments do not consistently enhance SWA, and propensity for SWA increases with time spent awake, we examined with a proof-of concept pilot intervention whether a greater dose of time-in-bed (TiB) restriction (75% of habitual TiB) would increase both sleep efficiency and SWA in older adults with difficulties staying asleep without impairing memory performance. Methods: Participants were adults ages 55-80 with diary-reported sleep efficiency <90% and wake after sleep onset (WASO) >20 min. Sleep diary, actigraphy, polysomnography (PSG), and paired associate memory acquisition and retention were assessed before and after a week-long TiB restriction intervention (n = 30). TiB was restricted to 75% of diary-reported habitual TiB. A comparison group of n = 5 participants repeated assessments while following their usual sleep schedule to obtain preliminary estimates of effect sizes associated with repeated testing. Results: Subjective and objective sleep measures robustly improved in the TiB restriction group for sleep quality, sleep depth, sleep efficiency and WASO, at the expense of TiB and time spent in N1 and N2 sleep. As hypothesized, SWA increased robustly with TiB restriction across the 0.5-4 Hz range, as well as subjective sleep depth, subjective and objective WASO. Despite increases in sleepiness ratings, no impairments were found in memory acquisition or retention. Conclusion: A TiB restriction dose equivalent to 75% of habitual TiB robustly increased sleep continuity and SWA in older adults with sleep maintenance difficulties, without impairing memory performance. These findings may inform long-term behavioral SWA enhancement interventions aimed at improving memory performance and risk for cognitive impairments.

The Interactive Role of Sleep and Circadian Rhythms in Episodic Memory in Older Adults.

Adequate sleep is essential for healthy physical, emotional, and cognitive functioning, including memory. However, sleep ability worsens with increasing age. Older adults on average have shorter sleep durations and more disrupted sleep compared with younger adults. Age-related sleep changes are thought to contribute to age-related deficits in episodic memory. Nonetheless, the nature of the relationship between sleep and episodic memory deficits in older adults is still unclear. Further complicating this relationship are age-related changes in circadian rhythms such as the shift in chronotype toward morningness and decreased circadian stability, which may influence memory abilities as well. Most sleep and cognitive aging studies do not account for circadian factors, making it unclear whether age-related and sleep-related episodic memory deficits are partly driven by interactions with circadian rhythms. This review will focus on age-related changes in sleep and circadian rhythms and evidence that these factors interact to affect episodic memory, specifically encoding and retrieval. Open questions, methodological considerations, and clinical implications for diagnosis and monitoring of age-related memory impairments are discussed.

Cardiometabolic function in retired night shift workers and retired day workers.

Night shift work is associated with poor cardiometabolic outcomes, even post-retirement. However, the characteristics of cardiometabolic function in retired night shift workers (RNSW) compared to retired day workers (RDW) are not well-understood. Rigorous characterization of cardiometabolic dysfunction in RNSW and RDW will inform targeted risk stratification for RNSW. This observational study evaluated whether RNSW (n = 71) had poorer cardiometabolic function than RDW (n = 83). We conducted a multimodal assessment of cardiometabolic function including metabolic syndrome prevalence, brachial artery flow-mediated dilation, and carotid intima-media thickness. Main analyses tested overall group differences. Sex-stratified follow-up analyses tested group differences separately in men and women. RNSW had 2.6-times higher odds of metabolic syndrome prevalence than RDW in unadjusted analyses (95% CI [1.1,6.3]); this association was not significant when adjusting for age, race and education. RNSW and RDW (Mage = 68.4; 55% female) did not differ in percent flow-mediated dilation or carotid intima-media thickness. In sex-stratified analyses, women RNSW had 3.3-times higher odds of having high body mass index than women RDW (95% CI [1.2,10.4]). Men RNSW had 3.9-times higher odds of having high triglycerides than men RDW (95% CI [1.1,14.2]). No other group differences were observed. We found mixed evidence that night shift work exposure was associated with cardiometabolic dysfunction in retirement, possibly in a sex-specific manner.

Characterization of oscillations in the brain and cerebrospinal fluid using ultra-high field magnetic resonance imaging.

Development of innovative non-invasive neuroimaging methods and biomarkers are critical for studying brain disease. In this work, we have developed a methodology to characterize the frequency responses and spatial localization of oscillations and movements of cerebrospinal fluid (CSF) flow in the human brain. Using 7 Tesla human MRI and ultrafast echo-planar imaging (EPI), in-vivo images were obtained to capture CSF oscillations and movements. Physiological data was simultaneously collected and correlated with the 7T MR data. The primary components of CSF oscillations were identified using spectral analysis (with frequency bands identified around 0.3Hz, 1.2Hz and 2.4Hz) and were mapped spatially and temporally onto the MR image domain and temporally onto the physiological domain. The developed methodology shows a good consistency and repeatability (standard deviation of 0.052 and 0.078 for 0.3Hz and 1.2Hz bands respectively) in-vivo for potential brain dynamics and CSF flow and clearance studies.

Age-related decline in controlled retrieval: the role of the PFC and sleep.

Age-related cognitive impairments often include difficulty retrieving memories, particularly those that rely on executive control. In this paper we discuss the influence of the prefrontal cortex on memory retrieval, and the specific memory processes associated with the prefrontal cortex that decline in late adulthood. We conclude that preretrieval processes associated with preparation to make a memory judgment are impaired, leading to greater reliance on postretrieval processes. This is consistent with the view that impairments in executive control significantly contribute to deficits in controlled retrieval. Finally, we discuss age-related changes in sleep as a potential mechanism that contributes to deficiencies in executive control that are important for efficient retrieval. The sleep literature points to the importance of slow-wave sleep in restoration of prefrontal cortex function. Given that slow-wave sleep significantly declines with age, we hypothesize that age-related changes in slow-wave sleep could mediate age-related decline in executive control, manifesting a robust deficit in controlled memory retrieval processes. Interventions, like physical activity, that improve sleep could be effective methods to enhance controlled memory processes in late life.

Effects of continuous positive airway pressure treatment on sleep architecture in adults with obstructive sleep apnea and type 2 diabetes.

Obstructive sleep apnea (OSA) severely impacts sleep and has long-term health consequences. Treating sleep apnea with continuous positive airway pressure (CPAP) not only relieves obstructed breathing, but also improves sleep. CPAP improves sleep by reducing apnea-induced awakenings. CPAP may also improve sleep by enhancing features of sleep architecture assessed with electroencephalography (EEG) that maximize sleep depth and neuronal homeostasis, such as the slow oscillation and spindle EEG activity, and by reducing neurophysiological arousal during sleep (i.e., beta EEG activity). We examined cross-sectional differences in quantitative EEG characteristics of sleep, assessed with power spectral analysis, in 29 adults with type 2 diabetes treated with CPAP and 24 adults undergoing SHAM CPAP treatment (total n = 53). We then examined changes in spectral characteristics of sleep as the SHAM group crossed over to active CPAP treatment (n = 19). Polysomnography (PSG) from the CPAP titration night was used for the current analyses. Analyses focused on EEG frequencies associated with sleep maintenance and arousal. These included the slow oscillation (0.5-1 Hz), sigma activity (12-16 Hz, spindle activity), and beta activity (16-20 Hz) in F3, F4, C3, and C4 EEG channels. Whole night non-rapid eye movement (NREM) sleep and the first period of NREM spectral activity were examined. Age and sex were included as covariates. There were no group differences between CPAP and SHAM in spectral characteristics of sleep architecture. However, SHAM cross-over to active CPAP was associated with an increase in relative 12-16 Hz sigma activity across the whole night and a decrease in average beta activity across the whole night. Relative slow oscillation power within the first NREM period decreased with CPAP, particularly for frontal channels. Sigma and beta activity effects did not differ by channel. These findings suggest that CPAP may preferentially enhance spindle activity and mitigate neurophysiological arousal. These findings inform the neurophysiological mechanisms of improved sleep with CPAP and the utility of quantitative EEG measures of sleep as a treatment probe of improvements in neurological and physical health with CPAP.

Physical Exertion Partially Mitigates Task-Switching Deficits From Sleep Loss: Implications for Firefighters.

OBJECTIVE: The aim of the study is to investigate effects of physical exertion on cognitive deficits from sleep loss under conditions that mimic a firefighting scenario. METHODS: Twenty-four male participants completed a crossover study design with 3 conditions: total sleep deprivation, sleep disruption (three 60-minute awakenings), and rested control. Participants then completed 50 minutes of a physical exertion task involving treadmill exercise in a heated room while wearing firefighter protective clothing. Vigilant attention and task-switching performance were assessed pre- and post-sleep manipulation and pre- and post-physical exertion. Vigilant attention was also assessed mid-physical exertion. RESULTS: Total sleep deprivation and sleep disruption increased attentional lapses and task-switching RT. Total sleep deprivation additionally reduced task-switching accuracy. Performance after physical exertion improved only for task-switching RT after total sleep deprivation. CONCLUSIONS: Physical exertion selectively mitigated task-switching RT deficits from the most severe sleep loss condition, total sleep deprivation.

Effects of task-set adoption on ERP correlates of controlled and automatic recognition memory.

Successful memory retrieval depends not only on memory fidelity but also on the mental preparedness on the part of the subject. ERP studies of recognition memory have identified two topographically distinct ERP components, the FN400 old/new effect and the late posterior component (LPC) old/new effect, commonly associated with familiarity and recollection, respectively. Here we used a task-switching paradigm to examine the extent to which adoption of a retrieval task-set influences FN400 and LPC old/new effects, in light of the presumption that recollection, as a control process, relies on the adoption of a retrieval task-set, but that familiarity-based retrieval does not. Behavioral accuracy indicated that source memory (experiment 2), but not item recognition (experiment 1), improved with task-set adoption. ERP data demonstrated a larger LPC on stay trials when a task-set had been adopted even with a simple recognition memory judgment. We conclude that adopting a retrieval task-set impacts recollection memory but not familiarity. These data indicate that attentional state immediately prior to retrieval can influence objective measures of recollection memory.

Does objectively-assessed sleep moderate the association between history of major depressive disorder and task-switching?

BACKGROUND: Executive function and psychomotor speed are consistently impaired in patients with major depressive disorder (MDD). Persistent cognitive impairments after depression remission are thought to reflect "scarring" from the neurotoxic effects of hypothalamic-pituitary-adrenal axis activity during a depressive episode. As sleep also deteriorates with depression and restores daytime executive functions, we examined whether adequate sleep could be protective against task-switching and psychomotor impairments associated with a history of MDD. METHODS: This cross-sectional study tested task-switching associations with MDD history, sleep, and their interaction to determine whether sleep continuity and sleep duration moderate the relationship between MDD history and task-switching performance. RESULTS: After adjusting for age, sex, education, current depressive symptoms, and use of anti-depressants, a history of MDD, particularly recurrent MDD, was associated with slower response speed and disproportionately lower accuracy on repetition trials compared to switch trials, reflecting impaired adoption of a task-set. Regardless of MDD history, higher wake after sleep onset and shorter total sleep time were associated with slower response times, but neither sleep measure moderated the association between depression history and task-switching performance. LIMITATIONS: This cross-sectional study cannot assess the causal direction of associations. One night of sleep in the laboratory was used to assess sleep and a single task-switching paradigm was used to assess executive function. CONCLUSIONS: These results suggest that longer, more continuous sleep is associated with greater psychomotor speed across healthy controls and those with a history of MDD, but MDD-task-switching associations are not mitigated by longer or more continuous sleep.

Slow-oscillation activity is reduced and high frequency activity is elevated in older adults with insomnia.

STUDY OBJECTIVES: High-frequency electroencephalographic activity (> 16 Hz activity) is often elevated during nonrapid eye movement sleep among individuals with insomnia, in line with the hyperarousal theory of insomnia. Evidence regarding sleep depth marked by slow-wave activity (< 4 Hz) is more mixed. Distinguishing subcomponents of slow-wave activity (slow-oscillation [< 1 Hz] or delta activity [1-4 Hz)]) may be critical in understanding these discrepancies, given that these oscillations have different neural generators and are functionally distinct. Here we tested the effects of insomnia diagnosis and insomnia treatment on nonrapid eye movement electroencephalography in older adults, distinguishing slow-oscillation and delta power. METHODS: In 93 older adults with insomnia and 71 good sleeper control participants (mean ages 68 years), effects of insomnia and cognitive behavioral therapy for insomnia (insomnia group only) on electroencephalographic spectral power were analyzed. Main effects and interactions with nonrapid eye movement period were assessed for the following frequency bands: slow-oscillation (0.5-1 Hz), delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), sigma (12-16 Hz), and beta (16-32 Hz). RESULTS: Slow-oscillation absolute and relative power were lower in the insomnia group compared with controls. There were no group differences in delta power. Insomnia was also associated with elevated 4-32 Hz absolute and relative power. After cognitive behavioral therapy for insomnia, absolute sigma and beta activity decreased. CONCLUSIONS: Deficits in slow-wave activity in insomnia are specific to the slow-oscillation. Elevated high frequency activity is reduced for sigma and beta power following cognitive behavioral therapy for insomnia . These findings inform the pathophysiology of insomnia, including the mechanisms underlying cognitive behavioral therapy for insomnia in older adults.

Infection with Herpes Simplex virus type 1 (HSV-1) and sleep: The dog that did not bark.

Persistent infection with Herpes Simplex viruses (HSV) and other brain infections is consistently associated with cognitive impairment. These infections can also affect sleep. Thus, sleep abnormalities could explain the cognitive dysfunction. We investigated the association between sleep variables and persistent HSV-1, HSV-2, cytomegalovirus (CMV) and Toxoplasma gondii (Tox) infections. Sleep data were collected from older adults with or without insomnia (N = 311, total); a subset completed polysomnographic and actigraphy studies (N = 145). No significant associations were found between the infections and insomnia or the remaining sleep variables following corrections for multiple comparisons. Sleep dysfunction is unlikely to explain the infection-related cognitive dysfunction.