Characterizing Behavioral Activity Rhythms in Older Adults Using Actigraphy.

Wrist actigraphy has been used to assess sleep in older adult populations for nearly half a century. Over the years, the continuous raw activity data derived from actigraphy has been used for the characterization of factors beyond sleep/wake such as physical activity patterns and circadian rhythms. Behavioral activity rhythms (BAR) are useful to describe individual daily behavioral patterns beyond sleep and wake, which represent important and meaningful clinical outcomes. This paper reviews common rhythmometric approaches and summarizes the available data from the use of these different approaches in older adult populations. We further consider a new approach developed in our laboratory designed to provide graphical characterization of BAR for the observed behavioral phenomenon of activity patterns across time. We illustrate the application of this new approach using actigraphy data collected from a well-characterized sample of older adults (age 60+) with osteoarthritis (OA) pain and insomnia. Generalized additive models (GAM) were implemented to fit smoothed nonlinear curves to log-transformed aggregated actigraphy-derived activity measurements. This approach demonstrated an overall strong model fit (R2 = 0.82, SD = 0.09) and was able to provide meaningful outcome measures allowing for graphical and parameterized characterization of the observed activity patterns within this sample.

Cardiovascular autonomic dysfunction in insomnia patients with objective short sleep duration.

Two phenotypes have been proposed: insomnia with objective near-normal sleep duration, related to increased psychological symptoms, and insomnia with objective short sleep duration, associated with cardiometabolic morbidity. Reduced heart rate variability has also been implicated in the pathophysiology of cardiometabolic disease; however, there are little data on whether cardiovascular function differs between patients with objective short sleep duration and near-normal sleep duration. Participants (Mage  = 49.9 ± 11.3 years; 62.8% female) were 180 adults with chronic insomnia (Mduration  = 15.7 ± 13.6). Objective sleep duration was based on total sleep time averaged across two consecutive nights of polysomnography and subjective sleep duration was based on 2-week sleep diaries. The sample was divided into two groups, with sleep duration shorter (polysomnography-total sleep time: n = 46; sleep diary: n = 95) or equal/longer (polysomnography-total sleep time: n = 134; sleep diary: n = 85) than 6 hr. Electrocardiogram data derived from polysomnography were used to obtain heart rate and heart rate variability during stage 2 (N2) and rapid eye movement sleep. Heart rate variability measures included absolute and normalized high-frequency component, an index of parasympathetic activation, and the ratio of low- to high-frequency (LF/HF ratio), an index of sympathovagal balance. After controlling for covariates (e.g., co-morbidity), patients with objective short sleep duration had reduced high-frequency (p < .05) and elevated low-frequency/high-frequency ratio (p = .036) and heart rate (p = .051) compared with patients with near-normal sleep duration. No differences were observed between phenotypes when subjective sleep duration was used. Insomnia patients with objective short sleep duration showed significantly dampened parasympathetic activation and increased sympathovagal imbalance relative to their counterparts with near-normal sleep duration. These findings highlight the importance of treating insomnia, as treatment may reduce the risk of cardiovascular disease.

The role of vulnerability in stress-related insomnia, social support and coping styles on incidence and persistence of insomnia.

Individuals who are more prone to experience situational insomnia under stressful conditions may also be at greater risk to develop subsequent insomnia. While cross-sectional data exist on the link between sleep reactivity (heightened vulnerability to stress-related insomnia) and insomnia, limited data exist on its predictive value. The aim of the study was to evaluate prospectively whether sleep reactivity was associated with increased risk of incident and persistent insomnia in a population-based sample of good sleepers. Social support and coping styles were also investigated as potential moderators. Participants were 1449 adults (Mage  = 47.4 years, standard deviation = 15.1; 41.2% male) without insomnia at baseline and evaluated four times over 3 years. Sleep reactivity was measured using the Ford Insomnia Response to Stress Test (FIRST). Additional measures included depressive symptoms, the frequency and perceived impact of stressful life events, social support and coping styles. After controlling for prior sleep history, depressive symptoms, arousal predisposition, stressful life events and perceived impact, individuals with higher sleep reactivity had an odds ratio (OR) of 1.56 [95% confidence interval (CI): 1.13-2.16], 1.41 (95% CI: 0.87-2.30) and 2.02 (95% CI: 1.30-3.15) of developing insomnia symptoms, syndrome and persistent insomnia, respectively. Social support and coping styles did not moderate these associations. Results suggest that heightened vulnerability to insomnia is associated with an increased risk of developing new-onset subsyndromal and persistent insomnia in good sleepers. Knowledge of premorbid differences is important to identify at-risk individuals, as this may help to develop more targeted prevention and intervention strategies for insomnia.

Insomnia Symptoms Are Associated with Measures of Functional Deterioration and Dementia Status in Adults with Down Syndrome at High Risk for Alzheimer's Disease.

Background: While obstructive sleep apnea (OSA) and insomnia symptoms in neurotypical populations are associated with Alzheimer's disease (AD), their association with dementia in adults with Down syndrome (DS) remains less clear, even though these symptoms are prevalent and treatable in DS. Understanding their associations with AD-related dementia status, cognitive impairment, and functional deterioration may lead to interventions to slow decline or disease progression in adults with DS. Objective: To characterize differences in OSA and insomnia symptom expression by dementia status, and to determine which sleep factors support dementia diagnosis. Methods: Multimodal consensus conference was used to determine dementia status in 52 adults with DS (52.2 ±â€Š6.4 years, 21 women). Cognitive impairment, adaptive behavior skills, and symptoms of OSA and insomnia were quantified using validated assessments for adults with DS and their primary informants. Results: A sex by dementia status interaction demonstrated that older women with DS and dementia had more severe terminal insomnia but not OSA symptoms relative to older women with DS who were cognitively stable (CS). Greater insomnia symptom severity was associated with greater functional impairments in social and self-care domains adjusting for age, sex, premorbid intellectual impairment, and dementia status. Conclusions: Insomnia symptoms are more severe in women with DS with dementia than in women with DS and no dementia, and regardless of dementia status or sex, more severe insomnia symptoms are associated with greater impairment in activities of daily living. These findings underscore the potential importance of early insomnia symptom evaluation and treatment in women with DS at risk of developing AD.

Cardiorespiratory fitness and circadian rhythms in adolescents: a pilot study.

Although cardiorespiratory fitness (CRF), an important marker of youth health, is associated with earlier sleep/wake schedule, its relationship with circadian rhythms is unclear. This study examined the associations between CRF and rhythm variables in adolescents. Eighteen healthy adolescents (10 females and 8 males; Mage = 14.6 ± 2.3 yr) completed two study visits on weekdays bracketing an ambulatory assessment during summer vacation. Visit 1 included in-laboratory CRF assessment (peak V̇o2) using a ramp-type progressive cycle ergometry protocol and gas exchange measurement, which was followed by 7-14 days of actigraphy to assess sleep/wake patterns and 24-h activity rhythms. During Visit 2, chronotype, social jetlag (i.e., the difference in midsleep time between weekdays and weekends), and phase preference were assessed using a questionnaire, and hourly saliva samples were collected to determine the dim light melatonin onset (DLMO) phase. All analyses were adjusted for sex, pubertal status, and physical activity. Greater peak V̇o2 was associated with earlier sleep/wake times and circadian phase measures, including acrophase, UP time, DOWN time, last activity peak (LAP) time, and chronotype (all P < 0.05). Peak V̇o2 was negatively associated with social jetlag (P = 0.02). In addition, the mixed-model analysis revealed a significant interaction effect between peak V̇o2 and actigraphy-estimated hour-by-hour activity patterns (P < 0.001), with the strongest effects observed at around the time of waking (0600-1000). In healthy adolescents, better CRF was associated with an earlier circadian phase and increased activity levels notably during the morning. Future studies are needed to investigate the longitudinal effects of the interactions between CRF and advanced rhythms on health outcomes.NEW & NOTEWORTHY In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (V̇o2)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults.

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults.

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality-graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes-map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

Latent anxiety in clinical depression is associated with worse recognition of emotional stimuli.

BACKGROUND: Major Depressive Disorder, characterized by cognitive affective biases, is a considerable public health challenge. Past work has shown that higher depressive symptoms are associated with augmented memory of negative stimuli. In contrast, anxiety symptoms have been associated with overgeneralization of emotional memories. Given the high comorbidity of depression and anxiety, it is critical to understand how cognitive affective biases are differentially associated with clinical symptoms. METHOD: We used continuous measures of depression (Beck Depression Inventory [BDI-II]) and anxiety (Beck Anxiety Inventory [BAI]) to evaluate an adult sample (N = 79; 18-41 years old, 58 female). Emotional memory discrimination and recognition memory were tested using an emotional discrimination task. We applied exploratory factor analysis to questions from the BAI and BDI-II to uncover latent constructs consisting of negative affect, anhedonia, somatic anxiety, and cognitive anxiety. RESULTS: We report evidence that anxious symptoms were associated with impaired recognition of negative items after accounting for age and sex. Our exploratory factor analysis revealed that impaired negative item recognition is largely associated with somatic and cognitive anxiety factors. LIMITATIONS: Interpretations in a mixed pathology sample, especially given collinearity among factors, may be difficult. CONCLUSIONS: We provide evidence that somatic and cognitive anxiety are related to impaired recognition memory for negative stimuli. Future clinical investigations should uncover the neurobiological basis supporting the link between recognition of negative stimuli and somatic/cognitive symptoms of anxiety.

Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to ß-amyloid positivity.

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, ß-amyloid-negative, older adults (mean ±â€…SD; 61.4 ±â€…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, ß-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 ß-amyloid positivity, thus offering a promising candidate therapeutic target to arrest cognitive decline associated with aging and AD.

Aerobic fitness and the sleeping brain of adolescents-a pilot study.

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.

Investigating psychological and physiological responses to the Trier Social Stress Test in young adults with insomnia.

OBJECTIVE: Stress and hyperarousal both contribute to insomnia. Elevated stress-related sleep reactivity is associated with hyperarousal, and might constitute a vulnerability to future insomnia. The present study examined acute stress-induced arousal and its association with nocturnal sleep. METHODS: Participants were 30 healthy adults (66.7% female, Mage = 26.7 years): 10 with insomnia (INS) and 20 good sleepers with high vulnerability (HV) or low vulnerability (LV) to insomnia. They underwent two consecutive nights of polysomnography. During the evening preceding the second night, the Trier Social Stress Test (TSST) was administered, and psychological and physiological arousal indices were assessed. RESULTS: The TSST elicited an increase in psychological and physiological arousal in all three groups. The INS group showed greater acute cortisol response (p < 0.05) and secretion at bedtime (p < 0.05), and higher pre-sleep cognitive arousal (p < 0.01) than the LV group; HV participants did not significantly differ from those in the INS or the LV group. Increased cortisol response and elevated sympathovagal imbalance (ie, low frequency/high frequency ratio) were each significantly associated with longer nocturnal awakenings (p = 0.048, p = 0.037, respectively). Heightened blood pressure was significantly associated with prolonged sleep onset latency, and reduced total sleep time and sleep efficiency (all ps < 0.05). CONCLUSIONS: These findings support the hyperarousal conceptualization of insomnia and indirectly suggest that increased stress reactivity and bedtime hyperarousal might represent a trait-like vulnerability in certain good sleepers. More research is warranted to validate and expand these preliminary findings.

How Hyperarousal and Sleep Reactivity Are Represented in Different Adult Age Groups: Results from a Large Cohort Study on Insomnia.

Hyperarousal is a 24-h state of elevated cognitive and physiological activation, and is a core feature of insomnia. The extent to which sleep quality is affected by stressful events-so-called sleep reactivity-is a vulnerability factor for developing insomnia. Given the increasing prevalence of insomnia with age, we aimed to investigate how hyperarousal and sleep reactivity were related to insomnia severity in different adult age groups. Data were derived from a large cohort study investigating the natural history of insomnia in a population-based sample (n = 1693). Baseline data of the Arousal Predisposition Scale (APS) and Ford Insomnia Response to Stress Test (FIRST) were examined across age and sleep/insomnia subgroups: 25-35 (n = 448), 35-45 (n = 528), and 45-55 year olds (n = 717); good sleepers (n = 931), individuals with insomnia symptoms (n = 450), and individuals with an insomnia syndrome (n = 312). Results from factorial analyses of variance (ANOVA) showed that APS scores decreased with increasing age, but increased with more severe sleep problems. FIRST scores were not significantly different across age groups, but showed the same strong increase as a function of sleep problem severity. The findings indicate that though arousal predisposition and sleep reactivity increase with more severe sleep problems, only arousal decreases with age. How arousing events affect an individual during daytime thus decreases with age, but how this arousal disrupts sleep is equivalent across different adult age groups. The main implication of these findings is that treatment of insomnia could be adapted for different age groups and take into consideration vulnerability factors such as hyperarousal and stress reactivity.

Nocturnal heart rate variability in patients treated with cognitive-behavioral therapy for insomnia.

OBJECTIVE: Insomnia and reduced heart rate variability (HRV) increase the risk of cardiovascular disease and its precursors; thus, it is important to evaluate whether treatment for insomnia provides cardiovascular safeguards. The present study aimed to evaluate potential cardiovascular benefits of cognitive behavioral therapy for insomnia (CBT-I). METHOD: The present study included 65 patients treated for chronic insomnia (M = 51.8 years, SD = 10.0; 66.2% female) at a university hospital. Patients received CBT-I over a 6-week period, and change scores from pre- to posttreatment derived from the Insomnia Severity Index, sleep diary, and polysomnography (PSG) were used as indices of sleep improvement. HRV variables (i.e., low frequency [LF], high frequency [HF], and the ratio of low to high frequency [LF:HF ratio]) were derived for Stage 2 (S2) and rapid-eye movement (REM) sleep at pre- and posttreatment. High HF (i.e., parasympathetic activity) and/or low LF:HF ratio (i.e., sympathovagal balance) were used as indices of HRV improvement. RESULTS: Following therapy, sleep improvements, particularly for sleep onset latency, were related with reduced HF in S2 (r = .30, p < .05) and in REM (r = .36, p < .01). A trend was also observed between reduced insomnia symptoms and increased HF in REM (r = -.21, p < .10). CONCLUSIONS: Findings suggest that contrary to expectations, sleep improvements following CBT-I were associated with reduced parasympathetic activation and increased sympathovagal balance. Although preliminary, these results raise the question as to whether insomnia treatment might play a role in physiological changes associated with cardiovascular anomalies. Future research is needed to examine the long-term impact of treatment as a preventative tool against insomnia-related morbidity. (PsycINFO Database Record

Temporal Stability of the Ford Insomnia Response to Stress Test (FIRST).

STUDY OBJECTIVES: The Ford Insomnia Response to Stress Test (FIRST) is a self-report tool that measures sleep reactivity (i.e., vulnerability to experience situational insomnia under stressful conditions). Sleep reactivity has been termed a "trait-like" vulnerability; however, evidence of its long-term stability is lacking. The main objective of the current psychometric study was to investigate the temporal stability of the FIRST over two 6-mo intervals in a population-based sample of adults with and without insomnia. The temporal stability of the FIRST was also compared with the temporal stability of other scales associated with insomnia (trait-anxiety, arousability). METHODS: Participants included 1,122 adults (mean age = 49.9 y, standard deviation = 14.8; 38.8% male) presenting with an insomnia syndrome (n = 159), insomnia symptoms (n = 152), or good sleep (n = 811). Participants completed the FIRST, the State-Trait Anxiety Inventory (trait-anxiety), and the Arousal Predisposition Scale (arousability) on three different occasions: baseline and at 6- and 12-mo follow-up. Intraclass correlation coefficients (ICCs) were computed for all scales (baseline to 6 mo and 6 to 12 mo). RESULTS: The FIRST yielded strong temporal stability from baseline to 6 mo among those with insomnia syndrome (ICC = 0.81), symptoms (ICC = 0.78), and good sleep (ICC = 0.81). Similar results were observed for 6 to 12 mo among those with insomnia syndrome (ICC = 0.74), insomnia symptoms (ICC = 0.82), and good sleep (ICC = 0.84). The stability of the FIRST was not comparable with the stability of trait-anxiety, but was somewhat comparable with the stability of arousability. CONCLUSIONS: Overall, the FIRST is a temporally reliable stable scale over 6-mo intervals. Future research is needed to corroborate the stability and trait-like measures of sleep reactivity with physiological, behavioural and personality measures.