Insomnia as an Independent Predictor of Incident Cardiovascular Disease in HIV: Data from the Veterans Aging Cohort Study

Background: Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown. Methods: Using the Veterans Aging Cohort Study-Survey Cohort, insomnia symptoms were measured and dummy coded with the item, “Difficulty falling or staying asleep?” (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with VA and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded. Results: HIV-infected (N=3,108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics (HR=1.64, 95%CI=1.16-2.31, p=.005), CVD risk factors (HR=1.62, 95%CI=1.14-2.30, p=.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, cocaine use; HR=1.70, 95%CI=1.19-2.43, p=.003), and HIV-specific factors (HIV-1 RNA, CD4+ T-cell count, ART; HR=1.66, 95%CI=1.16-2.37, p=.005). Additional adjustment for non-benzodiazepine sleep medication (HR=1.62, 95%CI=1.13-2.32, p=.009) did not attenuate the association; however, it fell short of significance at p < .01 after adjustment for depressive symptoms (HR=1.51, 95%CI=0.98-2.32, p=.060) or antidepressant medication (HR=1.51, 95%CI=1.04-2.19, p=.031). Conclusion: Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV

Perspective on Sleep and Aging

There is a strong body of data directly interrelating sleep problems with mood disorders. There is a growing data base directly associating sleep disorders with attention and memory problems. Motor disorders, especially involving the dopaminergic system, may produce sleep problems, including a possible association between disordered sleep and nocturnal falls. Sleep disorders may be causal conditions for metabolic diseases and increased risk for morbidity and mortality. Sleep and health are directly interrelated. To further probe these issues, especially as related to the aging process, investigators need to utilize tools and concepts from genomics and epigenetics, proteomics, metabolomics, any future …omics, molecular neuroimaging, and cognitive neuroscience

Do sleep difficulties exacerbate deficits in sustained attention following traumatic brain injury?

Sustained attention has been shown to be vulnerable following traumatic brain injury (TBI). Sleep restriction and disturbances have been shown to negatively affect sustained attention. Sleep disorders are common but under-diagnosed after TBI. Thus, it seems possible that sleep disturbances may exacerbate neuropsychological deficits for a proportion of individuals who have sustained a TBI. The aim of this prospective study was to examine whether poor sleepers post-TBI had poorer sustained and general attentional functioning than good sleepers post-TBI. Retrospective subjective, prospective subjective, and objective measures were used to assess participants’ sleep. The results showed that the poor sleep group had significantly poorer sustained attention ability than the good sleep group. The differences on other measures of attention were not significant. This study supports the use of measures that capture specific components of attention rather than global measures of attention, and highlights the importance of assessing and treating sleep problems in brain injury rehabilitation

Sleep/wake activity and energy expenditure in overweight and obese obstructive sleep apnea patients : a pre- and post-CPAP comparison.

Overweight and obesity is a major contributing factor in an estimated 70% of all obstructive sleep apnea (OSA) cases. Approximately five percent of the adult population has OSA, and the numbers continue to soar with the rising prevalence of obesity. As a primary therapy, continuous positive airway pressure (CPAP) has demonstrated improvement in many comorbidities associated with both OSA and obesity. Although anecdotal and clinical references support increased energy, activity, and weight loss as a potential benefit of CP AP treatment, there remains little evidence to endorse CP AP as a significant weight-reduction measure for overweight and obese OSA patients. The purpose of this study was to examine sleep/wake activity and energy expenditure, pre- and post-CP AP treatment, in adult overweight and obese patients with OSA. A prospective, observational, longitudinal study design was employed to assess 24-hour actigraphic measures of sleep/wake activity and energy expenditure prior and subsequent to CPAP therapy. Analysis of variance (ANOVA) using repeated measures was performed to identify overall differences between pre-CP AP and one week post-CPAP and pre-CPAP and one month and post-CPAP sleep activity, wake activity, and 24-hour energy expenditure. Sixty-nine subjects were consented, with a total of 35 subjects completing the study. Data analyses revealed statistically significant mean differences in sleep activity, wake activity, and energy expenditure from pre-CPAP to post-CPAP at one week and one month. At baseline, and continuing through one week post-CPAP and one month post-CPAP, the CPAP compliant group demonstrated less sleep activity, more wake activity, and expended more energy than the CPAP noncompliant group. This study concluded that CP AP use is a statistically significant factor affecting sleep activity time, wake activity time, and energy expenditure. Regardless of CP AP compliance and length of use, the entire post-CPAP group demonstrated more sleep activity, had less wake activity, and burned fewer calories. From a clinical perspective, the results of this study do not support the use of CP AP as a potential weight loss measure in overweight and obese OSA patients, and emphasize the need for the inclusion of behavioral weight management and weight loss strategies in an at-risk population for comorbid illnesses

Poor sleep quality and progression of gait impairment in an incident Parkinson’s disease cohort

Abnormal sleep may associate with cognitive decline in Parkinson's disease (PD). Furthermore, sleep dysfunction may associate with worse motor outcome. We hypothesised that PD patients with poor quality sleep would have greater progression in gait dysfunction, due to structural and functional overlap in networks subserving sleep and gait regulation. 12 PD patients and 12 age-matched controls completed longitudinal follow-up over 36 months. Poor sleep efficiency and greater sleep fragmentation correlated significantly with progression of step-width variability, a gait characteristic mediated by postural control, providing evidence that poor sleep in PD is associated with a more rapid deterioration in gait

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and &gt;18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (&gt;21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption

Circadian Rhythm Disturbances in Patients with Alzheimer's Disease: A Review

Circadian Rhythm Disturbances (CRDs) affect as many as a quarter of Alzheimer's disease (AD) patients during some stage of their illness. Alterations in the suprachiasmatic nucleus and melatonin secretion are the major factors linked with the cause of CRDs. As a result, the normal physiology of sleep, the biological clock, and core body temperature are affected. This paper systematically discusses some of the causative factors, typical symptoms, and treatment options for CRDs in patients with AD. This paper also emphasizes the implementation of behavioral and environmental therapies before embarking on medications to treat CRDs. Pharmacotherapeutic options are summarized to provide symptomatic benefits for the patient and relieve stress on their families and professional care providers. As of today, there are few studies relative to CRDs in AD. Large randomized trials are warranted to evaluate the effects of treatments such as bright light therapy and engaging activities in the reduction of CRDs in AD patients

Peripheral electrical nerve stimulation and rest-activity rhythm in Alzheimer's disease

Rest-activity rhythm disruption is a prominent clinical feature of Alzheimer's disease (AD). The origin of the altered rest-activity rhythm is believed to be degeneration of the suprachiasmatic nucleus (SCN). In accordance with the 'use it or lose it' hypothesis of Swaab [Neurobiol Aging 1991, 12: 317-324] stimulation of the SCN may prevent age-related loss of neurons and might reactivate nerve cells that are inactive but not lost. Previous studies with relatively small sample sizes have demonstrated positive effects of peripheral electrical nerve stimulation on the rest-activity rhythm in AD patients. The present randomized, placebo-controlled, parallel-group study was meant to replicate prior findings of electrical stimulation in AD in a substantially larger group of AD patients. The experimental group (n = 31) received peripheral electrical nerve stimulation and the placebo group (n = 31) received sham stimulation. Effects of the intervention on the rest-activity rhythm were assessed by using wrist-worn actigraphs. Near-significant findings on the rest-activity rhythm partially support the hypothesis that neuronal stimulation enhances the rest-activity rhythm in AD patients. Interestingly, post-hoc analyses revealed significant treatment effects in a group of patients who were not using acetylcholinesterase inhibitors concomitantly. We conclude that more research is needed before firm general conclusions about the effectiveness of electrical stimulation as a symptomatic treatment in AD can be drawn. In addition, the present post-hoc findings indicate that future studies on non-pharmacological interventions should take medication use into account

Circadian Activity Rhythms for Mothers with an Infant in ICU

Circadian rhythms influence sleep and wakefulness. Circadian activity rhythms (CAR) are altered in individuals with dementia or seasonal affective disorder. To date, studies exploring CAR and sleep in postpartum women are rare. The purpose of this report is to describe relationships between CAR, sleep disturbance, and fatigue among 72 first-time mothers during their second week postpartum while their newborn remain hospitalized in intensive care unit. Seventy-two mothers were included in this secondary data analysis sample from three separate studies. Participants completed the general sleep disturbance scale (GSDS), numerical rating scale for fatigue, and a sleep diary. The objective sleep data included total sleep time (TST), wake after sleep onset (WASO), and CAR determined by the circadian quotient (amplitude/mesor) averaged from at least 48-h of wrist actigraphy monitoring. The TST of mothers who self-reported as poor sleepers was 354 min (SEM = 21.9), with a mean WASO of 19.5% (SEM = 2.8). The overall sleep quality measured by the GSDS was clinically, significantly disrupted (M = 5.5, SD = 1.2). The mean score for morning fatigue was 5.8 (SD = 2.0), indicating moderate fatigue severity. The CAR was 0.62 (SEM = 0.04), indicating poor synchronization. The self-reported good sleepers (GSDS < 3) had better CAR (M = 0.71, SEM = 0.02) than poor sleepers (GSDS > 3) (t[70] = 2.0, p < 0.05). A higher circadian equation was associated with higher TST (r = 0.83, p < 0.001), less WASO (r = −0.50, p < 0.001), lower self-reported sleep disturbance scores (r = −0.35, p = 0.01), and less morning fatigue (r = −0.26). Findings indicate that mothers with a hospitalized infant have both nocturnal sleep problems and disturbed circadian activity rhythms. Factors responsible for these sleep and rhythm disturbances, the adverse effects on mother's physical and mental well-being, and mother–infant relationship require further study