Ariel B. Neikrug

Sleep Disorders in the Older Adult – A Mini-Review

Approximately 50% of older adults complain of difficulty sleeping. Poor sleep results in increased risk of significant morbidity and mortality. The decrements seen in the sleep of the older adult are often due to a decrease in the ability to get needed sleep. However, the decreased ability is less a function of age and more a function of other factors that accompany aging, such as medical and psychiatric illness, increased medication use, advances in the endogenous circadian clock and a higher prevalence of specific sleep disorders. Given the large number of older adults with sleep complaints and sleep disorders, there is a need for health care professionals to have an increased awareness of these sleep disturbances to better enable them to assess and treat these patients. A thorough sleep history (preferably in the presence of their bed partner) is required for a proper diagnosis, and when appropriate, an overnight sleep recording should be done. Treatment of primary sleep problems can improve the quality of life and daytime functioning of older adults. This paper reviews the diagnoses and characteristics of sleep disorders generally found in the older adult. While aimed at the practicing geriatrician, this paper is also of importance for any gerontologist interested in sleep.

Continuous Positive Airway Pressure Improves Sleep and Daytime Sleepiness in Patients with Parkinson Disease and Sleep Apnea

STUDY OBJECTIVES Obstructive sleep apnea (OSA), common in Parkinson disease (PD), contributes to sleep disturbances and daytime sleepiness. We assessed the effect of continuous positive airway pressure (CPAP) on OSA, sleep, and daytime sleepiness in patients with PD. DESIGN This was a randomized placebo-controlled, crossover design. Patients with PD and OSA were randomized into 6 w of therapeutic treatment or 3 w of placebo followed by 3 w of therapeutic treatment. Patients were evaluated by polysomnography (PSG) and multiple sleep latency test (MSLT) pretreatment (baseline), after 3 w, and after 6 w of CPAP treatment. Analyses included mixed models, paired analysis, and within-group analyses comparing 3 w to 6 w of treatment. SETTING Sleep laboratory. PARTICIPANTS Thirty-eight patients with PD (mean age = 67.2 ± 9.2 y; 12 females). INTERVENTION Continuous positive airway pressure. MEASUREMENTS PSG OUTCOME MEASURES: sleep efficiency, %sleep stages (N1, N2, N3, R), arousal index, apnea-hypopnea index (AHI), and % time oxygen saturation < 90% (%time SaO2 < 90%). MSLT outcome measures: mean sleep-onset latency (MSL). RESULTS There were significant group-by-time interactions for AHI (P < 0.001), % time SaO2 < 90% (P = 0.02), %N2 (P = 0.015) and %N3 (P = 0.014). Subjects receiving therapeutic CPAP showed significant decrease in AHI, %time SaO2 < 90%, %N2, and significant increase in %N3 indicating effectiveness of CPAP in the treatment of OSA, improvement in nighttime oxygenation, and in deepening sleep. The paired sample analyses revealed that 3 w of therapeutic treatment resulted in significant decreases in arousal index (t = 3.4, P = 0.002). All improvements after 3 w were maintained at 6 w. Finally, 3 w of therapeutic CPAP also resulted in overall decreases in daytime sleepiness (P = 0.011). CONCLUSIONS Therapeutic continuous positive airway pressure versus placebo was effective in reducing apnea events, improving oxygen saturation, and deepening sleep in patients with Parkinson disease and obstructive sleep apnea. Additionally, arousal index was reduced and effects were maintained at 6 weeks. Finally, 3 weeks of continuous positive airway pressure treatment resulted in reduced daytime sleepiness measured by multiple sleep latency test. These results emphasize the importance of identifying and treating obstructive sleep apnea in patients with Parkinson disease.

Bright Light Therapy Protects Women from Circadian Rhythm Desynchronization During Chemotherapy for Breast Cancer

Circadian rhythms (CRs) are commonly disrupted in women undergoing chemotherapy for breast cancer (BC). Bright light improves and strengthens CRs in other populations. This randomized controlled study examined the effect of morning administration of bright light therapy on CRs in women undergoing chemotherapy for BC. It was hypothesized that women receiving bright light therapy would exhibit more robust rhythms than women exposed to dim light. Thirty-nine women newly diagnosed with BC and scheduled for chemotherapy were randomized into 2 groups: bright white light (BWL) or dim red light (DRL). Women were instructed to use the light box every morning for 30 min during their first 4 cycles of chemotherapy. Wrist actigraphy was recorded at 5 time points: prior to chemotherapy (baseline), Cycle-1 treatment week (C1TW), Cycle-1 recovery week (C1RW), Cycle-4 treatment week (C4TW), and Cycle-4 recovery week (C4RW). There was a Group × Time interaction at C4TW compared to baseline such that the DRL group showed significant deterioration in the mean of the activity rhythm (mesor) and amplitude, whereas the BWL group exhibited a significant increase in both mesor and amplitude. The DRL group also exhibited significant deterioration in overall rhythm robustness at C1TW, C4TW, and C4RW. Women in the BWL group also showed significant decreases in overall rhythm robustness at C1TW and C4TW, but returned to baseline levels at both recovery weeks. The results suggest that morning administration of bright light may protect women from experiencing CR deterioration during chemotherapy.

Effects of Sleep Disorders on the Non-Motor Symptoms of Parkinson Disease

STUDY OBJECTIVES To evaluate the impact of sleep disorders on non-motor symptoms in patients with Parkinson disease (PD). DESIGN This was a cross-sectional study. Patients with PD were evaluated for obstructive sleep apnea (OSA), restless legs syndrome (RLS), periodic limb movement syndrome (PLMS), and REM sleep behavior disorder (RBD). Cognition was assessed with the Montreal Cognitive Assessment and patients completed self-reported questionnaires assessing non-motor symptoms including depressive symptoms, fatigue, sleep complaints, daytime sleepiness, and quality of life. SETTING Sleep laboratory. PARTICIPANTS 86 patients with PD (mean age = 67.4 ± 8.8 years; range: 47-89; 29 women). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Having sleep disorders was a predictor of overall non-motor symptoms in PD (R(2) = 0.33, p < 0.001) while controlling for age, PD severity, and dopaminergic therapy. These analyses revealed that RBD (p = 0.006) and RLS (p = 0.014) were significant predictors of increased non-motor symptoms, but OSA was not. More specifically, having a sleep disorder significantly predicted sleep complaints (ΔR(2) = 0.13, p = 0.006), depressive symptoms (ΔR(2) = 0.01, p = 0.03), fatigue (ΔR(2) = 0.12, p = 0.007), poor quality of life (ΔR(2) = 0.13, p = 0.002), and cognitive decline (ΔR(2) = 0.09, p = 0.036). Additionally, increasing number of sleep disorders (0, 1, or ≥ 2 sleep disorders) was a significant contributor to non-motor symptom impairment (R(2) = 0.28, p < 0.001). CONCLUSION In this study of PD patients, presence of comorbid sleep disorders predicted more non-motor symptoms including increased sleep complaints, more depressive symptoms, lower quality of life, poorer cognition, and more fatigue. RBD and RLS were factors of overall increased non-motor symptoms, but OSA was not.

Diagnostic tools for REM sleep behavior disorder

BACKGROUND Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by loss of muscle atonia during REM sleep that results in motor behaviors. Diagnosis of RBD involves a clinical interview in which history of dream enactment behaviors is elicited and a subsequent overnight polysomnography (PSG) evaluation to assess for REM sleep without atonia (RWA) and/or observe motor behaviors during REM sleep. Therefore, the nature of RBD diagnosis involves both subjective and objective measurements that attempt to qualify and quantify the different diagnostic sub-criteria. OBJECTIVES The primary aim of the current study was to identify and summarize the available clinical measurements that have been used for RBD assessment. METHODS Two major online databases (MEDLINE and PsycInfo) were searched for articles developing, validating, or evaluating psychometric properties of the RBD diagnostic criteria or methods used for diagnosis. Studies of adult subjects (18 years or more) that included sufficient psychometric data for validation were included. RESULTS Fifty-eight studies were found to meet review criteria. The objective measurements for assessment of RBD reviewed included visual electromyographic (EMG) scoring methods, computerized EMG scoring methods, cardiac (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy, actigraphy, behavioral classification and video analysis. Subjective measurements of RBD included interviews and questionnaires. CONCLUSION Sleep history may be sufficient for diagnosis of RBD in some populations. However, PSG is necessary for a definitive diagnosis. EMG scoring methods vary in definition used and there is no single accepted approach to scoring muscle activity. Additional validation studies are required for establishing cutoff scores for the different methods. Questionnaires were shown to be appropriate screening tools, yet further validation in different populations is necessary.

Clinical correlates of periodic limb movements in sleep in Parkinson's disease

OBJECTIVE The aim of the current study was to investigate the frequency of periodic limb movements in sleep (PLMS) in Parkinsons disease (PD) and their impact on nocturnal sleep and daytime functioning. METHODS Forty-five PD patients (mean age 68.5 ± 8.7 years; 32 males) underwent one night of polysomnography (PSG). Clinical assessment and questionnaires evaluating sleep disturbance and quality of life (QoL) were completed. Patients were divided into two groups based on their PLMS index (PLMSI): PLMSI ≥ 15 (PLMS+) and PLMSI <15 (PLMS-). RESULTS There were 26 (57.8%) PD patients in the PLMS+group and 19 (42.2%) patients in the PLMS-group. Subjective assessment revealed an association between PLMS+status and greater PD symptom severity, more subjective sleep disturbance, and decreased QoL. All patients showed poor sleep, and no significant group differences were detected on PSG measures. CONCLUSION We observed that PLMS occurred frequently in PD and increased with more severe PD. Although PLMS did not affect objective sleep, it was associated with increased sleep complaints and reduced QoL. Overall, our findings support the association between PLMS and PD as well as the clinical relevance of sleep disturbances in PD.

Parkinson's disease and REM sleep behavior disorder result in increased non-motor symptoms.

OBJECTIVE Rapid eye movement (REM)-sleep behavior disorder (RBD) is often comorbid with Parkinsons disease (PD). The current study aimed to provide a detailed understanding of the impact of having RBD on multiple non-motor symptoms (NMS) in patients with PD. METHODS A total of 86 participants were evaluated for RBD and assessed for multiple NMS of PD. Principal component analysis was utilized to model multiple measures of NMS in PD, and a multivariate analysis of variance was used to assess the relationship between RBD and the multiple NMS measures. Seven NMS measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall NMS of PD. RESULTS Among the PD patients, 36 were classified as having RBD (objective polysomnography and subjective findings), 26 as not having RBD (neither objective nor subjective findings), and 24 as probably having RBD (either subjective or objective findings). RBD was a significant predictor of increased NMS in PD while controlling for dopaminergic therapy and age (p=0.01). The RBD group reported more NMS of depression (p=0.012), fatigue (p=0.036), overall sleep (p=0.018), and overall NMS (p=0.002). CONCLUSION In PD, RBD is associated with more NMS, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with RBD represent a subtype of PD with different disease progression and phenomenological presentation.

Actigraphy for the Assessment of Sleep Measures in Parkinson's Disease

OBJECTIVES To assess the usefulness of actigraphy for assessment of nighttime sleep measures in patients with Parkinsons disease (PD). DESIGN Participants underwent overnight sleep assessment simultaneously by polysomnography (PSG) and actigraphy. SETTING Overnight sleep study in academic sleep research laboratory. PARTICIPANTS Sixty-one patients (mean age 67.74 ± 8.88 y) with mild to moderate PD. MEASUREMENTS Sleep measures including total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep onset latency (SOL) were calculated independently from data derived from PSG and from actigraphy. Different actigraphy scoring settings were compared. RESULTS No single tested actigraphy scoring setting was optimal for all sleep measures. A customized setting of an activity threshold of 10, with five consecutive immobile minutes for sleep onset, yielded the combination of mean TST, SE, and WASO values that best approximated mean values determined by PSG with differences of 6.05 ± 85.67 min for TST, 1.1 ± 0.641% for SE, and 4.35 ± 59.56 min for WASO. There were significant but moderate correlations between actigraphy and PSG measurements (rs = 0.496, P < 0.001 for TST, rs = 0.384, P = 0.002 for SE, and rs = 0.400, P = 0.001 for WASO) using these settings. Greater disease stage was associated with greater differences between TST (R(2) = 0.099, beta = 0.315, P = 0.018), SE (R(2) = 0.107, beta = 0.327, P = 0.014), and WASO (R(2) = 0.094, beta = 0.307, P = 0.021) values derived by actigraphy and PSG explaining some of the variability. Using a setting of 10 immobile min for sleep onset yielded a mean SOL that was within 1 min of that estimated by PSG. However SOL values determined by actigraphy and PSG were not significantly correlated at any tested setting. CONCLUSIONS Our results suggest that actigraphy may be useful for measurement of mean TST, SE, and WASO values in groups of patients with mild to moderate Parkinsons disease. However, there is a significant degree of variability in accuracy among individual patients. The importance of determining optimal scoring parameters for each population studied is underscored.

Fatigue and Circadian Activity Rhythms in Breast Cancer Patients Before and After Chemotherapy: A Controlled Study

Background: Breast cancer (BC) patients often experience cancer-related fatigue (CRF) before, during, and after their chemotherapy. Circadian rhythms are 24-hour cycles of behavior and physiology that are generated by internal pacemakers and entrained by zeitgebers (e.g., light). A few studies have suggested a relationship between fatigue and circadian rhythms in some clinical populations. Methods: One hundred and forty-eight women diagnosed with stage I–III breast cancer and scheduled to receive at least four cycles of adjuvant or neoadjuvant chemotherapy, and 61 controls (cancer-free healthy women) participated in this study. Data were collected before (Baseline) and after four cycles of chemotherapy (Cycle-4). Fatigue was assessed with the Short Form of Multidimensional Fatigue Symptom Inventory (MFSI–SF); circadian activity rhythm (CAR) was recorded with wrist actigraphy (six parameters included: amplitude, acrophase, mesor, up-mesor, down-mesor and F-statistic). A mixed model analysis was used to examine changes in fatigue and CAR parameters compared to controls, and to examine the longitudinal relationship between fatigue and CAR parameters in BC patients. Results: More severe CRF (total and subscale scores) and disrupted CAR (amplitude, mesor and F-statistic) were observed in BC patients compared to controls at both Baseline and Cycle-4 (all ps < 0.05); BC patients also experienced more fatigue and decreased amplitude and mesor, as well as delayed up-mesor time at Cycle-4 compared to Baseline (all ps < 0.05). The increased total MFSI–SF scores were significantly associated with decreased amplitude, mesor and F-statistic (all ps < 0.006). Conclusion: CRF exists and CAR is disrupted even before the start of chemotherapy. The significant relationship between CRF and CAR indicate possible underlying connections. Re-entraining the disturbed CAR using effective interventions such as bright light therapy might also improve CRF.

Relationships between clinical characteristics and nocturnal cardiac autonomic activity in Parkinson's disease

BACKGROUND The aim of the present study was to explore the association between Parkinsons disease (PD) clinical characteristics and cardiac autonomic control across sleep stages. METHODS Frequency-domain heart rate variability (HRV) measures were estimated in 18 PD patients undergoing a night of polysomnography. RESULTS Significant relationships were found between PD severity and nocturnal HRV indices. The associations were restricted to rapid eye movement (R) sleep. CONCLUSIONS The progressive nocturnal cardiac autonomic impairment occurring with more severe PD can be subclinical emerging only during conditions requiring active modulation of physiological functions such as R-sleep.