Eszopiclone for late-life insomnia

Insomnia, the most common sleep disturbance in later life, affects 20%–50% of older adults. Eszopiclone, a short-acting nonbenzodiazepine hypnotic agent developed for the treatment of insomnia, has been available in Europe since 1992 and in the US since 2005. Although not yet evaluated for transient insomnia in older adults, eszopiclone has been shown to be safe and efficacious for short-term treatment (2 weeks) of chronic, primary insomnia in older adults (64–91 years). Clinical studies in younger adults (mean = 44 years) have shown eszopiclone can be used for 6–12 months without evidence of problems. Because the oldest participant in these longer-term trials was 69, it not known whether eszopiclone is effective for older adults [particularly the old old (75–84 years) and oldest old (85+)] when used over longer periods. This is unfortunate, because older individuals frequently suffer from chronic insomnia. Cognitive-behavioral therapy for insomnia, which effectively targets the behavioral factors that maintain chronic insomnia, represents an attractive treatment alternative or adjuvant to eszopiclone for older adults. To date, no studies have compared eszopiclone to other hypnotic medications or to nonpharmacological interventions, such as cognitive-behavioral therapy for insomnia, in older adults. All of the clinical trials reported herein were funded by Sepracor. This paper provides an overview of the literature on eszopiclone with special emphasis on its use for the treatment of late-life insomnia. Specific topics covered include pharmacology, pharmacodynamics, pharmacokinetics, clinical trial data, adverse events, drug interactions, tolerance/dependence, and economics/cost considerations for older adults

APOE ε4 as a Predictor of Tauopathies Independent of β-Amyloid

Background: Due to the failure of clinical trials that target amyloid β and findings that suggest tau’s role in Alzheimer’s Disease (AD) atrophy and cognitive decline, the investigation of tau-pathology in AD is needed. While studies have investigated the effect of APOE ε4 on tau-pathology in mouse models, few have examined the relationship in humans, as well as tau’s role on cognitive decline as a mechanism independent of amyloid β deposition. The aim will be to examine the roles of tau in AD, as an independent pathway. Method: Utilizing the National Alzheimer’s Coordinating Center (NACC) database, our sample included those determined with AD, as defined by NACC derived variables. Among participants (n= 5391,Mage= 73, SD=10.5) ε4 carriers accounted for 42%. A separate longitudinal sample (n=108, Mage= 70, SD=9.80) was used to determine cognitive decline as measured by the MoCA. Result: The ANCOVA showed a significant effect of APOE carrier status on neurofibrillary tangles after controlling for neuritic plaques, F(1,5390) = 5643.617, p\u3c.001, partial η2=.512 and separately, after controlling for Thal amyloid phases, F(1,2632) =4809.032, p\u3c.001, partial η2=.646. The regression model showed covariates including sex, race, ethnicity, age, education, and language did not contribute significantly to the model, F(6,102) =2.051, p\u3c=0.66 and accounted for 10.8% of the variation on MoCA scores. Introducing APOE carrier status explained 16.5% of the variation of MoCA and was significant in change, F(1,101) =6.891, p=.010. While addition of all neuropathies explained 32.9% of the model, F(3,98) =7.979, p\u3c.001, post hoc T-tests revealed that only neurofibrillary tangles had a significant effect on cognitive decline, demonstrating a negative relationship. Conclusion: These results indicate that the neuropathological effects of APOE ε4 are demonstrated with or without amyloid β deposition, suggesting that apoE may act through tau-pathways independently. Additionally, while the relationship between APOE ε4 and neuropathology predicts cognitive decline, NFT is the primary driver of cognitive decline in Alzheimer\u27s Disease, while amyloid β deposition has no significant effect

Night-To-Night Sleep Variability in Older Adults with Chronic Insomnia: A Randomized Controlled Trial of Brief Behavioral Therapy for Insomnia

Introduction: Night-to-night variability in sleep is a clinical feature in understanding and treating insomnia in older adults. The present study examined changes in sleep variability in the course of a brief behavioral treatment for insomnia (BBT-I) in older adults who had chronic insomnia. Additionally, the present study examined the mediating mechanisms underlying reductions of sleep variability and the moderating effects of baseline sleep variability on treatment responsiveness. Methods: Sixty-two elderly participants were randomly assigned to either BBT-I or waitlist control (WLC). Sleep was assessed by sleep diaries and actigraphy from baseline to posttreatment and at 3-month follow-up. Mixed models were used to examine changes in sleep variability (within-person standard deviations of weekly sleep parameters) and the hypothesized mediation and moderation effects. Results: Variability in diary-assessed sleep onset latency (SOL) and actigraphy-assessed total sleep time (TST) significantly decreased in BBT-I compared to WLC (Pseudo R2=.12, .27; p=.018, .008). These effects were mediated by reductions in bedtime and wake time variability and time in bed. Significant time by group by baseline sleep variability interactions on sleep outcomes indicated that participants who had higher baseline sleep variability were more responsive to BBT-I; their actigraphy-assessed TST, SOL, and sleep efficiency improved to a greater degree (Pseudo R2=.15-.66; p\u3c.001-.044). Conclusion: BBT-I is effective in reducing sleep variability in older adults who have chronic insomnia. Increased consistency in bedtime and wake time and decreased time in bed mediate reductions of sleep variability. Baseline sleep variability may serve as a marker of greater treatment responsiveness to BBT-I. Support (If Any): The project described was supported by Award Number AG024459 (Christina S. McCrae, Ph.D., PI) from the National Institute on Aging (NIA). Additional support was provided by an Institutional Training Grant Award Number AG020499 (Michael Marsiske, PhD, Director) from the NIA