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Lifestyle interventions to increase exercise and improve diet have been the focus of recent clinical trials to potentially prevent Alzheimer's disease (AD). However, despite the strong links between sleep disruptions, cognitive decline, and AD, sleep enhancement has yet to be targeted as a lifestyle intervention to prevent AD. A recent meta-analysis suggests that approximately 15% of AD may be prevented by an efficacious intervention aimed to reduce sleep disturbances and sleep disorders. Chronic insomnia is the most frequent sleep disorder occurring in at least 40% of older adults. Individuals with insomnia are more likely to be diagnosed with Alzheimer's Disease (AD) and demonstrate decline in cognitive function at long-term follow-up. AD is characterized by the accumulation of amyloid-β (Aβ) plaques and tau tangles in the brain, and growing evidence shows impaired sleep contributes to the accumulation of Aβ. An intervention aimed at improving insomnia may be a critical opportunity for primary prevention to slow cognitive decline and potentially delay the onset of AD. Cognitive behavioral therapy for insomnia (CBT-I) is an efficacious treatment for insomnia, but the use of CBT-I to improve cognitive function and potentially reduce the rate of Aβ accumulation has never been examined. Therefore, the objective of the proposed study is to examine the efficacy of CBT-I on improving cognitive function in older adults with symptoms of insomnia. An exploratory aim is to assess the effect of CBT-I on rate of Aβ accumulation., (Copyright © 2020. Published by Elsevier Inc.)

Background: Implantable hypoglossal nerve upper airway stimulation (HNS) is a novel strategy approved by the US Food and Drug Administration for the management of moderate-to-severe obstructive sleep apnea (OSA) in patients with continuous positive airway pressure therapy intolerance or failure. Because of the proximity of a cardiac implantable electronic device (CIED) to this stimulator, interaction between these devices is theoretically possible., Objective: The purpose of this study was to assess interactions between an implantable HNS device and a CIED., Methods: We retrospectively analyzed 14 ad hoc patients with continuous positive airway pressure-intolerant, moderate-to-severe OSA and pre-existing transvenous CIEDs undergoing HNS implantation (Inspire II, Inspire Medical Systems). We assessed these devices for their pre and postimplant OSA outcomes and for possible device-device interaction. All patients were followed up for 1 year., Results: Of the 14 patients, 9 had a pacemaker (8 dual-chamber, 1 single-chamber), 4 had an implantable cardioverter-defibrillator (2 dual-chamber, 1 single-chamber), and 1 had a cardiac resynchronization therapy device. All the HNS devices were implanted on the opposite side of the CIED. All CIEDs were programmed bipolar. HNS were programmed either unipolar or bipolar. During implant, intraoperative testing was performed to confirm that bipolar and unipolar HNS stimulation did not impact CIED sensing. During the follow-up period, no oversensing episodes were noted on the CIEDs., Conclusion: In this early experience, simultaneous use of a novel hypoglossal nerve upper airway stimulation device with transvenous CIEDs seems to be safe, effective, and without any device-device interactions., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Thrombolysis remains the first-line therapy in a substantial proportion of patients presenting with ST elevation myocardial infarction. The optimal treatment for patients in whom there is failure of reperfusion following thrombolysis is unclear. The Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis (REACT) trial demonstrated, in 427 randomly assigned patients with failed reperfusion following thrombolysis, that event-free survival rates were significantly improved with rescue angioplasty compared with either repeat thrombolysis or conservative treatment. However, the safety and efficacy of rescue angioplasty among older patients remains uncertain., Methods and Results: We aimed to determine whether rescue angioplasty was safe and effective in an older population, by evaluating the primary and secondary clinical outcomes among the 105 patients >or=70 years of age in the REACT trial. We observed an increased overall 6-month event rate among older patients. The relative benefit of rescue angioplasty versus repeat thrombolysis or conservative treatment was maintained, and the absolute benefit actually increased in this older age group compared with the study population as a whole. There was no adverse impact of advanced age on bleeding complications. Repeat thrombolysis was no more effective than conservative therapy., Conclusions: Rescue angioplasty is the preferred management strategy for failed thrombolysis, even for patients >or=70 years of age.

In the present study, young (5-month-old (mo)) and aged (24 mo) adult male Fischer-344 (F344) rats were assigned to experimental groups based upon their performance of a reference memory task in the Morris water maze and reactivity to a novel palatable taste in a gustatory neophobia task. Levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) were assayed via high performance liquid chromatography (HPLC) in brain regions associated with the locus coeruleus (LC)-hippocampus-cortex system and A1/A2-hypothalamic system. Binding of ligands specific for alpha-1, alpha-2, beta-1, and beta-2 receptors was assessed in hippocampus and cortex with receptor autoradiography. Impaired acquisition and retention of the water maze task and gustatory neophobia in aged rats was primarily associated with decreased NE activity in cingulate cortex (CC) as indicated by a significant reduction in the MHPG/NE ratio coupled with increased NE content. No significant changes in adrenergic receptor binding were detected in any region sampled. The results suggest that an aging-related reduction in cortical NE neurotransmission is associated with the expression of increased neophobia and deficits in spatial learning and memory performance occurring with advanced age in rats.

In susceptible strains of mice, the LP-BM5 mixture of murine retroviruses induces the fatal immunodeficiency disease known as murine acquired immunodeficiency syndrome (murine AIDS or MAIDS). We have previously reported that murine AIDS produces a profound depletion of splenic norepinephrine (NE). Here, we demonstrate that NE depletion is limited to the spleen, a major site affected by LP-BM5 infection. NE depletion in the spleen is first observed at two weeks following LP-BM5 inoculation, concurrent with the onset of splenomegaly, and continues through 12 weeks post-infection. Neuroanatomical studies revealed that the reduction in NE is due to destruction of splenic sympathetic nerve fibers. Administration of the NE reuptake blocker desipramine did not prevent LP-BM5-induced NE depletion, suggesting that destruction is not caused by excess release and reuptake of NE. Elucidating the mechanism of MAIDS-induced sympathetic nerve destruction may provide insight into autonomic and peripheral neuropathies reported in people with AIDS.

Numerous studies have shown that alterations in sympathetic nervous system (SNS) function produced by beta-adrenergic receptor blockade or chemical sympathectomy can produce changes in T and B lymphocyte function and both innate and acquired immune responses. However, fewer studies have investigated changes in immune response following SNS alterations in animal models of disease. We tested whether blocking SNS activity using 6-OHDA or the beta-receptor antagonist nadolol alters the typical pattern in production of T helper 1 (Th1) and Th2 cytokines seen in cultures of spleen cells from C57BL/6 mice infected with murine AIDS (MAIDS). We found that neither method of sympathetic blockade affected cytokine response to MAIDS. We also found that the norepinephrine concentration and content of the spleen were reduced dramatically by the MAIDS infection itself at 3 and 6 weeks after LP-BM5 inoculation. This finding has not been previously reported in mice with MAIDS and suggests that the viral infection itself produces a functional sympathectomy in the spleen, a target of that infection., (Copyright 2001 Elsevier Science (USA).)