Brendan P Lucey

Washington University in St. Louis | WUSTL , Wash U · Department of Neurology

Objective: In Alzheimer's disease, hyperphosphorylated tau is associated with formation of insoluble paired helical filaments that aggregate as neurofibrillary tau tangles and are associated with neuronal loss and cognitive symptoms. Dual orexin receptor antagonists decrease soluble amyloid-β levels and amyloid plaques in mouse models over-express...

Objective Memory-associated neural circuits produce oscillatory events within single-channel sleep electroencephalography (EEG), including theta bursts (TBs), sleep spindles (SPs) and multiple subtypes of slow waves (SWs). Changes in the temporal “coupling” of these events are proposed to serve as a biomarker for early stages of Alzheimer’s disease...

Background: Sleep disturbances are common after total knee arthroplasty (TKA), yet literature examining sleep and postoperative pain remains sparse. With the use of wearable devices, convenient objective remote sleep monitoring is now possible. We aimed to measure patient sleep following TKA using validated questionnaires and wearable devices to c...

Introduction: Sleep deprivation increases cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels; however, sleep's effect on Aβ and tau in plasma is unknown. Methods: In a cross-over design, CSF Aβ and tau concentrations were measured in five cognitively normal individuals who had blood and CSF collected every 2 hours for 36 hours during sle...

Introduction: We aimed to determine the independent association between sleep quality and Alzheimer's disease (AD) biomarkers, and whether the associations differ with age. Methods: We included 1240 individuals aged ≥50, without dementia from the European Prevention of Alzheimer's Disease v1500.0 dataset. Linear regression was used to examine Pi...

The Institute of Medicine and the National Institute on Aging increasingly understand that knowledge alone is necessary but insufficient to improve healthcare outcomes. Adapting the behaviors of clinicians, patients, and stakeholders to new standards of evidence‐based clinical practice is often significantly delayed. In response, over the past twen...

: There is increasing evidence that patient-reported outcomes following total knee arthroplasty (TKA) are associated with psychosocial factors and pain catastrophizing. Sleep disturbance, pain, and mental health have a complex interaction, which, if unrecognized, can be associated with impaired patient-reported outcomes and dissatisfaction followi...

Introduction High and low sleep duration have been associated with reduced executive function (EF) and episodic memory (EM). However, causal pathways have not been identified. Cardiovascular health may contribute to the relationship between sleep and cognitive aging. Sleep disturbance has been associated with increased hypertension and heart diseas...

Alzheimer’s disease (AD) is a current and growing public health crisis with the worldwide prevalence of AD expected to rise from 46.8 million individuals affected in 2015 to 131.5 million in 2050 [1]. Differentiating AD from other neurodegenerative diseases is frequently difficult on clinical grounds, especially in the earliest stages of disease, a...

Alzheimer disease (AD) pathology accumulates for decades before the onset of cognitive decline. Cognitively normal individuals with biomarker evidence of AD brain pathology (i.e., biomarker+ or preclinical AD) can be differentiated from individuals without AD brain pathology based on naturalistic driving data, such as hard acceleration or braking a...

The kinetics of amyloid beta turnover within human brain is still poorly understood. We previously found a dramatic decline in the turnover of Aβ peptides in normal aging. It was not known if brain interstitial fluid/cerebrospinal fluid (ISF/CSF) fluid exchange, CSF turnover, blood-brain barrier function or proteolysis were affected by aging or the...

Changes in sleep quality are common in Alzheimer’s Disease (AD) and may even play a role in the onset and accumulation of disease. However, in preclinical stages, it is unclear whether sleep quality or sleep disturbance relate to disease pathology after controlling for known covariates and AD risk factors. This study aimed to determine if self‐repo...

Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maint...

Sleep monitoring may provide markers for future Alzheimer’s disease; however, the relationship between sleep and cognitive function in preclinical and early symptomatic Alzheimer’s disease is not well understood. Multiple studies have associated short and long sleep times with future cognitive impairment. Since sleep and the risk of Alzheimer’s dis...

Background Changes in sleep quality are common in Alzheimer’s Disease (AD) and may contribute to the onset and accumulation of disease. However, in preclinical stages, it is unclear whether sleep quality or sleep disturbance relate to disease pathology after controlling for known AD risk factors. This study aimed to determine if self-reported sleep...

Introduction Sleep is a fundamental necessity for health and is commonly disrupted in the perioperative period. Technological improvements leveraging dry electroencephalographic (EEG) sensors have opened the door for large-scale quantitative assessments of sleep in relation to perioperative outcomes. Methods Patients utilized the Dreem (Rhythm, Ne...

The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormaliti...

Introduction: The relative power of slow-delta oscillations in the electroencephalogram (EEG), termed slow-wave activity (SWA), correlates with level of unconsciousness. Acoustic enhancement of SWA has been reported for sleep states, but it remains unknown if pharmacologically induced SWA can be enhanced using sound. Dexmedetomidine is a sedative w...

Introduction Delirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in...

Study Objectives Multiple methods for monitoring sleep-wake activity have identified sleep disturbances as risk factors for Alzheimer disease (AD). In order to identify the level of agreement between different methods, we compared sleep parameters derived from single-channel EEG (scEEG), actigraphy, and sleep diaries in cognitively normal and mildl...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an asymptomatic period of amyloid-β (Aβ) deposition as insoluble extracellular plaque, intracellular tau aggregation, neuronal and synaptic loss, and subsequent cognitive dysfunction and dementia. A growing public health crisis, the worldwide prevalence of AD is e...

Background: Concentrations of soluble amyloid-β (Aβ) oscillate with the sleep-wake cycle in the interstitial fluid of mice and cerebrospinal fluid (CSF) of humans. Further, the concentration of Aβ in CSF increases during sleep deprivation. Stress and disruption of the circadian clock are additional mechanisms hypothesized to increase CSF Aβ levels...

Tau hyperphosphorylation is an early step in tau‐mediated neurodegeneration and is associated with intracellular aggregation of tau as neurofibrillary tangles, neuronal and synaptic loss, and eventual cognitive dysfunction in Alzheimer's disease. Sleep loss increases the cerebrospinal fluid concentration of amyloid‐β and tau. Using mass spectrometr...

Context: Cortisol in blood has a robust circadian rhythm and exerts potent effects on energy balance that are mediated in part by central mechanisms. These interactions involve orexigenic AgRP neurons that are stimulated by glucocorticoids. However, diurnal changes in brain or cerebrospinal fluid (CSF) cortisol and cortisone, which are interconver...

Alzheimer disease (AD) is one of several neurodegenerative diseases characterized by dysregulation, misfolding and accumulation of specific proteins in the CNS. The stable isotope labelling kinetics (SILK) technique is based on generating amino acids labelled with naturally occurring stable (that is, nonradioactive) isotopes of carbon and/or nitrog...

The gold standard for sleep monitoring is attended in-lab polysomnography; however, this method may be cost-prohibitive and inconvenient for patients and research participants. Home sleep testing has gained momentum in the field of sleep medicine due to its convenience and lower cost, as well as being more naturalistic. The accuracy and quality of...

Sleep may protect the brain from AD Two main proteins accumulate in the brain in Alzheimer's disease (AD), β-amyloid (Aβ) and tau. Aβ appears to instigate AD, but tau appears to drive brain damage and cognitive decline. Sleep deprivation is known to increase Aβ acutely and chronically. Now, Holth et al. show that chronic sleep deprivation strongly...

In Alzheimer's disease (AD), deposition of insoluble amyloid- (A) is followed by intracellular aggregation of tau in the neocortex and subsequent neuronal cell loss, synaptic loss, brain atrophy, and cognitive impairment. By the time even the earliest clinical symptoms are detectable, A accumulation is close to reaching its peak and neocor-tical...

In Alzheimer’s disease (AD), deposition of insoluble amyloid-β (Aβ) is followed by intracellular aggregation of tau in the neocortex and subsequent neuronal cell loss, synaptic loss, brain atrophy, and cognitive impairment. By the time even the earliest clinical symptoms are detectable, Aβ accumulation is close to reaching its peak and neocortical...

Sleep disturbances are associated with future risk of Alzheimer's disease. Disrupted sleep increases soluble amyloid-β, suggesting a mechanism for sleep disturbances to increase Alzheimer's disease risk. We tested this response in humans using indwelling lumbar catheters to serially sample cerebrospinal fluid while participants were sleep-deprived,...

To assess stages of Alzheimer's disease (AD) pathogenesis and the efficacy of drugs during clinical trials, there has been immense interest in the field to establish baseline cerebrospinal fluid (CSF) concentrations for potential AD biomarkers such as amyloid-β (Aβ) and tau. Significant within-person variations in CSF Aβ concentrations over time fo...

Introduction Abnormal sleep patterns have been associated with increased risk for cardiovascular disease, diabetes, and neuro-degeneration. This study investigates whether references values obtained from polysomnography (PSG) can be usefully compared to sleep architecture and sleep continuity biomarkers obtained with limited-montage recordings. Me...

Reduced frequency of K-complex waveforms on EEG during non-REM sleep may help to differentiate patients with Alzheimer’s disease from older healthy individuals.

Importance: Recent studies found that the concentration of amyloid-β (Aβ) fluctuates with the sleep-wake cycle. Although the amplitude of this day/night pattern attenuates with age and amyloid deposition, to our knowledge, the association of Aβ kinetics (ie, production, turnover, and clearance) with this oscillation has not been studied. Objectiv...

Recent studies in rodents identified a brain-wide network of perivascular pathways called the glymphatic system that recirculates cerebrospinal fluid (CSF) through the brain parenchyma and clears interstitial solutes, such as β-amyloid (Aβ). Flow decreases through these perivascular pathways with

Sleep fragmentation is characterized by frequent arousals from sleep. It is common in human populations and may occur without shifts in circadian rhythms or decreased overall sleep time. Sleep disturbances, such as from sleep fragmentation, are associated with metabolic and inflammatory changes in

Synaptic dysfunction and neuronal loss are associated with the onset of symptomatic Alzheimer’s disease (AD). Although deposition of β-amyloid (Aβ) in the brain is widely accepted as a key pathogenic event in AD, how Aβ contributes to development of cognitive dysfunction is unclear. Aβ is

Biomarker profiles in early preclinical Alzheimer’s disease may predict progression to Aβ deposition.

Traumatic brain injury damages arousal-producing neurons in the brainstem and hypothalamus.

An accurate home sleep study to assess electroencephalography (EEG)-based sleep stages and EEG power would be advantageous for both clinical and research purposes, such as for longitudinal studies measuring changes in sleep stages over time. The purpose of this study was to compare sleep scoring of a single-channel EEG recorded simultaneously on th...

Sex differences in sleep and circadian rhythms have been reported in both animals and humans. Observed sleep and circadian differences between males and females include the duration of slow wave sleep, endocrine modulation of circadian control, and the timing of clock gene expression rhythms in the

Sleep disturbances in older adults are common and frequently multifactorial. The incidence of insomnia, for instance, increases with age, and the symptoms of insomnia are associated with increased risk of disease and death. Multiple mechanisms have been proposed to account for this increased risk,

Amyloid-β (Aβ) has been investigated as a diagnostic biomarker and therapeutic drug target. Recent studies found that cerebrospinal fluid (CSF) Aβ fluctuates over time, including as a diurnal pattern, and increases in absolute concentration with serial collection. It is currently unknown what effect differences in CSF collection methodology have on...

In a bidirectional relationship, the sleep/wake cycle regulates amyloid-b (Ab) levels and Ab accumulation then disrupts sleep. A quantitative three-way model now suggests that Ab impairs memory via its effect on sleep.

A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation. Seizure activity was evaluated in an adult bang...

We describe a case of absence-like electrographic seizures during NREM sleep in a patient who was taking sodium oxybate, a sodium salt of γ-hydroxybutyric acid (GHB). An overnight full montage electroencephalography (EEG) study revealed numerous frontally predominant rhythmic 1.5-2 Hz sharp waves and spike-wave activity during stage N2 and N3 sleep...

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline that is a growing public health crisis with a prevalence projected to more than double in the next 20 years. Sleep is frequently impaired in individuals with AD. Further, recent studies have linked numerous age-related sleep disturbances such as...

Risk of developing Alzheimer's disease is increased by older age, genetic factors, and several medical risk factors. Studies have also suggested that dietary and lifestyle factors may influence risk, raising the possibility that preventive strategies may be effective. This body of research is incomplete. However, because the most scientifically sup...

Context: In order to characterize diurnal changes in central leptin and its target neuropeptide, proopiomelanocortin (POMC), we measured leptin and POMC in cerebrospinal fluid (CSF) as related to changes in plasma leptin and soluble leptin receptor (sOB-R) levels. CSF and plasma levels of 20 amino acids (AA) were also measured because AA can affec...

Factors other than age and genetics may increase the risk of developing Alzheimer disease (AD). Accumulation of the amyloid-β (Aβ) peptide in the brain seems to initiate a cascade of key events in the pathogenesis of AD. Moreover, evidence is emerging that the sleep-wake cycle directly influences levels of Aβ in the brain. In experimental models, s...

Few studies have examined how patients with chronic HIV infection cope with pain and how pain relates to medication adherence. Pain coping strategies such as catastrophizing are often associated with increased pain and disability and may also influence adherence to medications. The goal of our study is to assess the relationship of catastrophizing...

Henrietta Lacks died in 1951 of an aggressive adenocarcinoma of the cervix. A tissue biopsy obtained for diagnostic evaluation yielded additional tissue for Dr George O. Gey's tissue culture laboratory at Johns Hopkins (Baltimore, Maryland). The cancer cells, now called HeLa cells, grew rapidly in cell culture and became the first human cell line....

Henrietta Lacks died in 1951 of an aggressive adenocarcinoma of the cervix. A tissue biopsy obtained for diagnostic evaluation yielded additional tissue for Dr George O. Gey's tissue culture laboratory at Johns Hopkins (Baltimore, Maryland). The cancer cells, now called HeLa cells, grew rapidly in cell culture and became the first human cell line....

We investigated the feasibility and utilization of conductive plastic electrodes (CPEs) in patients undergoing continuous video-electroencephalographic (EEG) monitoring in the intensive care unit (ICU), and assessed the quality of brain magnetic resonance imaging (MRI) and computed tomography (CT) images obtained during this period. A total of 54 p...

Sir William Osler was the preeminent internist of his time, who also worked as a pathologist for a considerable period during his career. Between 1876 and 1889, he performed nearly 1000 autopsies in Montreal, Quebec, and Philadelphia, Pa. Many authors concluded that Osler stopped performing autopsies once he moved to Baltimore, Md, because the auto...

Sir William Osler was the preeminent internist of his time, who also worked as a pathologist for a considerable period during his career. Between 1876 and 1889, he performed nearly 1000 autopsies in Montreal, Quebec, and Philadelphia, Pa. Many authors concluded that Osler stopped performing autopsies once he moved to Baltimore, Md, because the auto...

Marchiafava-Bignami disease (MBD) is historically reported in middle-aged alcoholic men. We describe the presentation, course and radiological findings of a young non-alcoholic woman who developed encephalopathy and MRI findings consistent with MBD postoperatively. She returned to baseline after vitamin supplementation. We believe it is important t...

A 14-year-old adolescent girl presented with severe congestive heart failure, progressive throughout 3 months. A precordial thrill, machinery-like murmur, and right bundle branch block were noted. Death occurred despite digitalis and diuretic therapy and removal of pleural and ascitic fluid. The autopsy revealed 2 multilocular cystic structures in...

A 14-year-old adolescent girl presented with severe congestive heart failure, progressive throughout 3 months. A precordial thrill, machinery-like murmur, and right bundle branch block were noted. Death occurred despite digitalis and diuretic therapy and removal of pleural and ascitic fluid. The autopsy revealed 2 multilocular cystic structures in...

William H. Welch, MD, and his colleagues performed an autopsy at The Johns Hopkins Hospital in October 1891 on a 38-year-old man and discovered a new bacterium, Bacillus aerogenes capsulatus. During the postmortem examination, gas bubbles were noted within many of the patient's blood vessels. Welch's laboratory personnel determined that a previousl...

William H. Welch, MD, and his colleagues performed an autopsy at The Johns Hopkins Hospital in October 1891 on a 38-year-old man and discovered a new bacterium, Bacillus aerogenes capsulatus. During the postmortem examination, gas bubbles were noted within many of the patient's blood vessels. Welch's laboratory personnel determined that a previousl...

Malignant gliomas are uniformly lethal tumors whose morbidity is mediated in large part by the angiogenic response of the brain to the invading tumor. This profound angiogenic response leads to aggressive tumor invasion and destruction of surrounding brain tissue as well as blood-brain barrier breakdown and life-threatening cerebral edema. To inves...

Objective: To investigate progressive, severe neuromuscular weakness associated with lactic acidosis in some HIV-infected patients after exposure to nucleoside reverse transcriptase inhibitors (NRTI). Methods: HIV-associated neuromuscular weakness syndrome (HANWS) was retrospectively identified and classified based on the level of diagnostic certai...

We report the case of a 23-year-old woman who was abused at the age of 5 months. She suffered from complications frequently associated with shaken baby syndrome, such as hydrocephalus secondary to subarachnoid hemorrhage. The patient underwent a procedure to place a ventriculoperitoneal shunt 3 weeks after her presentation with signs of abuse. The...

We report the case of a 23-year-old woman who was abused at the age of 5 months. She suffered from complications frequently associated with shaken baby syndrome, such as hydrocephalus secondary to subarachnoid hemorrhage. The patient underwent a procedure to place a ventriculoperitoneal shunt 3 weeks after her presentation with signs of abuse. The...