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2.
Atherosclerosis ; : 117481, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38480058

ABSTRACT

BACKGROUND AND AIMS: Atherosclerotic plaque fluorine-18 sodium fluoride (18F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18F-NaF uptake. METHODS: Subjects with high CV risk but without CV events underwent 18F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20 mg/daily for six months, and re-evaluated by 18F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation. RESULTS: Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7 ± 18.7% for ASCVD systems. After six months of rosuvastatin treatment (n = 34), low-density lipoprotein cholesterol lowered from 133.6 ± 33.8 to 58.8 ± 20.7 mg dL-1 (60% relative reduction, p < 0.01). There was a significant 19% reduction in maximum plaque 18F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p < 0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p = 0.003). CONCLUSION: In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18F-NaF uptake was significantly reduced after six months of high-intensity statin.

3.
Neurol Clin Pract ; 14(1): e200225, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38173542

ABSTRACT

Background and Objectives: Patterns of electrical activity in the brain (EEG) during sleep are sensitive to various health conditions even at subclinical stages. The objective of this study was to estimate sleep EEG-predicted incidence of future neurologic, cardiovascular, psychiatric, and mortality outcomes. Methods: This is a retrospective cohort study with 2 data sets. The Massachusetts General Hospital (MGH) sleep data set is a clinic-based cohort, used for model development. The Sleep Heart Health Study (SHHS) is a community-based cohort, used as the external validation cohort. Exposure is good, average, or poor sleep defined by quartiles of sleep EEG-predicted risk. The outcomes include ischemic stroke, intracranial hemorrhage, mild cognitive impairment, dementia, atrial fibrillation, myocardial infarction, type 2 diabetes, hypertension, bipolar disorder, depression, and mortality. Diagnoses were based on diagnosis codes, brain imaging reports, medications, cognitive scores, and hospital records. We used the Cox survival model with death as the competing risk. Results: There were 8673 participants from MGH and 5650 from SHHS. For all outcomes, the model-predicted 10-year risk was within the 95% confidence interval of the ground truth, indicating good prediction performance. When comparing participants with poor, average, and good sleep, except for atrial fibrillation, all other 10-year risk ratios were significant. The model-predicted 10-year risk ratio closely matched the observed event rate in the external validation cohort. Discussion: The incidence of health outcomes can be predicted by brain activity during sleep. The findings strengthen the concept of sleep as an accessible biological window into unfavorable brain and general health outcomes.

4.
Sci Rep ; 13(1): 11448, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37454163

ABSTRACT

Sleep electroencephalogram (EEG) signals likely encode brain health information that may identify individuals at high risk for age-related brain diseases. Here, we evaluate the correlation of a previously proposed brain age biomarker, the "brain age index" (BAI), with cognitive test scores and use machine learning to develop and validate a series of new sleep EEG-based indices, termed "sleep cognitive indices" (SCIs), that are directly optimized to correlate with specific cognitive scores. Three overarching cognitive processes were examined: total, fluid (a measure of cognitive processes involved in reasoning-based problem solving and susceptible to aging and neuropathology), and crystallized cognition (a measure of cognitive processes involved in applying acquired knowledge toward problem-solving). We show that SCI decoded information about total cognition (Pearson's r = 0.37) and fluid cognition (Pearson's r = 0.56), while BAI correlated only with crystallized cognition (Pearson's r = - 0.25). Overall, these sleep EEG-derived biomarkers may provide accessible and clinically meaningful indicators of neurocognitive health.


Subject(s)
Brain Waves , Sleep , Humans , Cognition , Problem Solving , Brain , Electroencephalography , Biomarkers
5.
Chronobiol Int ; 40(6): 759-768, 2023 06 03.
Article in English | MEDLINE | ID: mdl-37144470

ABSTRACT

Intensive care units (ICUs) may disrupt sleep. Quantitative ICU studies of concurrent and continuous sound and light levels and timings remain sparse in part due to the lack of ICU equipment that monitors sound and light. Here, we describe sound and light levels across three adult ICUs in a large urban United States tertiary care hospital using a novel sensor. The novel sound and light sensor is composed of a Gravity Sound Level Meter for sound level measurements and an Adafruit TSL2561 digital luminosity sensor for light levels. Sound and light levels were continuously monitored in the room of 136 patients (mean age = 67.0 (8.7) years, 44.9% female) enrolled in the Investigation of Sleep in the Intensive Care Unit study (ICU-SLEEP; Clinicaltrials.gov: #NCT03355053), at the Massachusetts General Hospital. The hours of available sound and light data ranged from 24.0 to 72.2 hours. Average sound and light levels oscillated throughout the day and night. On average, the loudest hour was 17:00 and the quietest hour was 02:00. Average light levels were brightest at 09:00 and dimmest at 04:00. For all participants, average nightly sound levels exceeded the WHO guideline of < 35 decibels. Similarly, mean nightly light levels varied across participants (minimum: 1.00 lux, maximum: 577.05 lux). Sound and light events were more frequent between 08:00 and 20:00 than between 20:00 and 08:00 and were largely similar on weekdays and weekend days. Peaks in distinct alarm frequencies (Alarm 1) occurred at 01:00, 06:00, and at 20:00. Alarms at other frequencies (Alarm 2) were relatively consistent throughout the day and night, with a small peak at 20:00. In conclusion, we present a sound and light data collection method and results from a cohort of critically ill patients, demonstrating excess sound and light levels across multiple ICUs in a large tertiary care hospital in the United States. ClinicalTrials.gov, #NCT03355053. Registered 28 November 2017, https://clinicaltrials.gov/ct2/show/NCT03355053.


Subject(s)
Circadian Rhythm , Intensive Care Units , Adult , Aged , Female , Humans , Male , Middle Aged , Hospitals, Urban , Noise , Sleep , United States
6.
Front Netw Physiol ; 3: 1120390, 2023.
Article in English | MEDLINE | ID: mdl-36926545

ABSTRACT

Introduction: To measure sleep in the intensive care unit (ICU), full polysomnography is impractical, while activity monitoring and subjective assessments are severely confounded. However, sleep is an intensely networked state, and reflected in numerous signals. Here, we explore the feasibility of estimating conventional sleep indices in the ICU with heart rate variability (HRV) and respiration signals using artificial intelligence methods Methods: We used deep learning models to stage sleep with HRV (through electrocardiogram) and respiratory effort (through a wearable belt) signals in critically ill adult patients admitted to surgical and medical ICUs, and in age and sex-matched sleep laboratory patients Results: We studied 102 adult patients in the ICU across multiple days and nights, and 220 patients in a clinical sleep laboratory. We found that sleep stages predicted by HRV- and breathing-based models showed agreement in 60% of the ICU data and in 81% of the sleep laboratory data. In the ICU, deep NREM (N2 + N3) proportion of total sleep duration was reduced (ICU 39%, sleep laboratory 57%, p < 0.01), REM proportion showed heavy-tailed distribution, and the number of wake transitions per hour of sleep (median 3.6) was comparable to sleep laboratory patients with sleep-disordered breathing (median 3.9). Sleep in the ICU was also fragmented, with 38% of sleep occurring during daytime hours. Finally, patients in the ICU showed faster and less variable breathing patterns compared to sleep laboratory patients Conclusion: The cardiovascular and respiratory networks encode sleep state information, which, together with artificial intelligence methods, can be utilized to measure sleep state in the ICU.

7.
Neurobiol Aging ; 124: 60-70, 2023 04.
Article in English | MEDLINE | ID: mdl-36739622

ABSTRACT

Both sleep and wake encephalograms (EEG) change over the lifespan. While prior studies have characterized age-related changes in the EEG, the datasets span a particular age group, or focused on sleep and wake macrostructure rather than the microstructure. Here, we present sex-stratified data from 3372 community-based or clinic-based otherwise neurologically and psychiatrically healthy participants ranging from 11 days to 80 years of age. We estimate age norms for key sleep and wake EEG parameters including absolute and relative powers in delta, theta, alpha, and sigma bands, as well as sleep spindle density, amplitude, duration, and frequency. To illustrate the potential use of the reference measures developed herein, we compare them to sleep EEG recordings from age-matched participants with Alzheimer's disease, severe sleep apnea, depression, osteoarthritis, and osteoporosis. Although the partially clinical nature of the datasets may bias the findings towards less normal and hence may underestimate pathology in practice, age-based EEG reference values enable objective screening of deviations from healthy aging among individuals with a variety of disorders that affect brain health.


Subject(s)
Alzheimer Disease , Sleep Wake Disorders , Humans , Longevity , Sleep , Electroencephalography , Brain
8.
Sensors (Basel) ; 23(2)2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36679683

ABSTRACT

The economic and environmental sustainability of extensive livestock production systems requires the optimisation of soil management, pasture production and animal grazing. Soil compaction is generally viewed as an indicator of soil degradation processes and a determinant factor in crop productivity. In the Montado silvopastoral ecosystem, characteristic of the Iberian Peninsula, animal trampling is mentioned as a variable to consider in soil compaction. This study aims: (i) to assess the spatial variation in the compaction profile of the 0-0.30 m deep soil layer over several years; (ii) to evaluate the effect of animal trampling on soil compaction; and (iii) to demonstrate the utility of combining various technological tools for sensing and mapping indicators of soil characteristics (Cone Index, CI; and apparent electrical conductivity, ECa), of pastures' vegetative vigour (Normalised Difference Vegetation Index, NDVI) and of cows' grazing zones (Global Positioning Systems, GPS collars). The significant correlation between CI, soil moisture content (SMC) and ECa and between ECa and soil clay content shows the potential of using these expedient tools provided by the development of Precision Agriculture. The compaction resulting from animal trampling was significant outside the tree canopy (OTC) in the four evaluated dates and in the three soil layers considered (0-0.10 m; 0.10-0.20 m; 0.20-0.30 m). However, under the tree canopy (UTC), the effect of animal trampling was significant only in the 0-0.10 m soil layer and in three of the four dates, with a tendency for a greater CI at greater depths (0.10-0.30 m), in zones with a lower animal presence. These results suggest that this could be a dynamic process, with recovery cycles in the face of grazing management, seasonal fluctuations in soil moisture or spatial variation in specific soil characteristics (namely clay contents). The NDVI shows potential for monitoring the effect of livestock trampling during the peak spring production phase, with greater vigour in areas with less animal trampling. These results provide good perspectives for future studies that allow the calibration and validation of these tools to support the decision-making process of the agricultural manager.


Subject(s)
Ecosystem , Soil , Female , Animals , Cattle , Clay , Agriculture , Livestock , Trees
9.
Sleep Breath ; 27(3): 1013-1026, 2023 06.
Article in English | MEDLINE | ID: mdl-35971023

ABSTRACT

PURPOSE: Sleep-disordered breathing may be induced by, exacerbate, or complicate recovery from critical illness. Disordered breathing during sleep, which itself is often fragmented, can go unrecognized in the intensive care unit (ICU). The objective of this study was to investigate the prevalence, severity, and risk factors of sleep-disordered breathing in ICU patients using a single respiratory belt and oxygen saturation signals. METHODS: Patients in three ICUs at Massachusetts General Hospital wore a thoracic respiratory effort belt as part of a clinical trial for up to 7 days and nights. Using a previously developed machine learning algorithm, we processed respiratory and oximetry signals to measure the 3% apnea-hypopnea index (AHI) and estimate AH-specific hypoxic burden and periodic breathing. We trained models to predict AHI categories for 12-h segments from risk factors, including admission variables and bio-signals data, available at the start of these segments. RESULTS: Of 129 patients, 68% had an AHI ≥ 5; 40% an AHI > 15, and 19% had an AHI > 30 while critically ill. Median [interquartile range] hypoxic burden was 2.8 [0.5, 9.8] at night and 4.2 [1.0, 13.7] %min/h during the day. Of patients with AHI ≥ 5, 26% had periodic breathing. Performance of predicting AHI-categories from risk factors was poor. CONCLUSIONS: Sleep-disordered breathing and sleep apnea events while in the ICU are common and are associated with substantial burden of hypoxia and periodic breathing. Detection is feasible using limited bio-signals, such as respiratory effort and SpO2 signals, while risk factors were insufficient to predict AHI severity.


Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/diagnosis , Cross-Sectional Studies , Prevalence , Polysomnography , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/epidemiology , Hypoxia/complications , Intensive Care Units
10.
Crit Care Explor ; 4(1): e0611, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35072078

ABSTRACT

To develop a physiologic grading system for the severity of acute encephalopathy manifesting as delirium or coma, based on EEG, and to investigate its association with clinical outcomes. DESIGN: This prospective, single-center, observational cohort study was conducted from August 2015 to December 2016 and October 2018 to December 2019. SETTING: Academic medical center, all inpatient wards. PATIENTS/SUBJECTS: Adult inpatients undergoing a clinical EEG recording; excluded if deaf, severely aphasic, developmentally delayed, non-English speaking (if noncomatose), or if goals of care focused primarily on comfort measures. Four-hundred six subjects were assessed; two were excluded due to technical EEG difficulties. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A machine learning model, with visually coded EEG features as inputs, was developed to produce scores that correlate with behavioral assessments of delirium severity (Confusion Assessment Method-Severity [CAM-S] Long Form [LF] scores) or coma; evaluated using Spearman R correlation; area under the receiver operating characteristic curve (AUC); and calibration curves. Associations of Visual EEG Confusion Assessment Method Severity (VE-CAM-S) were measured for three outcomes: functional status at discharge (via Glasgow Outcome Score [GOS]), inhospital mortality, and 3-month mortality. Four-hundred four subjects were analyzed (mean [sd] age, 59.8 yr [17.6 yr]; 232 [57%] male; 320 [79%] White; 339 [84%] non-Hispanic); 132 (33%) without delirium or coma, 143 (35%) with delirium, and 129 (32%) with coma. VE-CAM-S scores correlated strongly with CAM-S scores (Spearman correlation 0.67 [0.62-0.73]; p < 0.001) and showed excellent discrimination between levels of delirium (CAM-S LF = 0 vs ≥ 4, AUC 0.85 [0.78-0.92], calibration slope of 1.04 [0.87-1.19] for CAM-S LF ≤ 4 vs ≥ 5). VE-CAM-S scores were strongly associated with important clinical outcomes including inhospital mortality (AUC 0.79 [0.72-0.84]), 3-month mortality (AUC 0.78 [0.71-0.83]), and GOS at discharge (0.76 [0.69-0.82]). CONCLUSIONS: VE-CAM-S is a physiologic grading scale for the severity of symptoms in the setting of delirium and coma, based on visually assessed electroencephalography features. VE-CAM-S scores are strongly associated with clinical outcomes.

11.
Sleep Breath ; 26(3): 1033-1044, 2022 09.
Article in English | MEDLINE | ID: mdl-34409545

ABSTRACT

OBJECTIVE: Sleep-related respiratory abnormalities are typically detected using polysomnography. There is a need in general medicine and critical care for a more convenient method to detect sleep apnea automatically from a simple, easy-to-wear device. The objective was to detect abnormal respiration and estimate the Apnea-Hypopnea Index (AHI) automatically with a wearable respiratory device with and without SpO2 signals using a large (n = 412) dataset serving as ground truth. DESIGN: Simultaneously recorded polysomnography (PSG) and wearable respiratory effort data were used to train and evaluate models in a cross-validation fashion. Time domain and complexity features were extracted, important features were identified, and a random forest model was employed to detect events and predict AHI. Four models were trained: one each using the respiratory features only, a feature from the SpO2 (%)-signal only, and two additional models that use the respiratory features and the SpO2 (%) feature, one allowing a time lag of 30 s between the two signals. RESULTS: Event-based classification resulted in areas under the receiver operating characteristic curves of 0.94, 0.86, and 0.82, and areas under the precision-recall curves of 0.48, 0.32, and 0.51 for the models using respiration and SpO2, respiration-only, and SpO2-only, respectively. Correlation between expert-labelled and predicted AHI was 0.96, 0.78, and 0.93, respectively. CONCLUSIONS: A wearable respiratory effort signal with or without SpO2 signal predicted AHI accurately, and best performance was achieved with using both signals.


Subject(s)
Sleep Apnea Syndromes , Wearable Electronic Devices , Humans , Oxygen , Oxygen Saturation , Polysomnography , Respiratory Rate
12.
Crit Care Med ; 50(1): e11-e19, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34582420

ABSTRACT

OBJECTIVES: Delirium is a common and frequently underdiagnosed complication in acutely hospitalized patients, and its severity is associated with worse clinical outcomes. We propose a physiologically based method to quantify delirium severity as a tool that can help close this diagnostic gap: the Electroencephalographic Confusion Assessment Method Severity Score (E-CAM-S). DESIGN: Retrospective cohort study. SETTING: Single-center tertiary academic medical center. PATIENTS: Three-hundred seventy-three adult patients undergoing electroencephalography to evaluate altered mental status between August 2015 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed the E-CAM-S based on a learning-to-rank machine learning model of forehead electroencephalography signals. Clinical delirium severity was assessed using the Confusion Assessment Method Severity (CAM-S). We compared associations of E-CAM-S and CAM-S with hospital length of stay and inhospital mortality. E-CAM-S correlated with clinical CAM-S (R = 0.67; p < 0.0001). For the overall cohort, E-CAM-S and CAM-S were similar in their strength of association with hospital length of stay (correlation = 0.31 vs 0.41, respectively; p = 0.082) and inhospital mortality (area under the curve = 0.77 vs 0.81; p = 0.310). Even when restricted to noncomatose patients, E-CAM-S remained statistically similar to CAM-S in its association with length of stay (correlation = 0.37 vs 0.42, respectively; p = 0.188) and inhospital mortality (area under the curve = 0.83 vs 0.74; p = 0.112). In addition to previously appreciated spectral features, the machine learning framework identified variability in multiple measures over time as important features in electroencephalography-based prediction of delirium severity. CONCLUSIONS: The E-CAM-S is an automated, physiologic measure of delirium severity that predicts clinical outcomes with a level of performance comparable to conventional interview-based clinical assessment.


Subject(s)
Confusion/diagnosis , Delirium/diagnosis , Electroencephalography/methods , Image Processing, Computer-Assisted/methods , Machine Learning , Academic Medical Centers/statistics & numerical data , Adult , Aged , Comorbidity , Female , Hospital Mortality/trends , Hospitals/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Patient Acuity , Prognosis , Retrospective Studies , Severity of Illness Index
13.
PLoS One ; 16(12): e0259840, 2021.
Article in English | MEDLINE | ID: mdl-34855749

ABSTRACT

BACKGROUND: We investigated the effect of delirium burden in mechanically ventilated patients, beginning in the ICU and continuing throughout hospitalization, on functional neurologic outcomes up to 2.5 years following critical illness. METHODS: Prospective cohort study of enrolling 178 consecutive mechanically ventilated adult medical and surgical ICU patients between October 2013 and May 2016. Altogether, patients were assessed daily for delirium 2941days using the Confusion Assessment Method for the ICU (CAM-ICU). Hospitalization delirium burden (DB) was quantified as number of hospital days with delirium divided by total days at risk. Survival status up to 2.5 years and neurologic outcomes using the Glasgow Outcome Scale were recorded at discharge 3, 6, and 12 months post-discharge. RESULTS: Of 178 patients, 19 (10.7%) were excluded from outcome analyses due to persistent coma. Among the remaining 159, 123 (77.4%) experienced delirium. DB was independently associated with >4-fold increased mortality at 2.5 years following ICU admission (adjusted hazard ratio [aHR], 4.77; 95% CI, 2.10-10.83; P < .001), and worse neurologic outcome at discharge (adjusted odds ratio [aOR], 0.02; 0.01-0.09; P < .001), 3 (aOR, 0.11; 0.04-0.31; P < .001), 6 (aOR, 0.10; 0.04-0.29; P < .001), and 12 months (aOR, 0.19; 0.07-0.52; P = .001). DB in the ICU alone was not associated with mortality (HR, 1.79; 0.93-3.44; P = .082) and predicted neurologic outcome less strongly than entire hospital stay DB. Similarly, the number of delirium days in the ICU and for whole hospitalization were not associated with mortality (HR, 1.00; 0.93-1.08; P = .917 and HR, 0.98; 0.94-1.03, P = .535) nor with neurological outcomes, except for the association between ICU delirium days and neurological outcome at discharge (OR, 0.90; 0.81-0.99, P = .038). CONCLUSIONS: Delirium burden throughout hospitalization independently predicts long term neurologic outcomes and death up to 2.5 years after critical illness, and is more predictive than delirium burden in the ICU alone and number of delirium days.


Subject(s)
Delirium/mortality , Delirium/physiopathology , Intensive Care Units , Aged , Analgesics/therapeutic use , Coma/mortality , Coma/physiopathology , Critical Illness/mortality , Female , Follow-Up Studies , Humans , Hypnotics and Sedatives/therapeutic use , Length of Stay , Male , Middle Aged , Nervous System Diseases/etiology , Prevalence , Prospective Studies , Respiration, Artificial
14.
J Clin Neurophysiol ; 38(5): 366-375, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34155185

ABSTRACT

PURPOSE: Triphasic waves arising in patients with toxic metabolic encephalopathy (TME) are often considered different from generalized periodic discharges (GPDs) in patients with generalized nonconvulsive status epilepticus (GNCSE). The primary objective of this study was to investigate whether a common mechanism can explain key aspects of both triphasic waves in TME and GPDs in GNCSE. METHOD: A neural mass model was used for the simulation of EEG patterns in patients with acute hepatic encephalopathy, a common etiology of TME. Increased neuronal excitability and impaired synaptic transmission because of elevated ammonia levels in acute hepatic encephalopathy patients were used to explain how triphasic waves and GNCSE arise. The effect of gamma-aminobutyric acid-ergic drugs on epileptiform activity, simulated with a prolonged duration of the inhibitory postsynaptic potential, was also studied. RESULTS: The simulations show that a model that includes increased neuronal excitability and impaired synaptic transmission can account for both the emergence of GPDs and GNCSE and their suppression by gamma-aminobutyric acid-ergic drugs. CONCLUSIONS: The results of this study add to evidence from other studies calling into question the dichotomy between triphasic waves in TME and GPDs in GNCSE and support the hypothesis that all GPDs, including those arising in TME patients, occur via a common mechanism.


Subject(s)
Brain Diseases , Status Epilepticus , Electroencephalography , Humans
15.
Clin Neurophysiol ; 132(1): 1-12, 2021 01.
Article in English | MEDLINE | ID: mdl-33248430

ABSTRACT

OBJECTIVE: Brain Age Index (BAI), calculated from sleep electroencephalography (EEG), has been proposed as a biomarker of brain health. This study quantifies night-to-night variability of BAI and establishes probability thresholds for inferring underlying brain pathology based on a patient's BAI. METHODS: 86 patients with multiple nights of consecutive EEG recordings were selected from Epilepsy Monitoring Unit patients whose EEGs reported as within normal limits. While EEGs with epileptiform activity were excluded, the majority of patients included in the study had a diagnosis of chronic epilepsy. BAI was calculated for each 12-hour segment of patient data using a previously established algorithm, and the night-to-night variability in BAI was measured. RESULTS: The within-patient night-to-night standard deviation in BAI was 7.5 years. Estimates of BAI derived by averaging over 2, 3, and 4 nights had standard deviations of 4.7, 3.7, and 3.0 years, respectively. CONCLUSIONS: Averaging BAI over n nights reduces night-to-night variability of BAI by a factor of n, rendering BAI a more suitable biomarker of brain health at the individual level. A brain age risk lookup table of results provides thresholds above which a patient has a high probability of excess BAI. SIGNIFICANCE: With increasing ease of EEG acquisition, including wearable technology, BAI has the potential to track brain health and detect deviations from normal physiologic function. The measure of night-to-night variability and how this is reduced by averaging across multiple nights provides a basis for using BAI in patients' homes to identify patients who should undergo further investigation or monitoring.


Subject(s)
Age Factors , Algorithms , Brain/physiology , Electroencephalography , Sleep/physiology , Adult , Aging/physiology , Brain Diseases/diagnosis , Chronic Disease , Epilepsy/diagnosis , Female , Humans , Male , Middle Aged , Signal-To-Noise Ratio , Sleep Stages/physiology , Time Factors , Wakefulness/physiology
16.
JAMA Netw Open ; 3(9): e2017357, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32986106

ABSTRACT

Importance: Dementia is an increasing cause of disability and loss of independence in the elderly population yet remains largely underdiagnosed. A biomarker for dementia that can identify individuals with or at risk for developing dementia may help close this diagnostic gap. Objective: To investigate the association between a sleep electroencephalography-based brain age index (BAI), the difference between chronological age and brain age estimated using the sleep electroencephalogram, and dementia. Design, Setting, and Participants: In this retrospective cross-sectional study of 9834 polysomnograms, BAI was computed among individuals with previously determined dementia, mild cognitive impairment (MCI), or cognitive symptoms but no diagnosis of MCI or dementia, and among healthy individuals without dementia from August 22, 2008, to June 4, 2018. Data were analyzed from November 15, 2018, to June 24, 2020. Exposure: Dementia, MCI, and dementia-related symptoms, such as cognitive change and memory impairment. Main Outcomes and Measures: The outcome measures were the trend in BAI when moving from groups ranging from healthy, to symptomatic, to MCI, to dementia and pairwise comparisons of BAI among these groups. Findings: A total of 5144 sleep studies were included in BAI examinations. Patients in these studies had a median (interquartile range) age of 54 (43-65) years, and 3026 (59%) were men. The patients included 88 with dementia, 44 with MCI, 1075 who were symptomatic, and 2336 without dementia. There was a monotonic increase in mean (SE) BAI from the nondementia group to the dementia group (nondementia: 0.20 [0.42]; symptomatic: 0.58 [0.41]; MCI: 1.65 [1.20]; dementia: 4.18 [1.02]; P < .001). Conclusions and Relevance: These findings suggest that a sleep-state electroencephalography-based BAI shows promise as a biomarker associated with progressive brain processes that ultimately result in dementia.


Subject(s)
Aging/physiology , Brain/physiopathology , Cognitive Dysfunction/physiopathology , Dementia/physiopathology , Electroencephalography , Sleep/physiology , Adult , Aged , Aged, 80 and over , Brain/physiology , Case-Control Studies , Cognitive Aging/physiology , Cross-Sectional Studies , Female , Humans , Male , Mental Status and Dementia Tests , Middle Aged , Polysomnography , Retrospective Studies
17.
Eng. sanit. ambient ; 25(4): 583-596, jul.-ago. 2020. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1133804

ABSTRACT

RESUMO O objetivo deste estudo foi investigar as águas superficiais e os níveis foliares dos elementos-traço (Cu, Zn, Cd e Pb) da Avicennia schaueriana na área de proteção ambiental (APA) Tinharé-Boipeba, litoral sul da Bahia, com ênfase na relação entre a qualidade ambiental e o gerenciamento costeiro. Mensuraram-se in situ variáveis físico-químicas nas águas superficiais, e tomaram-se alíquotas para análises microbiológicas. Também foram coletadas folhas de árvores de mangue em nove estações amostrais. Realizou-se a leitura dos elementos-traço por espectrometria de absorção atômica com chama (F-AAS). As análises físico-químicas e microbiológicas das águas superficiais, ainda que preliminares, indicaram perda de qualidade e desafios ao saneamento, os quais merecem a atenção de autoridades sanitárias ou de saúde pública e consulta à comunidade para elaboração de soluções técnicas compatíveis com os usos da natureza e modos de vida tradicionais na APA. Os níveis foliares dos metais foram normais e não tóxicos, sendo menores do que em áreas costeiras impactadas. Os bosques de mangue encontram-se em bom estado de conservação e servem de área de referência, recomendando-se o monitoramento dos elementos-traço nas folhas ou sedimentos de mangue e qualidade da água. Esta pesquisa tem relevância à conservação dos manguezais, aos usos culturais da natureza e ao gerenciamento costeiro.


ABSTRACT The objective of this study was to investigate the surface waters and leaf levels of trace elements (Cu, Zn, Cd, and Pb) of the Avicennia schaueriana in the Tinharé-Boipeba Environmental Protection Area (APA), South Coast of Bahia, with emphasis to the relationship between environmental quality and coastal management. Physical-chemical variables were measured in situ in surface waters and aliquots were taken for microbiological analysis. Also, leaves of mangrove trees were collected at nine sampling stations. The trace element reading was performed by F-AAS. Physical-chemical and microbiological analyzes of surface water, although preliminary, indicated that there is a loss of quality and challenges to sanitation, which deserve the attention of sanitary authorities, and of public health, and consultation with the community to elaborate technical solutions compatible with the uses of nature and traditional lifestyles in APA. Leaf metal levels were normal and nontoxic, being lower than in impacted coastal areas. Mangrove forests are in good state of conservation and serve as a reference area, recommending the monitoring of trace elements in mangrove leaves or sediments and water quality. This research has relevance to the conservation of mangroves, cultural uses of nature and coastal management.

18.
Neurobiol Aging ; 88: 150-155, 2020 04.
Article in English | MEDLINE | ID: mdl-31932049

ABSTRACT

The brain age index (BAI) measures the difference between an individual's apparent "brain age" (BA; estimated by comparing EEG features during sleep from an individual with age norms), and their chronological age (CA); that is BAI = BA-CA. Here, we evaluate whether BAI predicts life expectancy. Brain age was quantified using a previously published machine learning algorithm for a cohort of participants ≥40 years old who underwent an overnight sleep electroencephalogram (EEG) as part of the Sleep Heart Health Study (n = 4877). Excess brain age (BAI >0) was associated with reduced life expectancy (adjusted hazard ratio: 1.12, [1.03, 1.21], p = 0.002). Life expectancy decreased by -0.81 [-1.44, -0.24] years per standard-deviation increase in BAI. Our findings show that BAI, a sleep EEG-based biomarker of the deviation of sleep microstructure from patterns normal for age, is an independent predictor of life expectancy.


Subject(s)
Aging , Brain/physiology , Electroencephalography , Life Expectancy , Sleep/physiology , Biomarkers , Predictive Value of Tests
19.
Epilepsia ; 60(12): 2508-2518, 2019 12.
Article in English | MEDLINE | ID: mdl-31745988

ABSTRACT

OBJECTIVE: We evaluated the impact of monitoring indication, early electroencephalography (EEG), and clinical features on seizure risk in all neonates undergoing continuous EEG (cEEG) monitoring following a standardized monitoring protocol. METHODS: All cEEGs from unique neonates 34-48 weeks postmenstrual age monitored from 1/2011-10/2017 (n = 291) were included. We evaluated the impact of cEEG monitoring indication (acute neonatal encephalopathy [ANE], suspicious clinical events [SCEs], or other high-risk conditions [OHRs]), age, medication status, and early EEG abnormalities (including the presence of epileptiform discharges and abnormal background continuity, amplitude, asymmetry, asynchrony, excessive sharp transients, and burst suppression) on time to first seizure and overall seizure risk using Kaplan-Meier survival curves and multivariable Cox proportional hazards models. RESULTS: Seizures occurred in 28% of high-risk neonates. Discontinuation of monitoring after 24 hours of seizure-freedom would have missed 8.5% of neonates with seizures. Overall seizure risk was lower in neonates monitored for ANE compared to OHR (P = .004) and trended lower compared to SCE (P = .097). The time course of seizure presentation varied by group, where the probability of future seizure was less than 1% after 17 hours of seizure-free monitoring in the SCE group, but required 42 hours in the OHR group, and 73 hours in the ANE group. The presence of early epileptiform discharges increased seizure risk in each group (ANE: adjusted hazard ratio [aHR] 4.32, 95% confidence interval [CI] 1.23-15.13, P = .022; SCE: aHR 10.95, 95% CI 4.77-25.14, P < 1e-07; OHR: aHR 56.90, 95% CI 10.32-313.72, P < 1e-05). SIGNIFICANCE: Neonates who undergo cEEG are at high risk for seizures, and risk varies by monitoring indication and early EEG findings. Seizures are captured in nearly all neonates undergoing monitoring for SCE within 24 hours of cEEG monitoring. Neonates monitored for OHR and ANE can present with delayed seizures and require longer durations of monitoring. Early epileptiform discharges are the best early EEG feature to predict seizure risk.


Subject(s)
Electroencephalography/trends , Seizures/diagnosis , Seizures/physiopathology , Electroencephalography/methods , Female , Humans , Infant, Newborn , Male , Predictive Value of Tests , Risk Factors
20.
J Comput Neurosci ; 47(2-3): 109-124, 2019 12.
Article in English | MEDLINE | ID: mdl-31506807

ABSTRACT

Acute hepatic encephalopathy (AHE) due to acute liver failure is a common form of delirium, a state of confusion, impaired attention, and decreased arousal. The electroencephalogram (EEG) in AHE often exhibits a striking abnormal pattern of brain activity, which epileptiform discharges repeat in a regular repeating pattern. This pattern is known as generalized periodic discharges, or triphasic-waves (TPWs). While much is known about the neurophysiological mechanisms underlying AHE, how these mechanisms relate to TPWs is poorly understood. In order to develop hypotheses how TPWs arise, our work builds a computational model of AHE (AHE-CM), based on three modifications of the well-studied Liley model which emulate mechanisms believed central to brain dysfunction in AHE: increased neuronal excitability, impaired synaptic transmission, and enhanced postsynaptic inhibition. To relate our AHE-CM to clinical EEG data from patients with AHE, we design a model parameter optimization method based on particle filtering (PF-POM). Based on results from 7 AHE patients, we find that the proposed AHE-CM not only performs well in reproducing important aspects of the EEG, namely the periodicity of triphasic waves (TPWs), but is also helpful in suggesting mechanisms underlying variation in EEG patterns seen in AHE. In particular, our model helps explain what conditions lead to increased frequency of TPWs. In this way, our model represents a starting point for exploring the underlying mechanisms of brain dynamics in delirium by relating microscopic mechanisms to EEG patterns.


Subject(s)
Brain/physiopathology , Computer Simulation , Hepatic Encephalopathy/physiopathology , Models, Neurological , Electroencephalography , Humans
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