Treatment effects of N-acetyl cysteine on resting-state functional MRI and cognitive performance in patients with chronic mild traumatic brain injury: a longitudinal study.

Mild traumatic brain injury (mTBI) is a significant public health concern, specially characterized by a complex pattern of abnormal neural activity and functional connectivity. It is often associated with a broad spectrum of short-term and long-term cognitive and behavioral symptoms including memory dysfunction, headache, and balance difficulties. Furthermore, there is evidence that oxidative stress significantly contributes to these symptoms and neurophysiological changes. The purpose of this study was to assess the effect of N-acetylcysteine (NAC) on brain function and chronic symptoms in mTBI patients. Fifty patients diagnosed with chronic mTBI participated in this study. They were categorized into two groups including controls (CN, n = 25), and patients receiving treatment with N-acetyl cysteine (NAC, n = 25). NAC group received 50 mg/kg intravenous (IV) medication once a day per week. In the rest of the week, they took one 500 mg NAC tablet twice per day. Each patient underwent rs-fMRI scanning at two timepoints including the baseline and 3 months later at follow-up, while the NAC group received a combination of oral and IV NAC over that time. Three rs-fMRI metrics were measured including fractional amplitude of low frequency fluctuations (fALFF), degree centrality (DC), and functional connectivity strength (FCS). Neuropsychological tests were also assessed at the same day of scanning for each patient. The alteration of rs-fMRI metrics and cognitive scores were measured over 3 months treatment with NAC. Then, the correlation analysis was executed to estimate the association of rs-fMRI measurements and cognitive performance over 3 months (p < 0.05). Two significant group-by-time effects demonstrated the changes of rs-fMRI metrics particularly in the regions located in the default mode network (DMN), sensorimotor network, and emotional circuits that were significantly correlated with cognitive function recovery over 3 months treatment with NAC (p < 0.05). NAC appears to modulate neural activity and functional connectivity in specific brain networks, and these changes could account for clinical improvement. This study confirmed the short-term therapeutic efficacy of NAC in chronic mTBI patients that may contribute to understanding of neurophysiological effects of NAC in mTBI. These findings encourage further research on long-term neurobehavioral assessment of NAC assisting development of therapeutic plans in mTBI.

Machine learning-based classification of chronic traumatic brain injury using hybrid diffusion imaging.

Background and purpose: Traumatic brain injury (TBI) can cause progressive neuropathology that leads to chronic impairments, creating a need for biomarkers to detect and monitor this condition to improve outcomes. This study aimed to analyze the ability of data-driven analysis of diffusion tensor imaging (DTI) and neurite orientation dispersion imaging (NODDI) to develop biomarkers to infer symptom severity and determine whether they outperform conventional T1-weighted imaging. Materials and methods: A machine learning-based model was developed using a dataset of hybrid diffusion imaging of patients with chronic traumatic brain injury. We first extracted the useful features from the hybrid diffusion imaging (HYDI) data and then used supervised learning algorithms to classify the outcome of TBI. We developed three models based on DTI, NODDI, and T1-weighted imaging, and we compared the accuracy results across different models. Results: Compared with the conventional T1-weighted imaging-based classification with an accuracy of 51.7-56.8%, our machine learning-based models achieved significantly better results with DTI-based models at 58.7-73.0% accuracy and NODDI with an accuracy of 64.0-72.3%. Conclusion: The machine learning-based feature selection and classification algorithm based on hybrid diffusion features significantly outperform conventional T1-weighted imaging. The results suggest that advanced algorithms can be developed for inferring symptoms of chronic brain injury using feature selection and diffusion-weighted imaging.

Neuropsychological Comparison of Guilt and Grief: A Review of Guilt Aspects in Prolonged Grief Disorder.

Taking an integrative approach toward developmental psychology and neurophysiology, this review selects findings from the psychological and medical literature on guilt and bereavement that are relevant to considering whether and how guilt contributes to the development of prolonged grief disorder (PGD) in bereaved persons. Mention of guilt is ubiquitous in literature on general grief and PGD, including 54 articles related to the neuropsychological development and manifestations of guilt and grief, as well as their neuroimaging correlates, that met scoping review criteria. However, mechanisms connecting guilt to development of PGD are scarce. Aspects of guilt are conceptually connected to many PGD criteria, opening avenues to explore treatment of PGD by targeting guilt. Positive and prosocial aspects of guilt are especially neglected in the treatment of psychiatric disorders, and consideration of these aspects may improve interventions for PGD such as complicated grief treatment.

Deep learning-based multimodality classification of chronic mild traumatic brain injury using resting-state functional MRI and PET imaging.

Mild traumatic brain injury (mTBI) is a public health concern. The present study aimed to develop an automatic classifier to distinguish between patients with chronic mTBI (n = 83) and healthy controls (HCs) (n = 40). Resting-state functional MRI (rs-fMRI) and positron emission tomography (PET) imaging were acquired from the subjects. We proposed a novel deep-learning-based framework, including an autoencoder (AE), to extract high-level latent and rectified linear unit (ReLU) and sigmoid activation functions. Single and multimodality algorithms integrating multiple rs-fMRI metrics and PET data were developed. We hypothesized that combining different imaging modalities provides complementary information and improves classification performance. Additionally, a novel data interpretation approach was utilized to identify top-performing features learned by the AEs. Our method delivered a classification accuracy within the range of 79-91.67% for single neuroimaging modalities. However, the performance of classification improved to 95.83%, thereby employing the multimodality model. The models have identified several brain regions located in the default mode network, sensorimotor network, visual cortex, cerebellum, and limbic system as the most discriminative features. We suggest that this approach could be extended to the objective biomarkers predicting mTBI in clinical settings.

Positron Emission Tomography-Based Assessment of Cognitive Impairment and Dementias, Critical Role of Fluorodeoxyglucose in such Settings.

Positron emission tomography (PET) has been a key component in the diagnostic armamentarium for assessing neurodegenerative diseases such as Alzheimer or Parkinson disease. PET imaging has been useful for diagnosing these disorders, identifying their pathophysiology, and following their treatment. Further, PET imaging has been extensively used for both clinical and research purposes, particularly for helping with potential therapeutic approaches for managing neurodegenerative diseases. This article will review the current literature regarding PET imaging in patients with neurodegenerative disorders. This includes an evaluation of the most commonly used tracer fluorodeoxyglucose that measures cerebral glucose metabolism, tracers that assess neurotransmitter systems, and tracers designed to reveal disease-specific pathophysiological processes. With the continuing development of an expanding variety of radiopharmaceuticals, PET imaging will likely play a prominent role in future research and clinical applications for neurodegenerative diseases.

Cerebral Blood Flow and Brain Functional Connectivity Changes in Older Adults Participating in a Mindfulness-Based Stress Reduction Program.

There is a growing interest in the potential beneficial effects of mindfulness meditation training in protecting against age-related physical, emotional, and cognitive decline. The current prospective, single-center, single-arm study investigated if functional magnetic resonance imaging-based changes in cerebral blood flow and brain functional connectivity could be observed in 11 elderly adults (mean age 79) after participation in a Mindfulness-Based Stress Reduction (MBSR) program. The results showed significantly (p < 0.05) altered cerebral blood flow and functional connectivity in the cingulate gyrus, limbic structures, and subregions of the temporal and frontal lobes, similar to findings of other meditation-related studies in younger populations. Furthermore, these changes were also associated with significant improvements in depression symptoms. This study suggests that the MBSR program can potentially modify cerebral blood flow and connectivity in this population.

An updated classification of meditation methods using principles of taxonomy and systematics.

This paper revisits the proposal for the classification of meditation methods which we introduced in our initial 2013 publication, "Toward a Universal Taxonomy and Definition of Meditation". At that time, we advanced the thesis that meditation methods could be effectively segregated into three orthogonal categories by integrating the taxonomic principle of functional essentialism and the paradigm of Affect and Cognition; and we presented relevant research findings which supported that assertion. This iteration expands upon those theoretical and methodological elements by articulating a more comprehensive Three Tier Classification System which accounts for the full range of meditation methods; and demonstrates how recent neuroscience research continues to validate and support our thesis. This paper also introduces a novel criterion-based protocol for formulating classification systems of meditation methods, and demonstrates how this model can be used to compare and evaluate various other taxonomy proposals that have been published over the past 15 years.

Identification of chronic mild traumatic brain injury using resting state functional MRI and machine learning techniques.

Mild traumatic brain injury (mTBI) is a major public health concern that can result in a broad spectrum of short-term and long-term symptoms. Recently, machine learning (ML) algorithms have been used in neuroscience research for diagnostics and prognostic assessment of brain disorders. The present study aimed to develop an automatic classifier to distinguish patients suffering from chronic mTBI from healthy controls (HCs) utilizing multilevel metrics of resting-state functional magnetic resonance imaging (rs-fMRI). Sixty mTBI patients and forty HCs were enrolled and allocated to training and testing datasets with a ratio of 80:20. Several rs-fMRI metrics including fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), degree centrality (DC), voxel-mirrored homotopic connectivity (VMHC), functional connectivity strength (FCS), and seed-based FC were generated from two main analytical categories: local measures and network measures. Statistical two-sample t-test was employed comparing between mTBI and HCs groups. Then, for each rs-fMRI metric the features were selected extracting the mean values from the clusters showing significant differences. Finally, the support vector machine (SVM) models based on separate and multilevel metrics were built and the performance of the classifiers were assessed using five-fold cross-validation and via the area under the receiver operating characteristic curve (AUC). Feature importance was estimated using Shapley additive explanation (SHAP) values. Among local measures, the range of AUC was 86.67-100% and the optimal SVM model was obtained based on combined multilevel rs-fMRI metrics and DC as a separate model with AUC of 100%. Among network measures, the range of AUC was 80.42-93.33% and the optimal SVM model was obtained based on the combined multilevel seed-based FC metrics. The SHAP analysis revealed the DC value in the left postcentral and seed-based FC value between the motor ventral network and right superior temporal as the most important local and network features with the greatest contribution to the classification models. Our findings demonstrated that different rs-fMRI metrics can provide complementary information for classifying patients suffering from chronic mTBI. Moreover, we showed that ML approach is a promising tool for detecting patients with mTBI and might serve as potential imaging biomarker to identify patients at individual level. Clinical trial registration: [clinicaltrials.gov], identifier [NCT03241732].

Alterations in Functional Connectivity Measured by Functional Magnetic Resonance Imaging and the Relationship With Heart Rate Variability in Subjects After Performing Orgasmic Meditation: An Exploratory Study.

Background: We measured changes in resting brain functional connectivity, with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), associated with a creative meditation practice that is augmented by clitoral stimulation and is designed to not only achieve a spiritual experience but to help individuals manage their most intimate personal relationships. Briefly, the meditative state is attained by both the male and female participants while the male stimulates the woman's clitoris. The goal of this practice, called orgasmic meditation (OM), according to the practitioners is not sexual, but to use the focus on clitoral stimulation to facilitate a meditative state of connectedness and calm alertness between the two participants. Methods: fMRI was acquired on 20 pairs of subjects shortly following one of two states that were randomized in their order - during the OM practice or during a neutral condition. The practice is performed while the female is lying down on pillows with the clitoris exposed. During the practice, the male performs digital stimulation of the clitoris for 15 min. Resting BOLD image acquisition was performed at completion of the practice to assess changes in functional connectivity associated with the performance of the practice. Results: The results demonstrated significant changes (p < 0.05) in functional connectivity associated with the OM compared to the neutral condition. For the entire group there was altered connectivity following the OM practice involving the left superior temporal lobe, the frontal lobe, anterior cingulate, and insula. In female subjects, there was altered connectivity involving the cerebellum, thalamus, inferior frontal lobe posterior parietal lobe, angular gyrus, amygdala and middle temporal gyrus, and prefrontal cortex. In males, functional connectivity changes involved the supramarginal gyrus, cerebellum, and orbitofrontal gyrus, cerebellum, parahippocampus, inferior temporal gyrus, and anterior cingulate. Conclusion: Overall, these findings suggest a complex pattern of functional connectivity changes occurring in both members of the couple pair that result from this unique meditation practice. The changes represent a hybrid of functional connectivity findings with some similarities to meditation based practices and some with sexual stimulation and orgasm. This study has broader implications for understanding the dynamic relationship between sexuality and spirituality.

N-acetyl cysteine administration affects cerebral blood flow as measured by arterial spin labeling MRI in patients with multiple sclerosis.

BACKGROUND: The purpose of this study was to explore if administration of N-acetyl-cysteine (NAC) in patients with multiple sclerosis (MS) resulted in altered cerebral blood flow (CBF) based on Arterial Spin Labeling (ASL) magnetic resonance imaging (MRI). METHODS: Twenty-three patients with mild to moderate MS, (17 relapsing remitting and 6 primary progressive) were randomized to either NAC plus standard of care (N = 11), or standard of care only (N = 12). The experimental group received NAC intravenously (50 mg/kg) once per week and orally (500mg 2x/day) the other six days. Patients in both groups were evaluated initially and after 2 months (of receiving the NAC or waitlist control) with ASL MRI to measure CBF. Clinical symptom questionnaires were also completed at both time points. RESULTS: The CBF data showed significant differences in several brain regions including the pons, midbrain, left temporal and frontal lobe, left thalamus, right middle frontal lobe and right temporal/hippocampus (p < 0.001) in the MS group after treatment with NAC, when compared to the control group. Self-reported scores related to cognition and attention were also significantly improved in the NAC group as compared to the control group. CONCLUSIONS: The results of this study suggest that NAC administration alters resting CBF in MS patients, and this is associated with qualitative improvements in cognition and attention. Given these findings, large scale efficacy studies will be of value to determine the potential clinical impact of NAC over the course of illness in patients with MS, as well as the most effective dosages and differential effects across subpopulations.

Hybrid diffusion imaging reveals altered white matter tract integrity and associations with symptoms and cognitive dysfunction in chronic traumatic brain injury.

The detection and association of in vivo biomarkers in white matter (WM) pathology after acute and chronic mild traumatic brain injury (mTBI) are needed to improve care and develop therapies. In this study, we used the diffusion MRI method of hybrid diffusion imaging (HYDI)to detect white matter alterations in patients with chronic TBI (cTBI). 40 patients with cTBI presenting symptoms at least three months post injury, and 17 healthy controls underwent magnetic resonance HYDI. cTBI patients were assessed with a battery of neuropsychological tests. A voxel-wise statistical analysis within the white matter skeleton was performed to study between group differences in the diffusion models. In addition, a partial correlation analysis controlling for age, sex, and time after injury was performed within the cTBI cohort, to test for associations between diffusion metrics and clinical outcomes. The advanced diffusion modeling technique of neurite orientation dispersion and density imaging (NODDI) showed large clusters of between-group differences resulting in lower values in the cTBI across the brain, where the single compartment diffusion tensor model failed to show any significant results. However, the diffusion tensor model appeared to be just as sensitive in detecting self-reported symptoms in the cTBI population using a within-group correlation. To the best of our knowledge this study provides the first application of HYDI in evaluation of cTBI using combined DTI and NODDI, significantly enhancing our understanding of the effects of concussion on white matter microstructure and emphasizing the utility of full characterization of complex diffusion to diagnose, monitor, and treat brain injury.

Alterations in cerebral glucose metabolism as measured by 18F-fluorodeoxyglucose-PET in patients with persistent postconcussion syndrome.

BACKGROUND: Many patients who have traumatic brain injury experience a wide range of psychiatric and neurological symptoms (including impairment in functional status, cognition, and mood), and if persistent are referred to as persistent postconcussion syndrome (PCS). To our knowledge, this is the first study to broadly evaluate metabolic dysregulation in a heterogenous patient population meeting the criteria for PCS. METHODS: A total of 64 PCS patients and 37 healthy controls underwent 18F-fluorodeoxyglucose-PET (18F-FDG-PET) scanning, and 70 brain structures (including left and right structures where appropriate) were analyzed in each subject. RESULTS: Compared to the brains of healthy controls, those of PCS patients demonstrated 15 hypermetabolic and 23 hypometabolic regions. Metabolic changes in the brains of PCS patients were subsequently correlated with various indices of symptom severity, mood, and physical/cognitive function. Among PCS patients, increased metabolism in the right cingulate gyrus correlated with the severity of postconcussion symptoms. Conversely, increased metabolism in the left temporal lobe was associated with both improved mood and measures of adaptability/rehabilitation. Furthermore, increased metabolism in the bilateral orbitofrontal regions correlated with improved working memory. CONCLUSIONS: Overall, these findings suggest a complex pattern of cerebral metabolism in PCS patients, with a mixture of hypometabolic and hypermetabolic regions that correlate with various symptoms, highlighting both potential pathological and compensatory mechanisms in PCS. The findings also suggest that FDG PET is useful for providing neurophysiological information in the evaluation of patients with PCS and may help guide future targeted therapies.

Spiritual Fitness: A New Dimension in Alzheimer's Disease Prevention.

BACKGROUND: Religious and spiritual interventions may have an effect on Alzheimer's disease prevention. Kirtan Kriya meditation has been shown to mitigate the deleterious effects of chronic stress on cognition, reverse memory loss, and create psychological and spiritual wellbeing, which may reduce multiple drivers of Alzheimer's disease risk. OBJECTIVE: To detail a new concept in medicine called Spiritual Fitness, a merging of stress reduction, basic wellbeing, and psycho/spiritual wellbeing to prevent Alzheimer's disease. METHODS: The literature on the topics mentioned above is described, including an in-depth discussion on why and how each are critical to advancing the future of Alzheimer's disease prevention. The many negative effects of chronic stress, and the benefits of Kirtan Kriya, are reviewed. The four pillars of basic wellbeing, six practical aspects of psychological wellbeing, and the four new non-sectarian features of spiritual fitness are then disclosed. Moreover, instructions on practicing Kirtan Kriya are offered in the Supplementary Material. CONCLUSION: Religious and spiritual practices, including Kirtan Kriya, are crucial components in the development of enhanced cognition and well-being, which may help prevent and, in some cases, reverse cognitive decline. The key point of this review is that making a commitment to live a brain longevity lifestyle including spiritual fitness is a critically important way for aging Alzheimer's disease free. We hope that this article will inspire scientists, clinicians, and patients to embrace this new concept of spiritual fitness and make it a part of every multidomain program for the prevention of cognitive disability.

Resting-State Functional MRI Metrics in Patients With Chronic Mild Traumatic Brain Injury and Their Association With Clinical Cognitive Performance.

Mild traumatic brain injury (mTBI) accounts for more than 80% of people experiencing brain injuries. Symptoms of mTBI include short-term and long-term adverse clinical outcomes. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) was conducted to measure voxel-based indices including fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) in patients suffering from chronic mTBI; 64 patients with chronic mTBI at least 3 months post injury and 40 healthy controls underwent rs-fMRI scanning. Partial correlation analysis controlling for age and gender was performed within mTBI cohort to explore the association between rs-fMRI metrics and neuropsychological scores. Compared with controls, chronic mTBI patients showed increased fALFF in the left middle occipital cortex (MOC), right middle temporal cortex (MTC), and right angular gyrus (AG), and increased ReHo in the left MOC and left posterior cingulate cortex (PCC). Enhanced FC was observed from left MOC to right precuneus; from right MTC to right superior temporal cortex (STC), right supramarginal, and left inferior parietal cortex (IPC); and from the seed located at right AG to left precuneus, left superior medial frontal cortex (SMFC), left MTC, left superior temporal cortex (STC), and left MOC. Furthermore, the correlation analysis revealed a significant correlation between neuropsychological scores and fALFF, ReHo, and seed-based FC measured from the regions with significant group differences. Our results demonstrated that alterations of low-frequency oscillations in chronic mTBI could be representative of disruption in emotional circuits, cognitive performance, and recovery in this cohort.

Applications of Hybrid PET/Magnetic Resonance Imaging in Central Nervous System Disorders.

PET with 18F-fluorodeoxyglucose (FDG) is used to assess a wide array of inflammatory and neoplastic disorders. FDG-PET has shown particular utility in the evaluation of disorders of the central nervous system (CNS). Although fused PET/computed tomography (CT) is frequently used across the globe for these diseases, recent evidence has pointed to PET/magnetic resonance (MR) imaging as a more sensitive and specific molecular imaging modality. This article reviews the literature regarding the advantages of PET/MR imaging compared with PET/CT imaging, especially in CNS disease. It also introduces a new concept for PET-based evaluation of patients with neurodegenerative disorders: global disease assessment.

Differences in brain activity patterns during creative idea generation between eminent and non-eminent thinkers.

An influential model of the neural mechanisms of creative thought suggests that creativity is manifested in the joint contributions of the Default Mode Network (DMN; a set of regions in the medial PFC, lateral and medial parietal cortex, and the medial temporal lobes) and the executive networks within the dorsolateral PFC. Several empirical reports have offered support for this model by showing that complex interactions between these brain systems account for individual differences in creative performance. The present study examined whether the engagement of these regions in idea generation is modulated by one's eminence in a creativity-related field. Twenty (n â€‹= â€‹20) healthy eminent creators from diverse fields of expertise and a 'smart' comparison group of sixteen (n â€‹= â€‹16) age- and education-matched non-eminent thinkers were administered a creative generation task (an adaptation of the Alternative Uses Task) and a control perceptual task, while undergoing functional magnetic resonance imaging (fMRI). The participants' verbal responses were recorded through a noise-canceling microphone and were later coded for fluency and accuracy. Behavioral and fMRI analyses revealed commonalities between groups, but also distinct patterns of activation in default mode and executive brain regions between the eminent and the non-eminent participants during creative thinking. We interpret these findings in the context of the well-documented contributions of these regions in the generation of creative ideas as modulated, in this study, by participants' creative eminence.

Differences in brain morphometry associated with creative performance in high- and average-creative achievers.

Nearly everyone has the ability for creative thought. Yet, certain individuals create works that propel their fields, challenge paradigms, and advance the world. What are the neurobiological factors that might underlie such prominent creative achievement? In this study, we focus on morphometric differences in brain structure between high creative achievers from diverse fields of expertise and a 'smart' comparison group of age-, intelligence-, and education-matched average creative achievers. Participants underwent a high-resolution structural brain imaging scan and completed a series of intelligence, creative thinking, personality, and creative achievement measures. We examined whether high and average creative achievers could be distinguished based on the relationship between morphometric brain measures (cortical area and thickness) and behavioral measures. Although participants' performance on the behavioral measures did not differ between the two groups aside from creative achievement, the relationship between posterior parietal cortex morphometry and creativity, intelligence, and personality measures depended on group membership. These results suggest that extraordinary creativity may be associated with measurable structural brain differences, especially within parietal cortex.

N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study.

Background: Multiple Sclerosis (MS) is an autoimmune disease marked by progressive neurocognitive injury. Treatment options affording neuroprotective effects remain largely experimental. The purpose of this proof of concept study was to explore the effects of N-acetyl-cysteine (NAC) on cerebral glucose metabolism (CMRGlu) and symptoms in patients with multiple sclerosis (MS). Methods: Twenty-four patients with MS were randomized to either NAC plus standard of care, or standard of care only (waitlist control). The experimental group received NAC intravenously once per week and orally the other 6 days. Patients in both groups were evaluated at baseline and after 2 months (of receiving the NAC or waitlist control period) with an integrated Position Emission Tomography (PET)/ Magnetic Resonance Imaging (MRI) scanner, using 18F Fluorodeoxyglucose (FDG) to measure cerebral glucose metabolism. Following imaging evaluation at 2 months, subjects initially attributed to the standard of care arm were eligible for treatment with NAC. Clinical and symptom questionnaires were also completed initially and after 2 months. Results: The FDG PET data showed significantly increased cerebral glucose metabolism in several brain regions including the caudate, inferior frontal gyrus, lateral temporal gyrus, and middle temporal gyrus (p < 0.05) in the MS group treated with NAC, as compared to the control group. Self-reported scores related to cognition and attention were also significantly improved in the NAC group as compared to the control group. Conclusions: The results of this study suggest that NAC positively affects cerebral glucose metabolism in MS patients, which is associated with qualitative, patient reported improvements in cognition and attention. Larger scale studies may help to determine the clinical impact of NAC on measures of functioning over the course of illness, as well as the most effective dosage and dosage regimen.

Association of ß-Amyloid Burden With Sleep Dysfunction and Cognitive Impairment in Elderly Individuals With Cognitive Disorders.

Importance: Evidence shows that sleep dysfunction and ß-amyloid (Aß) deposition work synergistically to impair brain function in individuals with normal cognition, increasing the risk of developing dementia later in life. However, whether Aß continues to play an integral role in sleep dysfunction after the onset of cognitive decline in individuals with dementia is unclear. Objective: To determine whether Aß deposition in the brain is associated with subjective measures of sleep quality and cognition in elderly individuals with cognitive disorders. Design, Setting, and Participants: A nested survey study was conducted at the Cognitive Disorders and Comprehensive Alzheimer Disease Center of Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. Participants included patients aged 65 years and older with cognitive disorders verified by neuropsychological testing. Eligible participants were identified from a referral center-based sample of patients who underwent fluorine 18-labeled florbetaben positron emission tomography imaging at Thomas Jefferson University Hospital as part of the multicenter Imaging Dementia-Evidence for Amyloid Scanning study. Data collection and analysis occurred between November 2018 and March 2019. Main Outcomes and Measures: Sleep quality was measured via responses to sleep questionnaires, Aß deposition was measured via fluorine 18-labeled florbetaben positron emission tomography, and cognition was measured via Mini-Mental State Examination (MMSE) performance. Results: Of the 67 eligible participants, 52 (77.6%) gave informed consent to participate in the study. Of the 52 enrolled participants (mean [SD] age, 76.6 [7.4] years), 27 (51.9%) were women. Daytime sleepiness was associated with Aß deposition in the brainstem (B = 0.0063; 95% CI, 0.001 to 0.012; P = .02), but not MMSE performance (B = -0.01; 95% CI, -0.39 to 0.37; P = .96). The number of nocturnal awakenings was associated with Aß deposition in the precuneus (B = 0.11; 95% CI, 0.06 to 0.17; P < .001) and poor MMSE performance (B = -2.13; 95% CI, -3.13 to -1.13; P < .001). Mediation analysis demonstrated an indirect association between Aß deposition and poor MMSE performance that relied on nocturnal awakenings as an intermediary (B = -3.99; 95% CI, -7.88 to -0.83; P = .01). Conclusions and Relevance: Nighttime sleep disruption may mediate the association between Aß and cognitive impairment, suggesting that there is an underlying sleep-dependent mechanism that links Aß burden in the brain to cognitive decline. Further elucidation of this mechanism may improve understanding of disease processes associated with Aß accumulation.