FMRI Complexity Correlates with Tau-PET and Cognitive Decline in Late-Onset and Autosomal Dominant Alzheimer's Disease.

Background: Neurofibrillary tangle pathology detected with tau-PET correlates closely with neuronal injury and cognitive symptoms in Alzheimer's disease (AD). Complexity of rs-fMRI has been demonstrated to decrease with cognitive decline in AD.

Objective: We hypothesize that the rs-fMRI complexity provides an index for tau-related neuronal injury and cognitive decline in the AD process.

Variability in objective sleep is associated with Alzheimer's pathology and cognition.

Both sleep duration and sleep efficiency have been associated with risk of Alzheimer's disease, suggesting that interventions to promote optimal sleep may be a way to reduce Alzheimer's disease risk. However, studies often focus on average sleep measures, usually from self-report questionnaires, ignoring the role of intra-individual variability in sleep across nights quantified from objective sleep measures. The current cross-sectional study sought to investigate the role of intra-individual variability in accelerometer-based objective sleep duration and sleep efficiency in relation to Alzheimer's disease pathology (-amyloid and tau) using positron emission tomography imaging and cognition (working memory, inhibitory control, verbal memory, visual memory and global cognition).

Identifying access barriers faced by rural and dispersed communities to better address their needs: implications and lessons learned for rural proofing for health in the Americas and beyond.

Introduction: Universal access to health services and universal health coverage are needed to achieve good health for all, yet rural communities face a variety of access barriers. As part of an effort to 'rural proof' health systems, it is therefore imperative to identify and act on the factors limiting access to health services by rural and indigenous communities. This article provides a comprehensive overview of the wide range of access barriers faced by rural and remote communities in two countries where barrier assessments were conducted.

Worst-Case X-ray Photon Energies in Ultrashort Pulse Laser Processing.

Ultrashort pulse laser processing can result in the secondary generation of unwanted X-rays if a critical laser irradiance of about 10 W cm is exceeded. Spectral X-ray emissions were investigated during the processing of tungsten and steel using three complementary spectrometers (based on CdTe and silicon drift detectors) simultaneously for the identification of a worst-case spectral scenario. Therefore, maximum X-ray photon energies were determined, and corresponding dose equivalent rates were calculated.

Higher baseline levels of CSF inflammation increase risk of incident mild cognitive impairment and Alzheimer's disease dementia.

Introduction: Few studies have investigated how neuroinflammation early in the disease course may affect Alzheimer's disease (AD) progression over time despite evidence that neuroinflammation is associated with AD.

Methods: Research participants with cerebrospinal fluid (CSF) biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included in this study. Cox models were used to investigate whether baseline CSF neuroinflammation was associated with incident mild cognitive impairment (MCI) or AD.

Selective atrophy of the cervical enlargement in whole spinal cord MRI of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a deadly neurodegenerative disorder affecting motor neurons in the spinal cord and brain. Studies have reported on atrophy within segments of the cervical cord, but we are not aware of previous investigations of the whole spinal cord. Herein we present our findings from a 3T MRI study involving 32 subjects (15 ALS participants and 17 healthy controls) characterizing cross-sectional area along the entire cord.

The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic.

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other "sickness behavior"-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven 'Pre-Pandemic' and fifteen 'Pandemic' datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies.

Neuroimmune signatures in chronic low back pain subtypes.

We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g.

A Comparative Analysis of Online Versus in-Person Opioid Overdose Awareness and Reversal Training for First-Year Medical Students.

Physicians trained in opioid use disorder (OUD) harm reduction can mitigate opioid overdose deaths by prescribing naloxone and educating patients about its use. Unfortunately, many physicians possess OUD stigma. Training during medical school presents an opportunity to reduce OUD stigma and improve opioid overdose reversal knowledge.

[C]PBR28 radiotracer kinetics are not driven by alterations in cerebral blood flow.

The positron emission tomography (PET) radiotracer [C]PBR28 has been increasingly used to image the translocator protein (TSPO) as a marker of neuroinflammation in a variety of brain disorders. Interrelatedly, similar clinical populations can also exhibit altered brain perfusion, as has been shown using arterial spin labelling in magnetic resonance imaging (MRI) studies. Hence, an unsolved debate has revolved around whether changes in perfusion could alter delivery, uptake, or washout of the radiotracer [C]PBR28, and thereby influence outcome measures that affect interpretation of TSPO upregulation.

Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults.

CNS inflammation is a key factor in Alzheimer's Disease (AD), but its relation to pathological Aβ, tau, and APOE4 is poorly understood, particularly prior to the onset of cognitive symptoms. To better characterize early relationships between inflammation, APOE4, and AD pathology, we assessed correlations between cerebrospinal fluid (CSF) inflammatory markers and brain levels of Aβ and tau in cognitively normal older adults. Each participant received a lumbar puncture to collect and quantify CSF levels of TNFα, IL-6, IL-8, and IL-10, a T1-weighted MRI, and PET scanning with [F]flortaucipir (FTP; n = 57), which binds to tau tangles and/or [F]florbetapir (FBP; n = 58), which binds to Aβ.

Thalamic neurometabolite alterations in patients with knee osteoarthritis before and after total knee replacement.

The weak association between disability levels and "peripheral" (ie, knee) findings suggests that central nervous system alterations may contribute to the pathophysiology of knee osteoarthritis (KOA). Here, we evaluated brain metabolite alterations in patients with KOA, before and after total knee arthroplasty (TKA), using 1H-magnetic resonance spectroscopy (MRS). Thirty-four presurgical patients with KOA and 13 healthy controls were scanned using a PRESS sequence (TE = 30 ms, TR = 1.

Thalamic neuroinflammation as a reproducible and discriminating signature for chronic low back pain.

Using positron emission tomography, we recently demonstrated elevated brain levels of the 18 kDa translocator protein (TSPO), a glial activation marker, in chronic low back pain (cLBP) patients, compared to healthy controls (HCs). Here, we first sought to replicate the original findings in an independent cohort (15 cLBP, 37.8 ± 12.

Associations between Vascular Function and Tau PET Are Associated with Global Cognition and Amyloid.

Tau pathology and vascular dysfunction are important contributors to Alzheimer's disease (AD), but vascular-tau associations and their effects on cognition are poorly understood. We investigated these associations in male and female humans by conducting voxelwise comparisons between cerebral blood flow (CBF) and tau positron emission tomography (PET) images in independent discovery [cognitively normal (CN), 19; mild cognitive impairment (MCI) risk, 43; MCI, 6] and replication (CN,73; MCI, 45; AD, 20) cohorts. In a subgroup, we assessed relationships between tau and soluble platelet-derived growth factor β (sPDGFRβ), a CSF marker of pericyte injury.

Inpainting as a Technique for Estimation of Missing Voxels in Brain Imaging.

Issues with model fitting (i.e. suboptimal standard deviation, linewidth/full-width-at-half-maximum, and/or signal-to-noise ratio) in multi-voxel MRI spectroscopy, or chemical shift imaging (CSI) can result in the significant loss of usable voxels.

Extra-Axial Inflammatory Signal in Parameninges in Migraine with Visual Aura.

Objective: Cortical spreading depression (CSD) underlies the neurobiology of migraine with aura (MWA). Animal studies reveal networks of microvessels linking brain-meninges-bone marrow. CSD activates the trigeminovascular system, evoking a meningeal inflammatory response.

Striatal hypofunction as a neural correlate of mood alterations in chronic pain patients.

Background: Chronic pain and mood disorders share common neuroanatomical substrates involving disruption of the reward system. Although increase in negative affect (NA) and decrease in positive affect (PA) are well-known factors complicating the clinical presentation of chronic pain patients, our understanding of the mechanisms underlying the interaction between pain and PA/NA remains limited. Here, we used a validated task probing behavioral and neural responses to monetary rewards and losses in conjunction with functional magnetic resonance imaging (fMRI) to test the hypothesis that dysfunction of the striatum, a key mesolimbic structure involved in the encoding of motivational salience, relates to mood alterations comorbid with chronic pain.

In-vivo imaging of neuroinflammation in veterans with Gulf War illness.

Gulf War Illness (GWI) is a chronic disorder affecting approximately 30% of the veterans who served in the 1991 Gulf War. It is characterised by a constellation of symptoms including musculoskeletal pain, cognitive problems and fatigue. The cause of GWI is not definitively known but exposure to neurotoxicants, the prophylactic use of pyridostigmine bromide (PB) pills, and/or stressors during deployment have all been suspected to play some pathogenic role.

Imaging of neuroinflammation in migraine with aura: A [C]PBR28 PET/MRI study.

Objective: To determine if migraine with aura is associated with neuroinflammation, which has been suggested by preclinical models of cortical spreading depression (CSD) as well as imaging of human pain conditions.

Methods: Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [C]PBR28, a radioligand that binds to the 18 kDa translocator protein, a marker of glial activation. Standardized uptake value ratio (SUVR) was compared between groups, and regressed against clinical variables, using region of interest and whole-brain voxelwise analyses.

PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia.

Background: Patients with schizophrenia (SCZ) experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymes that regulate cognitive circuitry; however, the role of HDACs in cognitive disorders, including SCZ, remains unknown in humans. We previously determined that HDAC2 mRNA levels were lower in dorsolateral prefrontal cortex (DLPFC) tissue from donors with SCZ compared with controls.

Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation.

Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes.

Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients.

Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. Here, we show that patients suffering from a common chronic pain disorder (lumbar radiculopathy), compared with healthy volunteers, exhibit elevated levels of the neuroinflammation marker 18 kDa translocator protein, in both the neuroforamina (containing dorsal root ganglion and nerve roots) and spinal cord.

PET Imaging of Human Brown Adipose Tissue with the TSPO Tracer [C]PBR28.

Purpose: Brown adipose tissue (BAT) in adult humans has been recently rediscovered and intensively investigated as a new potential therapeutic target for obesity and type 2 diabetes (T2D). However, reliable assessment of BAT mass in vivo represents a considerable challenge. The purpose of this investigation is to demonstrate for the first time that human BAT depots can be imaged with a translocator protein (TSPO)-specific positron emission tomography (PET) tracer [C]PBR28 under thermoneutral conditions.