Microglial responses partially mediate the effect of Aβ on cognition in Alzheimer's disease.

Introduction: Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aβ) deposition. This study aimed to investigate the effects of Aβ and microglial responses on global cognitive impairment.

Methods: In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent C-PK11195 and C-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up.

Performance on complex memory tests is associated with β-amyloid in individuals at risk of developing Alzheimer's disease.

The pathophysiological development of Alzheimer's disease (AD) begins in the brain years before the onset of clinical symptoms. The accumulation of beta-amyloid (Aβ) is thought to be the first cortical pathology to occur. Carrying one apolipoprotein E (APOE) ε4 allele increases the risk of developing AD at least 2-3 times and is associated with earlier Aβ accumulation.

Sertraline treatment influences [F]FE-PE2I PET imaging for Parkinsonism.

Background: The dopamine transporter (DaT) PET ligand [F]FE-PE2I is used to aid the diagnosis of Parkinson's disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [F]FE-PE2I binding due to sertraline's high affinity for DaT.

Methods: We rescanned the four patients with [F]FE-PE2I PET after a 5-day sertraline pause.

Asymmetric amyloid deposition in preclinical Alzheimer's disease: A PET study.

Introduction: The typical spatial pattern of amyloid-β (Aβ) in diagnosed Alzheimer's disease (AD) is that of a symmetrical hemispheric distribution. However, Aβ may be asymmetrically distributed in early stages of AD. Aβ distribution on PET has previously been explored in MCI and AD, but it has yet to be directly investigated in preclinical AD (pAD).

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

Background: The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables.

Materials And Methods: This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery.

Regional and interindividual relationships between cerebral perfusion and oxygen metabolism.

Quantitative measurements of resting cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO) show large between-subject and regional variability, but the relationships between CBF and CMRO measurements regionally and globally are not fully established. Here, we investigated the between-subject and regional associations between CBF and CMRO measures with independent and quantitative PET techniques. We included resting CBF and CMRO measurements from 50 healthy volunteers (aged 22-81 yr), and calculated the regional and global values of oxygen delivery (Do) and oxygen extraction fraction (OEF).

Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial.

Background: Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine.

Quantitative and clinical impact of MRI-based attenuation correction methods in [F]FDG evaluation of dementia.

Background: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a promising diagnostic imaging tool for the diagnosis of dementia, as PET can add complementary information to the routine imaging examination with MRI. The purpose of this study was to evaluate the influence of MRI-based attenuation correction (MRAC) on diagnostic assessment of dementia with [F]FDG PET. Quantitative differences in both [F]FDG uptake and z-scores were calculated for three clinically available (DixonNoBone, DixonBone, UTE) and two research MRAC methods (UCL, DeepUTE) compared to CT-based AC (CTAC).

Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study.

Objective: Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD).

Methods: Six clinically probable AD and 20 MCI subjects had inflammation (C-(R)-PK11195), amyloid (C-PiB) and tau (F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses.

Regional cerebral effects of ketone body infusion with 3-hydroxybutyrate in humans: Reduced glucose uptake, unchanged oxygen consumption and increased blood flow by positron emission tomography. A randomized, controlled trial.

Ketone bodies are neuroprotective in neurological disorders such as epilepsy. We randomly studied nine healthy human subjects twice-with and without continuous infusion of 3-hydroxybutyrate-to define potential underlying mechanisms, assessed regionally (parietal, occipital, temporal, cortical grey, and frontal) by PET scan. During 3-hydroxybutyrate infusions concentrations increased to 5.

Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours: study protocol for a randomised controlled trial.

Introduction: During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after phenylephrine administration, but unaltered by ephedrine administration. These findings may be explained by different effects of phenylephrine and ephedrine on the cerebral microcirculation, in particular the capillary transit-time heterogeneity, which determines oxygen extraction efficacy.

Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease.

See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-β have a greatly increased risk of progressing to Alzheimer's disease.

Sex differences of human cortical blood flow and energy metabolism.

Brain energy metabolism is held to reflect energy demanding processes in neuropil related to the density and activity of synapses. There is recent evidence that men have higher density of synapses in temporal cortex than women. One consequence of these differences would be different rates of cortical energy turnover and blood flow in men and women.

Washout allometric reference method (WARM) for parametric analysis of [(11)C]PIB in human brains.

Rapid clearance and disappearance of a tracer from the circulation challenges the determination of the tracer's binding potentials in brain (BP ND) by positron emission tomography (PET). This is the case for the analysis of the binding of radiolabeled [(11)C]Pittsburgh Compound B ([(11)C]PIB) to amyloid-β (Aβ) plaques in brain of patients with Alzheimer's disease (AD). To resolve the issue of rapid clearance from the circulation, we here introduce the flow-independent Washout Allometric Reference Method (WARM) for the analysis of washout and binding of [(11)C]PIB in two groups of human subjects, healthy aged control subjects (HC), and patients suffering from AD, and we compare the results to the outcome of two conventional analysis methods.

Blood-brain transfer of Pittsburgh compound B in humans.

In the labeled form, the Pittsburgh compound B (2-(4'-{N-methyl-[(11)C]}methyl-aminophenyl)-6-hydroxy-benzothiazole, [(11)C]PiB), is used as a biomarker for positron emission tomography (PET) of brain β-amyloid deposition in Alzheimer's disease (AD). The permeability of [(11)C]PiB in the blood-brain barrier is held to be high but the permeability-surface area product and extraction fractions in patients or healthy volunteers are not known. We used PET to determine the clearance associated with the unidrectional blood-brain transfer of [(11)C]PiB and the corresponding cerebral blood flow rates in frontal lobe, whole cerebral cortex, and cerebellum of patients with Alzheimer's disease and healthy volunteers.

Low Residual CBF Variability in Alzheimer's Disease after Correction for CO(2) Effect.

We tested the claim that inter-individual CBF variability in Alzheimer's disease (AD) is substantially reduced after correction for arterial carbon dioxide tension (PaCO(2)). Specifically, we tested whether the variability of CBF in brain of patients with AD differed significantly from brain of age-matched healthy control subjects (HC). To eliminate the CO(2)-induced variability, we developed a novel and generally applicable approach to the correction of CBF for changes of PaCO(2) and applied the method to positron emission tomographic (PET) measures of CBF in AD and HC groups of subjects.

Brain energy metabolism and blood flow differences in healthy aging.

Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors find decreases of both CBF and CMRO(2) but increased OEF, while others find no change, and yet other find divergent changes. In this reanalysis of previously published results from positron emission tomography of healthy volunteers, we determined CMRO(2) and CBF in 66 healthy volunteers aged 21 to 81 years.

Glucose metabolism in small subcortical structures in Parkinson's disease.

Objectives: Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PET) cameras. However, the high-resolution research tomograph (HRRT) PET system has a resolution of 2 mm, sufficient for the investigation of important structures such as the pallidum and thalamic subnuclei.

Variable ATP yields and uncoupling of oxygen consumption in human brain.

The distribution of brain oxidative metabolism values among healthy humans is astoundingly wide for a measure that reflects normal brain function and is known to change very little with most changes of brain function. It is possible that the part of the oxygen consumption rate that is coupled to ATP turnover is the same in all healthy human brains, with different degrees of uncoupling explaining the variability of total oxygen consumption among people. To test the hypothesis that about 75% of the average total oxygen consumption of human brains is common to all individuals, we determined the variability in a large group of normal healthy adults.

Subcortical elevation of metabolism in Parkinson's disease--a critical reappraisal in the context of global mean normalization.

In a recent issue of NeuroImage, we presented evidence that biased global mean (GM) normalization of brain PET data can generate the appearance of subcortical foci with relative hypermetabolism in patients with Parkinson's disease (PD), and other degenerative disorders. In a commentary to our article, Ma and colleagues presented a study seeking to establish that a pattern of widespread hypermetabolism, known as the Parkinson's disease related pattern (PDRP) is a genuine metabolic feature of PD. In the present paper, we respond to the arguments presented by Ma et al.

Data-driven intensity normalization of PET group comparison studies is superior to global mean normalization.

Background: Global mean (GM) normalization is one of the most commonly used methods of normalization in PET and SPECT group comparison studies of neurodegenerative disorders. It requires that no between-group GM difference is present, which may be strongly violated in neurodegenerative disorders. Importantly, such GM differences often elude detection due to the large intrinsic variance in absolute values of cerebral blood flow or glucose consumption.

Artefactual subcortical hyperperfusion in PET studies normalized to global mean: lessons from Parkinson's disease.

Aim: Recent studies of Parkinson's disease (PD) report subcortical increases of cerebral blood flow (CBF) or cerebral metabolic rate of glucose (CMRglc), after conventional normalization to the global mean. However, if the global mean CBF or CMRglc is decreased in the PD group, this normalization necessarily generates artificial relative increases in regions unaffected by the disease. This potential bias may explain the reported subcortical increases in PD.