Brain Fluorodeoxyglucose Positron Emission Tomography Research Articles

Impaired Self-Awareness in Parkinson's and Huntington's Diseases: A Literature Review of Neuroimaging Correlates.

Little is known about the brain correlates of anosognosia or unawareness of disease in Parkinson's Disease (PD) and Huntington's Disease (HD). The presence of unawareness or impaired self-awareness (ISA) of illness has profound implications for patients and their caregivers; therefore, studying awareness and its brain correlates should be considered a key step towards developing effective recognition and management of this symptom as it offers a window into the mechanism of self-awareness and consciousness as critical components of the human cognition. We reviewed research studies adopting MRI or other in vivo neuroimaging technique to assess brain structural and/or functional correlates of unawareness in PD and HD across different cognitive and motor domains. Studies adopting task or resting-state functional magnetic resonance imaging, and/or 18-F fluorodeoxyglucose positron emission tomography brain imaging and/or magnetic resonance imaging structural measures were considered. Only six studies investigating neuroimaging features of unawareness in PD and two in HD were identified; there was great heterogeneity in the clinical characteristics of the study participants, domain of unawareness investigated, method of unawareness assessment, and neuroimaging technique used. Nevertheless, some data converge in identifying regions of the salience and frontoparietal networks to be associated with unawareness in PD patients. In HD, the few data are affected by the variability in the severity of motor symptoms. Further studies are needed to better understand the mechanisms and brain correlates of unawareness in PD and HD; in addition, the use of dopaminergic medications should be carefully considered.

Patient-specific brain fluorodeoxyglucose positron emission tomography can detect the first effects of combination antiretroviral therapy in patient with HIV infection

Patient-specific brain fluorodeoxyglucose positron emission tomography can detect the first effects of combination antiretroviral therapy in patient with HIV infection

Semiquantitative analysis of cerebral [18F]FDG-PET uptake in pediatric patients

BackgroundGlycolytic metabolism in the brain of pediatric patients, imaged with [18F] fluorodeoxyglucose-positron emission tomography (FDG-PET) is incompletely characterized.ObjectiveThe purpose of the current study was to characterize [18F]FDG-PET brain uptake in a large sample of pediatric patients with non-central nervous system diseases as an alternative to healthy subjects to evaluate changes at different pediatric ages.Materials and MethodsSeven hundred ninety-five [18F]FDG-PET examinations from children < 18 years of age without central nervous system diseases were included. Each brain image was spatially normalized, and the standardized uptake value (SUV) was obtained. The SUV and the SUV relative to different pseudo-references were explored as a function of age.ResultsAt all evaluated ages, the occipital lobe showed the highest [18F]FDG uptake (0.27 ± 0.04 SUV/year), while the parietal lobe and brainstem had the lowest uptake (0.17 ± 0.02 SUV/year, for both regions). An increase [18F]FDG uptake was found for all brain regions until 12 years old, while no significant uptake differences were found between ages 13 (SUV = 5.39) to 17 years old (SUV = 5.52) (P < 0.0001 for the whole brain). A sex dependence was found in the SUVmean for the whole brain during adolescence (SUV 5.04–5.25 for males, 5.68–5.74 for females, P = 0.0264). Asymmetries in [18F]FDG uptake were found in the temporal and central regions during infancy.ConclusionsBrain glycolytic metabolism of [18F]FDG, measured through the SUVmean, increased with age until early adolescence (< 13 years old), showing differences across brain regions. Age, sex, and brain region influence [18F]FDG uptake, with significant hemispheric asymmetries for temporal and central regions.Graphical

Brain FDG-PET correlates of saccadic disorders in early PSP.

New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP.

Longitudinal brain and skeletal muscle FDG-PET changes in people with stiff person syndrome spectrum disorders (P4-5.021)

<h3>Objective:</h3> To describe changes in fluorodeoxyglucose positron emission tomography (FDG-PET) findings in the brain and muscles of individuals with stiff person syndrome spectrum disorders (SPSD) longitudinally. <h3>Background:</h3> SPSD includes multiple clinical phenotypes that rarely can be paraneoplastic in origin. An FDG-PET scan is frequently obtained as part of the malignancy work-up, and abnormal metabolic activity unrelated to malignancy has been shown to occur in both the brain and skeletal muscles of patients with SPSD. However, it is unclear if such findings persist or change over time. <h3>Design/Methods:</h3> A retrospective study was performed of patients with SPSD who were seen at Johns Hopkins SPS Center from 2009 to March 2022, with at least two FDG-PET studies in the medical record with source images of sufficient quality for comparison. Quantitative data was extracted from dedicated brain FDG-PET scans using NeuroQ™, which calculates Z-scores of 47 brain regions compared to healthy controls. Body FDG-PET scans will be reviewed qualitatively by a blinded nuclear medicine radiologist to detect the presence and pattern of hypermetabolism in skeletal muscle. Patients’ clinical characteristics, including type of treatment, will be correlated with PET data. <h3>Results:</h3> Out of 98 SPSD patients who underwent an FDG-PET scan, 10 were identified that met inclusion criteria. Median age at time of SPSD onset was 51±15.8 years, 60% were males, and 60% were black. Mean duration from symptom onset to first FDG-PET scan was 0.78±0.62 years. The majority of patients had SPS-plus phenotype. All patients were seropositive for an SPSD-associated antibody and received an immune therapy. Preliminary data demonstrate that all patients had at least 1 region of dysmetabolism on initial brain scan, and at least 3 regions on follow-up. <h3>Conclusions:</h3> We will present longitudinal metabolic changes in brain and body FDG-PET scans of patients with SPSD, and determine if any changes observed are associated with clinical characteristics. <b>Disclosure:</b> Dr. Roman has nothing to disclose. The institution of Dr. Wang has received research support from Genentech. Dr. Sadaghiani has nothing to disclose. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Newsome has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Newsome has received research support from Biogen. The institution of Dr. Newsome has received research support from Genentech/Roche. The institution of Dr. Newsome has received research support from Department of Defense. The institution of Dr. Newsome has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Newsome has received research support from National MS Society. The institution of Dr. Newsome has received research support from The Stiff Person Syndrome Research Foundation. Dr. Newsome has received personal compensation in the range of $5,000-$9,999 for serving as a Clinical adjudication committee member for clinical trial with medDay Pharmaceuticals. Dr. Newsome has received personal compensation in the range of $10,000-$49,999 for serving as a Lead PI for Clinical Trial with Roche.

Accuracy of predicting surgical outcomes using interictal electrical source imaging in patients with MRI-negative intractable epilepsy

ObjectiveWe investigated the accuracy of interictal electrical source imaging (II-ESI) in localizing the epileptogenic zone in MRI-negative epilepsy patients who underwent epilepsy surgery. We also aimed to compare II-ESI's utility with other presurgical investigations and its role in guiding intracranial electroencephalography (iEEG) planning. MethodsWe retrospectively reviewed the medical records of patients with operated MRI-negative intractable epilepsy at our center between 2010 and 2016. All patients underwent video electroencephalography (EEG) monitoring, high-resolution MRI, 18 fluorodeoxyglucose positron emission tomography (FDG-PET) scans, ictal single-photon emission computed tomography (SPECT) and intracranial EEG (iEEG) monitoring. We computed II-ESI following the visual identification of interictal spikes, and outcomes were determined using Engel’s classification at 6 months after surgery. ResultsAmong 21 operated MRI-negative intractable epilepsy patients, 15 had sufficient data for II-ESI analysis. Of these, nine patients (60%) showed favorable outcomes corresponding to Engle's classification I and II. The localization accuracy of II-ESI was 53%, which was not significantly different from those of FDG-PET and ictal SPECT (47% and 45%, respectively). Among the patients, iEEG did not cover the areas suggested by II-ESIs in seven cases (47%). In two of those patients (29%), the regions indicated by II-ESIs were not resected, resulting in poor surgical outcomes. ConclusionThis study demonstrates that the localization accuracy of II-ESI was comparable to ictal SPECT and the brain FDG-PET scan. II-ESI is a simple, noninvasive method for evaluating the epileptogenic zone and guiding iEEG planning in patients with MRI-negative epilepsy.

Perivascular Space Predicts Brain Hypometabolism of Individuals with Underlying Amyloid Pathology.

Reduced signal on fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valid proxy for neurodegeneration in Alzheimer's disease (AD). Perivascular space (PVS) is believed to be associated with AD pathology and cognitive decline. This study aimed to investigate the associations of PVS with FDG-PET and cognitive performance based on the burden of amyloid pathology. We used magnetic resonance imaging (MRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). MRI-visible PVS in basal ganglia (BG) and centrum semi-oval (CSO) were visually classified as: none/mild, moderate or frequent/severe. The association of PVS with brain FDG-PET was explored based on the burden of amyloid pathology, where a cerebrospinal fluid (CSF) t-tau/Aβ42 with the ratio≥0.27 was defined as high amyloid pathology. Moreover, the relationships between PVS and cognitive performance variables (ADNI-MEM and ADNI-EF) were studied. For participants with higher tau/Aβ42 ratio, CSO-PVS severity was independently associated with lower FDG-PET. There were significant interaction effects between moderate or frequent/severe CSO-PVS and time on FDG decline in people with high amyloid pathology. The interaction between CSO-PVS and time (follow-up) was consistently associated with ADNI-MEM and ADNI-EF decline in individuals with high amyloid pathology. The study established the differential utility of PVS in BG and CSO for predicting brain metabolism. These findings suggest that CSO-PVS serves as a contributing factor to brain metabolism and cognitive decline associated with amyloid pathology.

Clinical and metabolic imaging features of late-onset and early-onset posterior cortical atrophy.

Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and 18 fluoro-deoxy-glucose positron emission tomography (FDG-PET) features of LO and EO posterior cortical atrophy (LO_PCA, EO_PCA), the visual variant of Alzheimer's disease (AD), were compared. LO_PCA patients were also compared with a group of patients with LO typical AD (tAD). Thirty-seven LO_PCA patients (onset age ≥ 65 years), 29 EO_PCA patients and 40 tAD patients who all underwent a standard neuropsychological battery were recruited; PCA patients were also assessed for the presence of posterior signs and symptoms. Brain FDG-PET was available in 32 LO_PCA cases, 23 EO_PCA cases and all tAD cases, and their scans were compared with scans from 30 healthy elderly controls. Within the entire PCA sample FDG uptake was also correlated with age at onset as a continuous variable. The main difference between the two PCA groups was a higher prevalence of Bálint-Holmes symptoms in EO cases, which was associated with the presence of severe bilateral occipito-temporo-parietal hypometabolism, whilst LO_PCA patients showed reduction of FDG uptake mainly in the right posterior regions. The latter group also showed mesial temporal hypometabolism, similarly to the tAD group, although with a right rather than left lateralization. Correlation analysis confirmed the association between older age and decreased limbic metabolism and between younger age and decreased left parietal metabolism. The major involvement of the temporal cortex in LO cases and of the parietal cortex in EO cases reported previously within the AD spectrum holds true also for the visual variant of AD.

Correlation between fluorodeoxyglucose positron emission tomography brain hypometabolism and posttraumatic stress disorder symptoms in temporal lobe epilepsy.

The relationship between posttraumatic stress disorder (PTSD) and focal epilepsy is poorly understood. It has been hypothesized that there is a complex and reciprocal potential reinforcement of the symptoms of each condition. In this study, we investigated whether there are PTSD‐specific brain changes in temporal lobe epilepsy (TLE). Brain fluorodeoxyglucose positron emission tomography (PET) metabolism was compared between controls and two groups of TLE patients: one group of 15 patients fulfilling the criteria for a potential diagnosis of PTSD (TLE‐PTSD+), another group of 24 patients without a diagnosis of PTSD (TLE‐PTSD‐), and a group of 30 healthy control participants. We compared the differences in brain PET metabolism among these three groups, and we studied their correlations with interictal and peri‐ictal scales of PTSD symptoms. TLE‐PTSD+ patients showed more significant hypometabolism involving right temporal and right orbitofrontal cortex in comparison to TLE‐PTSD‐ patients and healthy subjects. Moreover, degree of reduced metabolism in these brain areas correlated with interictal and peri‐ictal PTSD questionnaire scores. PTSD in temporal epilepsy is associated with specific changes in neural networks, affecting limbic and paralimbic structures. This illustrates the close intertwining of epileptogenic and psychogenic processes in these patients.

Prediction of post-stroke cognitive impairment using brain FDG PET: deep learning-based approach

Post-stroke cognitive impairment can affect up to one third of stroke survivors. Since cognitive function greatly contributes to patients' quality of life, an objective quantitative biomarker for early prediction of dementia after stroke is required. We developed a deep-learning (DL)-based signature using positron emission tomography (PET) to objectively evaluate cognitive decline in patients with stroke. We built a DL model that differentiated Alzheimer's disease (AD) from normal controls (NC) using brain fluorodeoxyglucose (FDG) PET from the Alzheimer's Disease Neuroimaging Initiative database. The model was directly transferred to a prospectively enrolled cohort of patients with stroke to differentiate patients with dementia from those without dementia. The accuracy of the model was evaluated by the area under the curve values of receiver operating characteristic curves (AUC-ROC). We visualized the distribution of DL-based features and brain regions that the model weighted for classification. Correlations between cognitive signature from the DL model and clinical variables were evaluated, and survival analysis for post-stroke dementia was performed in patients with stroke. The classification of AD vs. NC subjects was performed with AUC-ROC of 0.94 (95% confidence interval [CI], 0.89-0.98). The transferred model discriminated stroke patients with dementia (AUC-ROC = 0.75). The score of cognitive decline signature using FDG PET was positively correlated with age, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and negatively correlated with body mass index in patients with stroke. We found that the cognitive decline score was an independent risk factor for dementia following stroke (hazard ratio, 10.90; 95% CI, 3.59-33.09; P < 0.0001) after adjustment for other key variables. The DL-based cognitive signature using FDG PET was successfully transferred to an independent stroke cohort. It is suggested that DL-based cognitive evaluation using FDG PET could be utilized as an objective biomarker for cognitive dysfunction in patients with cerebrovascular diseases.

Value of [18F]-FDG positron emission tomography in patients with recurrent glioblastoma receiving bevacizumab.

BackgroundTreatment of recurrent glioblastoma (GBM) with bevacizumab can induce MRI changes that confound the determination of progression. We sought to determine the value of [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in GBM patients receiving bevacizumab at the time of suspected progression and, thereby, its utility as a potential prognostic adjunct in progressive disease.MethodsThis retrospective study included patients who underwent brain FDG PET within 4 weeks of receiving bevacizumab for recurrent GBM with suspected progression. Volumes-of-interest were placed over the reference lesion with measurement of maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), metabolic tumor volume, total lesion glycolysis (TLG), and tumor-to-normal contralateral white matter ratios (TNR-WM). Tumors were additionally categorized as non-avid or avid based on qualitative FDG uptake. Associations between baseline variables and overall survival (OS) were examined using univariable and multivariable Cox proportional hazards regression, with P < .05 considered significant.ResultsThirty-one patients were analyzed. Qualitative FDG uptake was significantly associated with OS (P = .03), with a median OS of 9.0 months in non-avid patients versus 4.5 months in avid patients. SUVmax, SUVpeak, TNR-WM, and TLG were significantly associated with OS (P < .001, TLG: P = .009). FDG avidity and SUVmax remained significantly associated with OS (P = .046 and .048, respectively) in the multivariable analysis including age, KPS, and MGMT status. Dichotomizing patients using an SUVmax cutoff of 15.3 was associated with OS (adjusted P = .048).ConclusionFDG PET is a promising imaging tool to further stratify prognosis in recurrent GBM patients on antiangiogenic therapy.

Scaled Subprofile Modeling and Convolutional Neural Networks for the Identification of Parkinson's Disease in 3D Nuclear Imaging Data.

Over the last years convolutional neural networks (CNNs) have shown remarkable results in different image classification tasks, including medical imaging. One area that has been less explored with CNNs is Positron Emission Tomography (PET). Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a PET technique employed to obtain a representation of brain metabolic function. In this study we employed 3D CNNs in FDG-PET brain images with the purpose of discriminating patients diagnosed with Parkinson's disease (PD) from controls. We employed Scaled Subprofile Modeling using Principal Component Analysis as a preprocessing step to focus on specific brain regions and limit the number of voxels that are used as input for the CNNs, thereby increasing the signal-to-noise ratio in our data. We performed hyperparameter optimization on three CNN architectures to estimate the classification accuracy of the networks on new data. The best performance that we obtained was and area under the receiver operating characteristic curve on the test set. We believe that, with larger datasets, PD patients could be reliably distinguished from controls by FDG-PET scans alone and that this technique could be applied to more clinically challenging tasks, like the differential diagnosis of neurological disorders with similar symptoms, such as PD, Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA).

Propofol Anesthesia Alters Spatial and Topologic Organization of Rat Brain Metabolism.

Loss of consciousness during anesthesia reduces local and global rate of cerebral glucose metabolism. Despite this, the influence of gradual anesthetic-induced changes on consciousness across the entire brain metabolic network has barely been studied. The purpose of the present study was to identify specific cerebral metabolic patterns characteristic of different consciousness/anesthesia states induced by intravenous anesthetic propofol. At various times, 20 Sprague-Dawley adult rats were intravenously administered three different dosages of propofol to induce different anesthetic states: mild sedation (20 mg · kg · h), deep sedation (40 mg · kg · h), and deep anesthesia (80 mg · kg · h). Using [F]fluorodeoxyglucose positron emission tomography brain imaging, alterations in the spatial pattern of metabolic distribution and metabolic topography were investigated by applying voxel-based spatial covariance analysis and graph-theory analysis. Evident reductions were found in baseline metabolism along with altered metabolic spatial distribution during propofol-induced anesthesia. Moreover, graph-theory analysis revealed a disruption in global and local efficiency of the metabolic brain network characterized by decreases in metabolic connectivity and energy efficiency during propofol-induced deep anesthesia (mild sedation global efficiency/local efficiency = 0.6985/0.7190, deep sedation global efficiency/local efficiency = 0.7444/0.7875, deep anesthesia global efficiency/local efficiency = 0.4498/0.6481; mild sedation vs. deep sedation, global efficiency: P = 0.356, local efficiency: P = 0.079; mild sedation vs. deep anesthesia, global efficiency: P < 0.0001, local efficiency: P < 0.0001; deep sedation vs. deep anesthesia, global efficiency: P < 0.0001, local efficiency: P < 0.0001). A strong spatial correlation was also found between cerebral metabolism and metabolic connectivity strength, which decreased significantly with deepening anesthesia level (correlation coefficients: mild sedation, r = 0.55, deep sedation, r = 0.47; deep anesthesia, r = 0.23; P < 0.0001 between the sedation and deep anesthesia groups). The data revealed anesthesia-related alterations in spatial and topologic organization of metabolic brain network, as well as a close relationship between metabolic connectivity and cerebral metabolism during propofol anesthesia. These findings may provide novel insights into the metabolic mechanism of anesthetic-induced loss of consciousness.

Two distinct pathological substrates associated with MMSE-pentagons item deficit in DLB and AD

IntroductionDementia with Lewy Bodies (DLB) is characterized by a prominent deficit in visuospatial abilities. Visuospatial impairment is also detectable in the course of Alzheimer's dementia (AD). However, visuospatial impairment presents some differences in these two conditions, suggesting pathological involvement of distinct brain circuits. Recent studies applied a new method to score the Mini Mental State Examination (MMSE) pentagon copy subtest, namely the Qualitative Scoring Pentagon Test (QSPT), which is a sensitive measure of visuospatial abilities. Using [18F]fluorodeoxy-glucose positron emission tomography (FDG-PET), we assessed the relationship between in vivo brain metabolic dysfunction and visuospatial deficits, in terms of QSPT total value, in DLB and AD. Materials and methodsSixty Patients were diagnosed as DLB (n = 35) and AD (n = 25) dementia according with the standard research diagnostic criteria. Each patient underwent a FDG-PET scan as support for the final diagnosis. Patients underwent an extended neuropsychological evaluation, including MMSE, language, memory, executive functions and visuospatial abilities tests. The MMSE QSPT scoring was calculated following the methods by Caffarra et al. (2013). Offline voxel-wise correlation analysis between QSPT total scores and FDG-PET brain metabolism was then performed, correcting for MMSE, sex and disease duration. ResultsBoth groups presented reduced visuospatial performances, as assessed by QSPT scores. DLB compared to AD showed a statistically significant difference in QSPT rotation parameter (p = 0.022). In DLB, worse performance at QSPT total score, i.e. more severe visuospatial impairment, correlated with brain occipital hypometabolism (i.e. lateral occipital cortex, calcarine cortex, fusiform and lingual gyri). In AD, worse performance at QSPT total score correlated with brain hypometabolism in the right parietal cortex (i.e. superior and inferior parietal cortex and angular gyrus). DiscussionThese findings reveal that visuospatial deficits may derive from distinct brain alterations in AD and DLB. We propose that the inabilities to perform correctly the QSPT task is related to altered visuoperceptual process in DLB, and visuospatial process in AD. This is consistent with our results showing hypometabolism in brain system related to visuoperceptual processing, namely the occipital cortex in DLB, and visuospatial processing, namely parietal cortex in AD.

Metabolic patterns across core features in dementia with lewy bodies.

To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern. Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core-feature-specific patterns controlling for the main confounding variables (Mini-Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE-sensitive map. Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral-frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto-occipital cortex, precuneus, and ventrolateral-frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral-parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum. Regions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a close clinical-imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. Ann Neurol 2019;85:715-725.

Abnormal metabolic brain network associated with Parkinson's disease: replication on a new European sample.

The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson's disease (PD): Parkinson's disease-related pattern (PDRP), using network analysis of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients. Twenty PD patients (age 70.1±7.8years, Movement Disorder Society Unified Parkinson's Disease Motor Rating Scale (MDS-UPDRS-III) 38.3±12.2; disease duration 4.3±4.1years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification. The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (p<0.0001) and correlated positively with patients' clinical score (MDS-UPDRS-III, p=0.03). Additionally, its topography agrees well with the original PDRP (p<0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85-90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP. PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression.

Metabolic Activity Value in the Posterior Cingulate Cortex Using F-18 Fluorodeoxyglucose Positron Emission Tomography Brain to Predict the Severity of Alzheimer's.

Alzheimer's disease (AD) is a type of dementia which is known as one of a major problem in elderly. Clinicians commonly use mini-mental state examination (MMSE) score to determine the severity of cognitive decline, but MMSE has some limitations such as more subjective, influenced by age, educational degree, and local culture. F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) can be used to assess the process of glucose metabolism in posterior cingulate cortex (PCC) area which endures a central role in supporting cognitive function directly. The purpose of this study is to observe a correlation between metabolic activity value of PCC and MMSE score in predicting the severity of AD. A cross-sectional study was done to 30 subjects suspect AD disease with aged 60 years and older. Characteristic data including gender, age, and education, MMSE scoring by psychiatrist, and imaging of F-18 FDG PET were established. The results of correlation test between the value of FDG metabolic activity and MMSE score shows that the value of metabolic activity in the PCC area tends to increase along with the increase of MMSE score (rs = 0.411, P = 0.024). While from the results of multiple regression test with predictor variable consisting of F-18 FDG metabolic activity in the PCC, gender, age, education level, and the interaction between the metabolic activity of F-18 FDG at PCC and gender, a regression model was obtained. There is a significant correlation observed between the captured of F-18 FDG radioactivity with MMSE score in PCC area which can be used as a tool to predict the severity of AD.

Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd.

Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial.

Diabetes and hyperinsulinemia may be risk factors for Alzheimer's disease (AD). We conducted a pilot study of metformin, a medication efficacious in treating and preventing diabetes while reducing hyperinsulinemia, among persons with amnestic mild cognitive impairment (aMCI) with the goal of collecting preliminary data on feasibility, safety, and efficacy. Participants were 80 men and women aged 55 to 90 years with aMCI, overweight or obese, without treated diabetes. We randomized participants to metformin 1000 mg twice a day or matching placebo for 12 months. The co-primary clinical outcomes were changes from baseline to 12 months in total recall of the Selective Reminding Test (SRT) and the score of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). The secondary outcome was change in relative glucose uptake in the posterior cingulate-precuneus in brain fluorodeoxyglucose positron emission tomography. Change in plasma Aβ42 was an exploratory outcome. The mean age of participants was 65 years. Fifty percent of participants were women. The only baseline variable that was different between the arms was the ADAS-Cog. Metformin could not be tolerated by 7.5% of participants; 15% tolerated 500 mg/day, 35% tolerated 1000 mg/day, 32.5% tolerated 1500 mg/day, and only 10% tolerated the maximum dose. There were no serious adverse events related to metformin. The 7.5% of persons who did not tolerate metformin reported gastrointestinal symptoms. After adjusting for baseline ADAS-cog, changes in total recall of the SRT favored the metformin group (9.7±8.5 versus 5.3±8.5; p = 0.02). Differences for other outcomes were not significant. A larger trial seems warranted to evaluate the efficacy and cognitive safety of metformin in prodromal AD.

Factors Contributing to Speech Performance in Elderly Cochlear Implanted Patients: An FDG-PET Study: A Preliminary Study.

The purpose was to evaluate brain plasticity that contributes to speech performance after cochlear implantation (CI) in postlingual elderly (>60 years) patients. Fifteen elderly postlingual deaf patients who underwent preoperative brain fluorodeoxyglucose positron emission tomography (FDG-PET) and were followed-up for more than 1 year after CI were included. The mean age of these patients was 64.6 years (range, 60-80 years). Based on their sentence score at 1 year after CI surgery, the patients were classified into two groups: poor performers (CID score of <80) and good performers (CID score of ≥80). The duration of deafness, age at operation, preoperative residual hearing, and preoperative brain metabolism were analyzed. SPM5 software was used for FDG-PET image preprocessing and statistical analysis. Neither deafness duration nor preoperative residual hearing was associated with speech performance. The age at operation had little association with speech performance. Deaf patients whose brain metabolism was higher in frontotemporal regions became good CI users but those with higher metabolism in visual association areas became poor CI users. No significant cortical area of higher metabolism was associated with the duration of deafness. Overactivation in the visual processing pathway correlated with a poor CI outcome at 1 year. Deaf patients who are going to be poorer performers with CI devices maintain visual information processing during preoperative silent resting periods.