Regional Cerebral Metabolic Rate For Glucose Research Articles

Non-invasive assessment of stimulation-specific changes in cerebral glucose metabolism with functional PET

PurposeFunctional positron emission tomography (fPET) with [18F]FDG allows quantification of stimulation-induced changes in glucose metabolism independent of neurovascular coupling. However, the gold standard for quantification requires invasive arterial blood sampling, limiting its widespread use. Here, we introduce a novel fPET method without the need for an input function.MethodsWe validated the approach using two datasets (DS). For DS1, 52 volunteers (23.2 ± 3.3 years, 24 females) performed Tetris® during a [18F]FDG fPET scan (bolus + constant infusion). For DS2, 18 participants (24.2 ± 4.3 years, 8 females) performed an eyes-open/finger tapping task (constant infusion). Task-specific changes in metabolism were assessed with the general linear model (GLM) and cerebral metabolic rate of glucose (CMRGlu) was quantified with the Patlak plot as reference. We then estimated simplified outcome parameters, including GLM beta values and percent signal change (%SC), and compared them, region and whole-brain-wise.ResultsWe observed higher agreement with the reference for DS1 than DS2. Both DS resulted in strong correlations between regional task-specific beta estimates and CMRGlu (r = 0.763…0.912). %SC of beta values exhibited strong agreement with %SC of CMRGlu (r = 0.909…0.999). Average activation maps showed a high spatial similarity between CMRGlu and beta estimates (Dice = 0.870…0.979) as well as %SC (Dice = 0.932…0.997), respectively.ConclusionThe non-invasive method reliably estimates task-specific changes in glucose metabolism without blood sampling. This streamlines fPET, albeit with the trade-off of being unable to quantify baseline metabolism. The simplification enhances its applicability in research and clinical settings.

Cerebral Glucose Metabolism in Patients with Chronic Disorders of Consciousness.

To measure regional cerebral metabolic rate of glucose (CMRGlu) in patients with chronic disorders of consciousness (DOCs) using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective cohort study examined 50 patients (mean age: 40.9 ± 20.1 years) with traumatic brain injury (TBI)-induced chronic DOCs [minimally conscious state (MCS)+, n = 20; MCS-, n = 15 and vegetative state (VS), n = 15]. We measured FDG-PET-based CMRGlu values in 12 regions of both brain hemispheres and compared those among MCS+, MCS - and VS patients. In both hemispheres, the regional CMRGlu reduced with consciousness deterioration in 11 of 12 regions (91.7%). In seven right hemisphere regions, CMRGlu values were markedly higher in MCS+ patients than in MCS- patients. Furthermore, CMRGlu was suggestively higher in the left occipital region in MCS- patients than in VS patients. Functional preservation in the left occipital region in patients with chronic DOCs might reflect an awareness of external environments, whereas extensive functional preservation in the right cerebral hemisphere might reflect communication motivation.

Promise of Fully Integrated PET/MRI: Noninvasive Clinical Quantification of Cerebral Glucose Metabolism.

We describe a fully automated processing pipeline to support the noninvasive absolute quantification of the cerebral metabolic rate for glucose (CMRGlc) in a clinical setting. This pipeline takes advantage of “anatometabolic” information associated with fully integrated PET/MRI. Methods: Ten healthy volunteers (5 men and /5 women; 27 ± 7 y old; 70 ± 10 kg) underwent a test-retest 18F-FDG PET/MRI examination of the brain. The imaging protocol consisted of a 60-min PET list-mode acquisition with parallel MRI acquisitions, including 3-dimensional time-of-flight MR angiography, MRI navigators, and a T1-weighted MRI scan. State-of-the-art MRI-based attenuation correction was derived from T1-weighted MRI (pseudo-CT [pCT]). For validation purposes, a low-dose CT scan was also performed. Arterial blood samples were collected as the reference standard (arterial input function [AIF]). The developed pipeline allows the derivation of an image-derived input function (IDIF), which is subsequently used to create CMRGlc maps by means of a Patlak analysis. The pipeline also includes motion correction using the MRI navigator sequence as well as a novel partial-volume correction that accounts for background heterogeneity. Finally, CMRGlc maps are used to generate a normative database to facilitate the detection of metabolic abnormalities in future patient scans. To assess the performance of the developed pipeline, IDIFs extracted by both CT-based attenuation correction (CT-IDIF) and MRI-based attenuation correction (pCT-IDIF) were compared with the reference standard (AIF) using the absolute percentage difference between the areas under the curves as well as the absolute percentage difference in regional CMRGlc values. Results: The absolute percentage differences between the areas under the curves for CT-IDIF and pCT-IDIF were determined to be 1.4% ± 1.0% and 3.4% ± 2.6%, respectively. The absolute percentage difference in regional CMRGlc values based on CT-IDIF and pCT-IDIF differed by less than 6% from the reference values obtained from the AIF. Conclusion: By taking advantage of the capabilities of fully integrated PET/MRI, we developed a fully automated computational pipeline that allows the noninvasive determination of regional CMRGlc values in a clinical setting. This methodology might facilitate the proliferation of fully quantitative imaging into the clinical arena and, as a result, might contribute to improved diagnostic efficacy.

Plasma Neurofilament Light Chain Levels Are Associated With Cortical Hypometabolism in Alzheimer Disease Signature Regions.

Neurofilament light chain (NFL) has been recently introduced as a biomarker of early dementia. 18-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is a proxy for regional hypometabolism in Alzheimer disease (AD). Globally normalized 18F-FDG-PET values and levels of NFL and tau were obtained from 149 patients with mild cognitive impairment (MCI) from the baseline cohort of the Alzheimer's Disease Neuroimaging Initiative database. We adopted a stepwise partial correlation model using plasma NFL, plasma tau, CSF NFL, and regional cerebral metabolic rate of glucose (CMRGlc) as main variables, and age, sex, and Alzheimer's Disease Rating Scale (ADAS) as covariates. Significant regions were entered into a stepwise multiple regression analysis to investigate the independent correlation of each biomarker to baseline regional CMRGlc and its progression in patients with MCI. Higher baseline CSF NFL levels correlated with hypometabolism in bilateral precuneal and posterior cingulate cortex. After correction for age, sex, and ADAS score, plasma NFL levels correlated with hypometabolism in bilateral parahippocampal and middle temporal gyri. Cortical hypometabolism in bilateral parahippocampal gyri and right fusiform and middle temporal gyri was independently predicted by higher baseline plasma NFL levels in a multiple regression model. Plasma NFL promises to be an early biomarker of cortical hypometabolism in MCI and for MCI progression to AD.

Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

Association of Cerebral Metabolic Activity Changes with Vagus Nerve Stimulation Antidepressant Response in Treatment-Resistant Depression

BackgroundVagus nerve stimulation (VNS) has antidepressant effects in treatment resistant major depression (TRMD); these effects are poorly understood. This trial examines associations of subacute (3 months) and chronic (12 months) VNS with cerebral metabolism in TRMD. Objective17Fluorodeoxyglucose positron emission tomography was used to examine associations between 12-month antidepressant VNS response and cerebral metabolic rate for glucose (CMRGlu) changes at 3 and 12 months. MethodsThirteen TRMD patients received 12 months of VNS. Depression assessments (Hamilton Depression Rating Scale [HDRS]) and PET scans were obtained at baseline (pre-VNS) and 3/12 months. CMRGlu was assessed in eight a priori selected brain regions (bilateral anterior insular [AIC], orbitofrontal [OFC], dorsolateral prefrontal [DLPFC], and anterior cingulate cortices [ACC]). Regional CMRGlu changes over time were studied in VNS responders (decreased 12 month HDRS by ≥50%) and nonresponders. ResultsA significant trend (decreased 3 month CMRGlu) in the right DLPFC was observed over time in VNS responders (n = 9; P = 0.006). An exploratory whole brain analysis (Puncorrected = 0.005) demonstrated decreased 3 month right rostral cingulate and DLPFC CMRGlu, and increased 12 month left ventral tegmental CMRGlu in responders. Conclusions/LimitationsVNS response may involve gradual (months in duration) brain adaptations. Early on, this process may involve decreased right-sided DLPFC/cingulate cortical activity; longer term effects (12 months) may lead to brainstem dopaminergic activation. Study limitations included: a) a small VNS nonresponders sample (N = 4), which limited conclusions about nonresponder CMRGlu changes; b) no control group; and, c) patients maintained their psychotropic medications.

A FDG-PET and fMRI Study on Glucose Metabolism and Hemodynamic Response during Visual Attentional Performance in Schizophrenia

This research investigated the correlation between regional cerebral glucose metabolism rate (rGMR) of [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and hemodynamic response of blood-oxygen-leveldependent (BOLD) fMRI in schizophrenia during visual attentional performance. PET, MRI and fMRI images of 17 unmedicated schizophrenia patients and 38 healthy controls were acquired. A visual attention task was administered during the FDG uptake period and during the fMRI scan. Statistical parametric mapping (SPM) analysis was performed on the PET and fMRI images. Hemodynamic response curves were extracted from the frontal and temporal cortices, Anterior Cingulate Cortex (ACC), caudate and thalamus. The Area under the Curve (AUC) was calculated for each region and correlated with rGMR obtained from PET images. The results indicated that (1) Although the spatial patterns of rGMR and hemodynamic response SPMs are different, the rGMR and hemodynamic responses were significantly correlated in the frontal and temporal cortex, anterior cingulate cortex, caudate and thalamus for all subjects; (2) The patterns of the correlations are different between schizophrenia patients and controls. These results confirm the findings of our previous PET and fMRI study during auditory attentional performance, suggesting that altered blood flowmetabolic processes during neuronal activities may underlie the attention deficits in schizophrenia, which may be useful for the early diagnosis of schizophrenia.

Factor structure of regional cerebral blood flow and glucose metabolism rate as a tool to study the default mode of the brain

The functional connectivity of anatomical and functional brain structures in the state of operational rest was assessed on the basis of positron emission tomography (PET) data to study the so-called default mode of the brain, i.e., the brain’s spontaneous activity at rest. It is concluded that the possibility of identifying neuroanatomical systems of the default mode (default mode network) in routine clinical PET studies of the cerebral blood flow and glucose metabolism is important for studying the functional organization of the brain in the normal state and its rearrangements in pathologies.

Pretreatment cerebral metabolic activity correlates with antidepressant efficacy of vagus nerve stimulation in treatment-resistant major depression: A potential marker for response?

Pretreatment brain activity in major depressive disorder correlates with response to antidepressant therapies, including pharmacotherapies and transcranial magnetic stimulation. The purpose of this trial was to examine whether pretreatment regional metabolic activity in selected regions of interest (ROIs) predicts antidepressant response following 12 months of vagus nerve stimulation (VNS) in 15 patients with treatment-resistant major depression (TRMD). Fluorodeoxyglucose positron emission tomography (FDG PET) was used to assess regional mean relative cerebral metabolic rate for glucose (CMRGlu) in four ROIs (anterior insular, orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices) at baseline (prior to VNS activation). Depression severity was assessed at baseline and after 12 months of VNS using the Hamilton Depression Rating Scale (HDRS), with response defined as ≥ 50% reduction in HDRS from baseline. Baseline CMRGlu in the anterior insular cortex differentiated VNS responders (n=11) from nonresponders (n=4) and correlated with HDRS change (r=.64, p=.01). In a regression analysis, lower anterior insular cortex CMRGlu (p=.004) and higher orbitofrontal cortex CMRGlu (p=.047) together predicted HDRS change (R(2)=.58, p=.005). In a whole brain, voxel-wise analysis, baseline CMRGlu in the right anterior insular cortex correlated with HDRS change (r=.78, p=.001). Sample size was small, limiting statistical power; patients remained on their psychiatric medications; study was open-label and uncontrolled. This preliminary study suggests that pretreatment regional CMRGlu may be useful in predicting response to VNS in TRMD patients.

Dynamic FDG PET for assessing early effects of cerebral hypoxia and resuscitation in new-born pigs

Changes in cerebral glucose metabolism may be an early prognostic indicator of perinatal hypoxic-ischaemic injury. In this study dynamic ¹⁸F-FDG PET was used to evaluate cerebral glucose metabolism in piglets after global perinatal hypoxia and the impact of the resuscitation strategy using room air or hyperoxia. New-born piglets (n = 16) underwent 60 min of global hypoxia followed by 30 min of resuscitation with a fraction of inspired oxygen (FiO₂) of 0.21 or 1.0. Dynamic FDG PET, using a microPET system, was performed at baseline and repeated at the end of resuscitation under stabilized haemodynamic conditions. MRI at 3 T was performed for anatomic correlation. Global and regional cerebral metabolic rates of glucose (CMRgl) were assessed by Patlak analysis for the two time-points and resuscitation groups. Global hypoxia was found to cause an immediate decrease in cerebral glucose metabolism from a baseline level (mean ± SD) of 21.2 ± 7.9 to 12.6 ± 4.7 μmol/min/ 100 g (p <0.01). The basal ganglia, cerebellum and cortex showed the greatest decrease in CMRgl but no significant differences in global or regional CMRgl between the resuscitation groups were found. Dynamic FDG PET detected decreased cerebral glucose metabolism early after perinatal hypoxia in piglets. The decrease in CMRgl may indicate early changes of mild cerebral hypoxia-ischaemia. No significant effect of hyperoxic resuscitation on the degree of hypometabolism was found in this early phase after hypoxia. Cerebral FDG PET can provide new insights into mechanisms of perinatal hypoxic- ischaemic injury where early detection plays an important role in instituting therapy.

Regional cerebral blood flow and glucose metabolism during propofol anaesthesia in healthy subjects studied with positron emission tomography

General anaesthetics can alter the relationship between regional cerebral glucose metabolism rate (rGMR) and regional cerebral blood flow (rCBF). With the present study, we wanted to assess quantitatively the effects of propofol on rCBF and rGMR in the same healthy volunteers measured with positron emission tomography (PET). (15)O-labelled water and (18)F fluorodeoxyglucose were used as PET tracers to determine rCBF and rGMR, respectively, in eight healthy volunteers during the waking state (baseline) and during propofol anaesthesia. Propofol was titrated to keep a constant hypnotic depth (Bispectral Indes 35-40) throughout the anaesthesia. Changes in rGMR and rCBF were quantified using region-of-interest and voxel-based analyses. The measured mean propofol concentration was 4.1 ± 0.8 μg/ml during anaesthesia. Compared with the conscious state, total CBF and GMR decreased during the anaesthetic state with 47% and 54%, respectively. In the white and grey matter, rCBF and rGMR were reduced by 37% and 49%, and by 45% and 57%, respectively. Propofol decreased rCBF in all brain structures by 46-55% (P ≤ 0.01) with highest significant decreases in the thalamus and parietal lobe. Regional GMR was reduced in all brain areas to 48-66% (P ≤ 0.01) with highest significant reductions in the occipital lobe, the lingual gyrus, parietal lobe, temporal lobe and thalamus. No increases in rCBF or rGMR happened anywhere. General anaesthesia with propofol is associated with a global metabolic and vascular depression in the human brain, with significant shifts in regional blood flow and metabolism indicating marked metabolic and vascular responsiveness in some cortical areas and thalamus.

Donepezil causes acute increases in regional cerebral blood flow in normal rat

associated to aging and AD. (Kalpouzos 2009, Mosconi, 2007). We focused on the small primate (Microcebus murinus (M.m.), during aging some animals develop cognitive impairments (Picq, 2007), amyloid plaque depositions, and altered Tau protein accumulation associated with cerebral atrophy (Kraska, 2009). Brain atrophy is predictive of cognitive alterations (Picq, 2010). The aim of the current study was to evaluate age-associated evolution of glucose uptake in M.m. by using non-invasive FDG PET. Methods: SeventeenM.m. (1.5 to 9 years) were evaluated by PET with MicroPET Focus220 system (FDG: 900mCurie/100g, i.v.) and 3D-MR images were recorded (PharmaScan Bruker 7T). M.m were anesthetized by isoflurane duringimages acquisition. MR and PET images were co-registered by rigid transformations to define volumes of interest (VOI) in brain and appraise Standard UptakeValues (SUV) as well as relative values as compared to whole brain. Results: MR images didn’t reveal any severe atrophy this study is focused on normal aging. PET study revealed a relationship between age and SUVs in the frontal cortex, the cerebellum, and in the whole brain. However, relative values were not correlated with age. The cohort was split by theM.m.midlife (4.5 years) in two groups, young (1.960.2 years) and old animals (6.460.5 years).This second analyse showed a difference between young and old animals in thewhole brain, frontal cortex and cerebellum (t-test).Conclusions:Anage-associated evolution of glucose uptake as measured by SUVs could bedetected in non-severely atrophied M.m. and resembles evolution of the regionalcerebral metabolic rates for glucose (rCMRGlc) observed in healthy aged humans.This study is a first step toward the characterization of age-associated changesof brain glucose uptake inM.m. and will be useful to understand brain aging inM.m.

Establishment of In Vivo Brain Imaging Method in Conscious Mice

In vivo imaging, such as PET, requires restriction of body movements and is generally conducted under sedation by anesthetic agents in studies using laboratory animals. Because anesthetics reduce neural activity and metabolism, physiologic neural functions are difficult to assess in animal PET studies. Therefore, use of an appropriate method in conscious animals is important and is a practical requirement for physiologic in vivo brain imaging studies. Here, we established an in vivo imaging system for conscious mice to reveal the physiologic regional cerebral glucose metabolic rate (rCMRglu) with (18)F-FDG PET. We first developed a head holder to enable brain PET of a conscious mouse. To obtain optimal rCMRglu, we examined the effects of physical and psychologic stresses caused by ambient temperature, intravenous injection, and acclimation to the apparatus and immobile state. Finally, quantitative kinetic analysis was performed for rCMRglu based on a 2-tissue-compartment model with an input function of arterial blood sampling under both conscious and anesthetized (1.5% isoflurane) conditions. Increasing the ambient temperature increased uptake of (18)F-FDG in the brain significantly while reducing the uptake in skeletal muscle and brown adipose tissue that was caused by shivering. The reduction of brain (18)F-FDG uptake caused by tail holding and manual injection was significantly ameliorated by the use of an automated slow injection. Although brain uptake of (18)F-FDG varied at the first session of PET, uptake at the second and subsequent sessions was stable, even after long-term acclimation. After these beneficial changes, brain uptake of (18)F-FDG improved significantly, to approximately 260% above the preconditioned state, which is comparable with that obtained in mice that have been allowed to move freely about their home cages. Quantitative kinetic analyses revealed that isoflurane anesthesia lowered rCMRglu in the cerebral cortex, striatum, thalamus, and cerebellum by 66%, 59%, 62%, and 22%, respectively, mainly by reducing the k(3) value, a rate constant for phosphorylation by hexokinase. To our knowledge, this is the first study to report quantitative kinetic analysis of rCMRglu in mice that have been conscious throughout PET. This investigation will open avenues for research into in vivo functional brain molecular imaging in both normal and genetically manipulated mice.

Amyloid and tau imaging, neuronal losses and function in mild cognitive impairment.

Establish new approaches for early diagnosis of dementia, based on imaging amyloid and tau pathology, cell losses and neuronal function, in subjects with mild cognitive impairment (MCI),. The overall aim is to develop effective tools for monitoring disease progression in the living patient to facilitate discovery of early therapeutic interventions to modify the course of the disease. Use 2-(1-{6-[(2-[F- 18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) in combination with positron emission tomography (PET) to produce dynamic images for quantification of regional cortical brain deposition in MCI patients and compare them with controls subjects and patients with Alzheimer's disease (AD). Comparison with other molecular imaging probes for neuronal losses and function were also made. Patients are positioned supine in the tomograph bed with his/her head in the detector ring field. Upon injection of the molecular imaging probe (e.g., [F-18]FDDNP) images are obtained at very short time intervals for up to two hours. This results in dynamic sequences of brain distribution of the probe. Patients with clinical diagnosis of AD, MCI and control subjects. Subjects in the categories established above were scanned with [F-18]FDDNP-PET and quantification performed using Logan parametric graphical analysis to measure relative quantitative amyloid loads throughout the brain within patient groups. These results were compared in the same patients with cell losses in hippocampus using 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)- 1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide,([F-18]MPPF) and regional cerebral glucose metabolic rates using 2-deoxy-2-[F-18]fluoro-2-deoxy-D-glucose (2-[F-18]FDG). [F-18]FDDNP reliably follows neuropathological progression (amyloid plaques [SP]; neurofibrillary tangles [NFT]) in the living brain of AD patients and those with MCI. The distribution of [F-18]FDDNP brain cortical accumulation correlates well with behavioral measures (e.g., MMSE scores) and follows known patterns of pathological distribution observed at autopsy. We have also established conversion of controls to MCI and MCI to AD with precision and sensitivity in patients and control subjects in follow-up studies. Moreover, we have established that hemispheric cortical surface mapping of [F-18]FDDNP binding is a powerful tool for assessment and visualization of the rate of brain pathology deposition. A strong correlation of [F-18]FDDNP binding, cell losses in hippocampus and decreased glucose utilization ([F-18]FDG PET) in several neocortical regions was found in the same AD and MCI subjects. The combined evaluation of [F-18]FDDNP PET (targeting NFT and_SP) with neuronal losses in the hippocampus and with [F-18]FDG PET (targeting neuronal function) offers the opportunity for reliable, noninvasive detection of MCI patients at risk for AD. The approach offers a glimpse to the molecular and cellular mechanisms associated with dementia and provides a means for their assessment in the living patient. Monitoring disease progression in MCI patients demonstrates the usefulness of this imaging approach for early diagnosis and provides a means for evaluation of neuroprotective agents and drugs aimed at prevention and modification of disease progression.

P2-180: Regional cerebral metabolic differences of mild cognitive impairment (MCI) by delayed recall impairment degree

Mild cognitive impairment (MCI) is one of the widely used concepts indicative of the transitional cognitive condition between normal aging and dementia. However, there have been no standardized indices defining memory impairment of MCI. This study was to elucidate the cerebral metabolic differences between MCI groups divided by the degree of delayed recall impairment. All candidates were examined by neuropsychiatrists according to the protocol of the Korean Version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD–K). They also underwent [18F] fluoro–deoxyglucose positron emission tomography (18F–FDG PET) scan. 63 right–handed MCI (Total MCI; T–MCI) patients were recruited by diagnostic criteria, which were cognitive impairment necessarily including memory impairment; essentially preserved general cognitive function; largely intact functional activities; not demented. Among them 55 MCI patients over 60 years were divided into two subgroups according to the presence of impairment in any of two delayed recall measures in the CERAD–K neuropsychological battery: 20 MCI patients with impaired delayed recall (DR+MCI); and 35 MCI patients with intact delayed recall (DR–MCI). Delayed recall impairment is performance of 1.5 or more SDs below the age, sex, and education norm on CERAD Word list recall or Constructional recall test. 25 healthy control subjects (NC) were recruited. The differences in the regional cerebral glucose metabolic rate between each MCI and NC group were tested on a voxel–by–voxel basis using the Statistical Parametric Mapping (SPM) 99 software (p < 0.05, corrected). Compared to the NC subjects, the bilateral posterior cingulate cortex (PCC) and right splenium of cingulum in T–MCI patients showed hypometabolism. DR+MCI patients showed hypometabolism in the bilateral PCC and right splenium of cigulum, while the right splenium of cingulum in DR–MCI patients showed decreased metabolism compared to NC. Additionally, compared to DR–MCI patients, DR+MCI patients showed a hypometabolic trend in right parahippocampal gyrus (p < 0.001, uncorrected). These investigations generally have emphasized that brain functional differences were found according to the degree of delayed recall impairment in MCI which may prove useful for clinicians in early detection and determining the diagnostic index of MCI.

Visual hallucination in Parkinson's disease with FDG PET.

To determine the characteristics of cerebral glucose metabolism in Parkinson's disease patients with visual hallucinations, group comparison studies using [18F]fluorodeoxyglucose positron emission tomography were performed. Nondemented Parkinson's disease patients in advanced stages were classified into two groups: (1) patients without visual hallucinations; (2) patients with visual hallucinations. Compared to patients without hallucinations, the relative regional cerebral glucose metabolic rate was greater in the frontal areas in patients with visual hallucinations, and the increase reached a significant level in the left superior frontal gyrus. Relative frontal hypermetabolism may be a feature of Parkinson's disease patients with visual hallucinations.

A 90-year-old monozygotic female twin pair discordant for Alzheimer’s disease

The present study describes PET, MRI, and neuropsychological findings in 90-year-old monozygotic female twins, who have remained discordant for probable Alzheimer’s disease (AD) for at least 7 years. These findings were compared with those of healthy persons composing the reference group (seven women, three men; the mean±S.D. age: 73.3±3.3 years). Twins’ life histories were remarkably similar, except for continuous NSAID use of the unaffected twin for decades. The regional cerebral glucose metabolic rates (rCMRgluc) and all but two CERAD test scores of the affected twin were more than 2 S.D. below the mean values of the reference group. These values were normal in the unaffected twin. The affected twin had moderate hippocampal and temporoparietal atrophy, whereas the hippocampi were intact, and cortical atrophy was mild in the unaffected twin. These findings indicate that the twins were discordant for AD, even though they had reached the age in which the prevalence of AD is high among women. Our results further address the influence of environmental factors on the onset of AD, especially the possible protective effect of anti-inflammatory medication.

Left prefrontal-repetitive transcranial magnetic stimulation (rTMS) and regional cerebral glucose metabolism in normal volunteers

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a probe into the pathophysiology and possible treatment of neuropsychiatric disorders. To explore its regional effects, we combined rTMS with positron emission tomography (PET). Fourteen healthy volunteers participated in a baseline 18-fluorodeoxyglucose (FDG) PET scan. During a second FDG infusion on the same day, seven subjects received 30 min of 1 Hz rTMS at 80% of motor threshold to left prefrontal cortex, and seven other subjects received sham rTMS under identical conditions. Global and normalized regional cerebral glucose metabolic rates (rCMRglu) from the active and sham conditions were compared to baseline and then to each other. Sham, but not active 1 Hz rTMS, was associated with significantly increased global CMRglu. Compared to baseline, active rTMS induced normalized decreases in rCMRglu in right prefrontal cortex, bilateral anterior cingulate, basal ganglia (L>R), hypothalamus, midbrain, and cerebellum. Increases in rCMRglu were seen in bilateral posterior temporal and occipital cortices. Sham rTMS compared to baseline resulted in isolated normalized decreases in rCMRglu in left dorsal anterior cingulate and left basal ganglia, and increases in posterior association and occiptal regions. Differences between the 1 Hz active versus sham changes from baseline revealed that active rTMS induced relative decrements in rCMRglu in the left superior frontal gyrus and increases in the cuneus (L>R). One Hertz rTMS at 80% motor threshold over the left prefrontal cortex in healthy subjects compared to sham rTMS in another group (each compared to baseline) induced an area of decreased normalized left prefrontal rCMRglu not directly under the stimulation site, as well as increases in occipital cortex. While these results are in the predicted direction, further studies using other designs and higher intensities and frequencies of rTMS are indicated to better describe the local and distant changes induced by rTMS.

Hierarchical clustering of Alzheimer and "normal" brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

Brain tissue samples, obtained from the Alzheimer Disease Brain Bank,Institute of Psychiatry, London, were taken from both left and right hemispheresof three regions of the cerebrum, namely the frontal, parietal and occipitallobes for both Alzheimer and 'normal' subjects. Trace elementconcentrations in the frontal lobe were determined for twenty six Alzheimer(15 male, 11 female) and twenty six 'normal' (8 male, 18 female)brain tissue samples. In the parietal lobe ten Alzheimer (2 male, 8 female)and ten 'normal' (8 male, 2 female) samples were taken along withten Alzheimer (4 male, 6 female) and ten 'normal' (6 male, 4 female)from the occipital lobe. For the frontal lobe trace element concentrationswere determined using proton induced X-ray emission (PIXE) analysis whilein parietal and occipital regions instrumental neutron activation analysis(INAA) was used. Additionally eighteen Alzheimer (9 male, 9 female) and eighteenage matched 'normal' (8 male, 10 female) living subjects wereexamined using positron emission tomography (PET) in order to determine regionalcerebral metabolic rates of glucose (rCMRGlu). The rCMRGlu of 36 regions ofthe brain was investigated including frontal, occipital and parietal lobesas in the trace element study. Hierarchical cluster analysis was applied tothe trace element and glucose metabolism data to discover which variablesin the resulting dendrograms displayed the most significant separation betweenAlzheimer and 'normal' subjects.