Changes In Regional Cerebral Metabolism Research Articles

Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: A double-blinded placebo controlled pilot study

BackgroundNatural compounds in grapes such as resveratrol are known for their antioxidant and anti-inflammatory properties. Some studies have shown a potential role for grapes or wine in slowing cognitive decline and other effects of aging. However, well-controlled experimental data obtained in human subjects are still in need of further development. Here we aimed to systematically assess effects of grapes on regional cerebral metabolism. MethodsTen subjects with mild decline in cognition (mean, 72.2±4.7years; 50% female) were included in this analysis. Participants were randomized into an active grape formulation arm or a placebo arm which consumed a formulation free of polyphenols for six months. Cognitive performance was measured through neuropsychological assessments performed at baseline and 6months after initiation of therapy. Changes in brain metabolism occurring with each therapy regimen were assessed by brain PET scans with the radiotracer [F-18] fluorodeoxyglucose (FDG), obtained during initial evaluation and 6months later. Standardized volumes of interest (sVOI) and statistical parametric mapping (SPM) methods were applied to FDG-PET scans to identify significant regional cerebral metabolic changes. ResultsIn contrast to participants taking the active grape formulation, who displayed no significant decline in metabolism, the placebo arm underwent significant metabolic decline in sVOI's of the right posterior cingulate cortex (p=0.01), and left superior posterolateral temporal cortex (p=0.04). SPM analyses also found significant declines in the placebo group, particularly in left prefrontal, cingulate, and left superior posterolateral temporal cortex (p<0.01) with stable brain metabolism in the active formulation arm. No significant differences were seen in scores on the neuropsychological battery of tests between the two groups. However, metabolism in right superior parietal cortex and left inferior anterior temporal cortex was correlated with improvements in attention/working memory, as measured with WAIS-III Digital Span within the active formulation group (r=−0.69, p=0.04). ConclusionsThe placebo arm had declines in regions of the brain known to be significantly affected in the early stages of Alzheimer's disease, while the active formulation group was spared such decline. This suggests a protective effect of grapes against early pathologic metabolic decline.

Viability assessment of magnetic resonance spectroscopy for the detection of minimal hepatic encephalopathy severity

ObjectiveTo evaluate regional cerebral metabolic changes in minimal hepatic encephalopathy (MHE) patients using magnetic resonance spectroscopy (MRS) in 3T scanner. Materials and methodsThis study comprised 30 cirrhotic patients with MHE, 29 cirrhotic patients without MHE and 30 healthy volunteers. Single-voxel proton MRS data in the anterior cingulate cortex (ACC) and basal ganglia were acquired using a 3-T scanner. The concentrations of N-acetylaspartate (NAA), mI (myo-inositol), glutamate (Glu), glutamine (Gln) and creatine (Cr) were obtained by LC-model software. Statistical analysis was performed to evaluate the differences between the three groups. ResultsThere was a significant increase in Glu for the cirrhotic patients, particularly the MHE patients. There was an elevation of Gln in the cirrhotic patients, but not in all cirrhotic patients or controls. There was a significant decrease in mI for the cirrhotic patients, but no significant difference between the two cirrhosis groups. There was no significant difference in NAA between the three groups. ConclusionsMRS using a 3-T MR scanner could detect cerebral metabolic changes in cirrhotic patients with MHE. Glu levels were elevated in cirrhotic patients with MHE; Glu levels could be used as a sensitive indicator to evaluate the severity of MHE in patients with cirrhosis.

Card-placing test in amnestic mild cognitive impairment and its neural correlates.

BackgroudWe investigated anatomical correlates of the card-placing test (CPT) in patients with amnestic mild cognitive impairment (aMCI).MethodsFifteen aMCI patients underwent part A and part B of the CPT and FDG-PET. The CPT scores and MMSE scores of 29 cognitively normal people were used for comparison. Statistical parametric mapping (SPM) correlation analysis was used to extract the regions whose changes in regional cerebral metabolism correlated significantly with part A and B of the CPT with adjustment of age, education and sex of patients.ResultsThe aMCI patients had significantly lower MMSE scores (26.0 ± 2.0 vs. 28.2 ± 1.4, p < 0.001), CPT A (25.5 ± 3.5 vs. 27.7 ± 2.7, p = 0.026) and CPT B scores (16.3 ± 4.4 vs. 19.7 ± 3.7, p = 0.011) compared to the normal population. The test scores of part B of the CPT correlated well with hypometabolism of the posterior cingulate gyrus and precuneus.ConclusionsThis study suggests that the CPT B may reflect the functional status of the posterior cingulate gyrus in patients with aMCI.

The Effect of Aromatase Inhibition on the Cognitive Function of Older Patients With Breast Cancer

IntroductionThis study evaluated the association between aromatase inhibitor (AI) therapy and cognitive function (over a 6-month period) in a cohort of patients aged ≥ 60 years compared with an age-matched healthy control group, and it evaluated changes in regional cerebral metabolism as measured by positron emission tomography (PET) scans of the brain done in a subset of the patient cohort. Patients and MethodsThirty-five patients (32 evaluable) and 35 healthy controls were recruited to this study. Patients with breast cancer completed a neuropsychological battery, self-reported memory questionnaire, and geriatric assessment before initiation of AI therapy and again 6 months later. Age-matched healthy control participants completed the same assessments at the same time points as the patient group. ResultsNo significant decline in cognitive function was seen among individuals receiving an AI from pretreatment to 6 months later compared with healthy controls. In the PET cohort over the same period, both standardized volume of interest and statistical parametric mapping analyses detected specific changes in metabolic activity between baseline and follow-up uniquely in the AI patients, most significantly in the medial temporal lobes. ConclusionAlthough patients undergoing AI treatment had few changes in neuropsychological performance compared with healthy controls over a 6-month period, regionally specific changes in cerebral metabolic activity were identified during this interval in the patient group. Additional longitudinal follow-up is needed to understand the potential clinical implications of these findings.

Stability in Brain Glucose Metabolism Following Brown Adipose Tissue Inactivation in Chinese Adults

The thermogenesis of BAT is believed to be controlled through some pathways initiated in the brain, though the changes in brain activity among different states of BAT-positive subjects are still unclear. We hypothesized that some significant differences of regional cerebral metabolism between various groups were related to the BAT activities regardless of temperature changes. Relative regional cerebral glucose metabolism was compared between 15 healthy subjects with activated BAT and 30 healthy controls without activated BAT by using a brain FDG-PET scan. A follow-up PET scan was performed to assess metabolic changes of the brain when BAT activity was eliminated by heat exposure. Compared with controls, BAT-positive subjects exhibited lower activity in the inferior parietal lobule, limbic system, and frontal lobe and higher activity in the precuneus before heat exposure. Compared with the BAT elimination status, subjects with activated BAT showed a decreased metabolism in the parietal lobe, frontal lobe, culmen, cingulate gyrus, and sublobar region. Compared with controls, BAT-positive subjects after BAT inactivation had significant hypometabolic areas in the temporal lobe and limbic lobe and hypermetabolic areas in the parietal lobe. Our findings illustrate that changes of regional cerebral metabolism are related to BAT activities regardless of temperature changes. This before-after controlled study supports the finding that the brain responses appear to be active in modulating the metabolic function of BAT activity.

Mild Traumatic Brain Injury from Primary Blast vs. Blunt Forces: Post-Concussion Consequences and Functional Neuroimaging (P01.178)

Objective: This study investigated changes in functional health and well-being, cognition, and functional neuroimaging among Iraq/Afghanistan veterans who sustained pure blast-force mild traumatic brain injury (mTBI), as compared to those who sustained pure blunt-force mTBI. The aim was to document post-concussion consequences and associated changes in cerebral metabolism from mTBI due to blast forces. Background Injuries from blast forces are a hallmark of the conflicts in Iraq and Afghanistan and may cause undetected neurological dysfunction from mTBI. The effects of primary blast overpressure on the brain have been difficult to clarify because of complications, such as secondary and tertiary blast effects and comorbid post-traumatic stress disorder (PTSD). Design/Methods: Inclusion criteria included presence of pure blast or blunt injury, absence of PTSD, and between 6-36 months post-trauma. The Blast Group (n=12) and the Blunt Group (n=12) underwent assessments of well-being, cognition, and resting fluorodeoxyglucose positron emission tomography (PET). Results: There were no group differences on mTBI-related variables, the Rivermead Post-Concussion Questionnaire (RPQ), or the SF36-V Health Survey. Both groups, however, did worse than published norms on the RPQ and SF36-V, and the Blast Group had additional worse SF36-V subscale scores on Bodily Pain and Social Functioning. Compared to the Blunt Group, the Blast Group had poorer scores on the Paced Auditory Serial Addition Test (PASAT) and greater PET hypometabolism in the right superior parietal region. Only the Blast Group had significant correlations of their RPQ, SF36-V Mental Composite Score, and PASAT scores with specific regional metabolic changes. Conclusions: Together these results suggest that pure blast force mTBI has post-concussion consequences. Blast mTBI may cause deficits in well-being, possibly from an altered bodily self-image, and in attentional control. These changes are associated with regional changes in cerebral metabolism, particularly hypometabolism in the right hemisphere. Supported by: Department of Veteran9s Affairs Grant. Disclosure: Dr. Mendez has nothing to disclose. Dr. Licht has nothing to disclose. Dr. Berenji has nothing to disclose. Dr. Peppers has nothing to disclose.

Reversible Changes in Brain Glucose Metabolism Following Thyroid Function Normalization in Hyperthyroidism

Patients with hyperthyroidism frequently present with regional cerebral metabolic changes, but the consequences of endocrine-induced brain changes after thyroid function normalization are unclear. We hypothesized that the changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroid, and some of these changes can be reversed with antithyroid therapy. Relative regional cerebral glucose metabolism was compared between 10 new-onset untreated patients with hyperthyroidism and 20 healthy control participants by using brain FDG-PET scans. Levels of emotional distress were evaluated by using the SAS and SDS. Patients were treated with methimazole. A follow-up PET scan was performed to assess metabolic changes of the brain when thyroid functions normalized. Compared with controls, patients exhibited lower activity in the limbic system, frontal lobes, and temporal lobes before antithyroid treatment. There were positive correlations between scores of depression and regional metabolism in the cingulate and paracentral lobule. The severity of depression and anxiety covaried negatively with pretreatment activity in the inferior temporal and inferior parietal gyri respectively. Compared with the hyperthyroid status, patients with normalized thyroid functions showed an increased metabolism in the left parahippocampal, fusiform, and right superior frontal gyri. The decrease in both FT3 and FT4 was associated with increased activity in the left parahippocampal and right superior frontal gyri. The changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroidism, and some cerebral hypometabolism can be improved after antithyroid therapy.

Magnetic resonance spectroscopic study on regional cerebral metabolic changes of rabbits with explosive brain injury

Objective To evaluate the regional cerebral metabolic changes in different episodes by magnetic resonance spectroscopy (MRS) after explosive brain injury in rabbits. Methods Fortyfive New Zealand white rabbits were randomly divided into eight groups, ie, normal control group( 10 rabbits) and trauma group (35 rabbits). The explosive injury in trauma group was induced by explosion of 600 mg TNT equivalent of paper detonators at 6.5 cm above the rabbit brain. The rabbits in trauma group was divided into 1,6, 12, 24 hours, 3, 7, 14 days subgroups (6 rabbits per group). The survival rate was observed at different time points after explosive injury. The MRS was used to detect the regional cerebral metabolic changes including N-acetylaspartate (NAA)/creatine (Cr) ratio and choline(Cho)/Cr ratio as well as evolution of blast injuries over time. Results The rabbits survived for overseven days in the trauma groups, with typical brain contusion manifested by pathological and conventional MRI. Compared with the normal control group, the NAA/Cr ratio was markedly decreased at one hour after injury, slightly rose again at 24 hours and fell again after seven days. The Cho/Cr ratio was markedly increased at one hour after injury, slightly fell again at 12 hours and rose again at three days after injury.Conclusions MRS can manifest the regional cerebral metabolic changes of rabbits with explosive injury at different time points and hence provide a theoretical basis for understanding the local tissue changes and determining the type of tissue damage after blast injury. Key words: Brain injuries; Blast injuries; Spectroscopy

Comparing Fludeoxyglucose F18–PET Assessment of Regional Cerebral Glucose Metabolism and [11C]Dihydrotetrabenazine–PET in Evaluation of Early Dementia and Mild Cognitive Impairment

To compare assessment of regional cerebral metabolic changes with [(11)C]dihydrotetrabenazine (DTBZ)-positron emission tomography (PET) measurement of regional cerebral blood flow (K(1)) and fludeoxyglucose F18 (FDG)-PET measurement of regional cerebral glucose uptake (CMR(glc)) in a clinically representative sample of subjects with mild dementia and mild cognitive impairment (MCI). [(11)C]Dihydrotetrabenazine-PET K(1) and FDG-PET CMR(glc) measurements were performed. University-based cognitive disorders clinic. Fifty subjects with either mild dementia (Mini-Mental State Examination score > or = 18) or MCI. Their results were compared with those of 80 normal control subjects. The DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were compared with standard correlation analysis. The overall patterns of DTBZ-PET K(1) and FDG-PET CMR(glc) deficits were assessed with stereotaxic surface projections (SSPs) of parametric images. The DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were highly correlated, both within and between subjects. The SSP maps of deficits in DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were markedly similar. The DTBZ-PET K(1) SSP maps exhibited a mild decrease in sensitivity relative to FDG-PET CMR(glc) maps. Both DTBZ-PET K(1) and FDG-PET CMR(glc) measurements provide comparable information in assessment of regional cerebral metabolic deficits in mild dementia and MCI. Blood flow measures can assess regional cerebral metabolism deficits accurately in mild dementia and MCI. Blood flow assessments of regional cerebral metabolic deficits can be combined with tracer binding results to improve utility of PET imaging in mild dementia and MCI.

Heterogeneous regional and temporal energetic impairment following controlled cortical impact injury in rats

Objectives: Following traumatic brain injury metabolic stability is impaired. Duration and reversibility of these changes might be important to guide specific interventions.Methods: To characterize temporal and regional changes in cerebral metabolism, 68 male Sprague–Dawley rats were subjected to a focal cortical contusion. Lesion progression and mitochondrial impairment were determined by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride (TTC) staining, respectively. Metabolic alterations were determined at hours 6 and 24 and day 7 by measuring extracellular glucose, lactate and hypoxanthine levels with microdialysis catheters placed adjacent and distant to the contusion and by quantifying changes in tissue ATP, lactate and glucose using bioluminescence imaging.Results: The cortical lesion reached its maximal extent at hour 24 and remained confined to the ipsilateral hemisphere. In microdialysate, at hour 6, extracellular hypoxanthine and lactate reached maximal values, thereafter hypoxanthine normalized while lactate remained increased. Extracellular glucose reached the highest values at hour 24 and remained elevated. Bioluminescence imaging revealed heterogeneous changes in areas distant to the contusion. No significant changes were found in ATP content. Slightly elevated tissue glucose until 24 hours in the ipsilateral hemisphere was observed. Following a continuous increase, lactate levels were the highest by 6 hours in the ipsilateral cortex and hippocampus.Discussion: CCI is associated with disturbances in energetic metabolism. Metabolic perturbation is not restricted to the early phase and the contusional region following focal cortical contusion, but also involves hippocampus and primarily uninjured parts of the hemisphere.

Age- and transgene-related changes in regional cerebral metabolism in PSAPP mice

In parallel to imaging studies in humans with Alzheimer's disease (AD), we have mapped brain metabolic activity in transgenic mouse models of AD. Our aim in both is to provide new surrogate markers of progression to help clarify disease mechanisms and rapidly screen candidate therapeutics. Since previous findings of preferential reductions in posterior cingulate glucose metabolism may have been confounded by morphological abnormalities in previously studied “PDAPP” transgenic mice, we first assessed hippocampal and callosal anatomy in PSAPP (PS1×APP) mice, another transgenic mouse model of AD, and found no major abnormalities. We then used fluorodeoxyglucose (FDG) autoradiography in older and younger PSAPP and wildtype mice to assess the functional state of 56 regions-of-interest across group, age and increasing amyloid load. Reductions in FDG uptake in aged transgenic mice, with significant interactions between group and age, were found in retrosplenial cingulate gyrus, found to be metabolically affected in persons affected by or at risk for AD, and in brain regions known to participate with retrosplenial cingulate in networks contributing to spatial learning deficits found in these animals. Like patients with AD, PSAPP mice have age-related metabolic reductions in posterior cingulate cortex, a finding that does not appear to be related to morphological abnormalities. If longitudinal studies support these progressive and preferential reductions in retrosplenial metabolism in PSAPP mice, these reductions could provide an indicator of disease progression, help bridge the gap between human and animal studies of AD, and aid in clarification of disease mechanisms and screening of promising treatments.

P2-374: MR-guided 3D PET mapping of longitudinal changes in regional cerebral metabolism of normal subjects

P2-374: MR-guided 3D PET mapping of longitudinal changes in regional cerebral metabolism of normal subjects

IC-P-085: MR-guided 3D PET mapping of longitudinal changes in regional cerebral metabolism of normal subjects

IC-P-085: MR-guided 3D PET mapping of longitudinal changes in regional cerebral metabolism of normal subjects

Subarachnoid hemorrhage induces dynamic changes in regional cerebral metabolism in rats.

Following a subarachnoid hemorrhage (SAH), adult rats exhibit dynamic regional changes in cerebral glucose metabolism characterized by an increase in metabolic rates and a subsequent upregulation of cytochrome oxidase (CO). We evaluated both local cerebral metabolic rates for glucose (ICMRglc: (mol/100 g/min) and CO in 23 brain regions of interest (ROI). Sham animals underwent anesthesia and superficial surgery; saline-controls received an injection of 0.9% saline into the cisterna magna; and SAH rats received an injection of autologous blood into the cisterna magna. This blood, measured by albumin labeled with radioactive carbon 14, distributed throughout the brain but predominated ventrally. After experimental animals were sacrificed at day 0 (3 h), 1, 3, and 7 days postinjection, ROI were analyzed using [14C]2-deoxy-D-glucose autoradiography and CO histochemistry. ICMRglc in SAH rats increased in many regions (ranging from 0.7% to 32.2% above sham levels). Cytochrome oxidase also increased from 1% to 9% above sham levels, peaking on day 3. Conversely, saline-controls exhibited prolonged depression of ICMRglc (ranging from 11% to 35% below sham levels) and CO (ranging from 4% to 11% below sham levels) from day 0 through day 7. All saline-control ROI for all time points showed this metabolic depression, and between 91% and 95% of saline-control ROI presented lower CO levels as compared to sham. Overall, ICMRglc and CO levels were greater in SAH than in saline-control ROI. However, when considering the influence of subarachnoid blood on metabolic changes in SAH animals, both CO and 2DG levels did not correlate well with the amount of 14C-albumin binding. While previous studies have measured both metabolic rates of glucose and CO soon after SAH, this is the first to simultaneously conduct these measurements in the same SAH rat model.

Changes in regional cerebral metabolism during systemic hyperthermia in humans.

Whole body hyperthermia may produce vasodialation, nausea, and altered cognitive function. Animal research has identified brain regions that have important roles in thermoregulation. However, differences in both the cognitive and sweating abilities of humans and animals implicate the need for human research. Positron emission tomography (PET) was used to identify brain regions with altered activity during systemic hyperthermia. Human subjects were studied under cool (control) conditions and during steady-state hyperthermia induced by means of a liquid-conditioned suit perfused with hot water. PET images were obtained by injecting [(18)F]fluorodeoxyglucose, waiting 20 min for brain uptake, and then scanning for 10 min. Heating was associated with a 23% increase in resting metabolic rate. Significant increases in cerebral metabolic rate occurred in the hypothalamus, thalamus, corpus callosum, cingulate gyrus, and cerebellum. In contrast, significant decreases occurred in the caudate, putamen, insula, and posterior cingulum. These results are important for understanding the mechanisms responsible for altered cognitive and systemic responses during hyperthermia. Novel regions (e.g., lateral cerebellum) with possible thermoregulatory roles were identified.

Effects of amphetamine challenge on local cerebral glucose utilization after chronic dopamine D 1 and D 2 receptor agonist administration to rats

Repeated amphetamine administration can cause an augmentation of regional cerebral metabolic activity. This study analyzed the regional cerebral metabolic changes which occurred in rats after pretreatment with the selective dopamine D 1 and D 2 receptor agonists, (±)SKF 38393 ((±)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine HCl) and quinpirole ( trans-(−)-4a R-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3,4-g)quinoline), as measured by the 2-[ 14 C ]deoxyglucose method. The results showed selective metabolic augmentation in rats pretreated with SKF 38393 but not in those pretreated with quinpirole alone or with quinpirole in combination with SKF 38393. These findings demonstrated that dopamine D 1 receptors may play a critical role in the development of metabolic augmentation after repeated stimulant administration.

Cerebral metabolism during propofol anesthesia in humans studied with positron emission tomography.

Although the effects of propofol on cerebral metabolism have been studied in animals, these effects have yet to be directly examined in humans. Consequently, we used positron emission tomography (PET) to demonstrate in vivo the regional cerebral metabolic changes that occur in humans during propofol anesthesia. Six volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism, and the other assessed metabolism during anesthesia with a propofol infusion titrated to the point of unresponsiveness (mean rate +/- SD = 7.8 +/- 1.5 mg.kg-1.h-1). Scans were obtained using the 18fluorodeoxyglucose technique. Awake whole-brain glucose metabolic rates (GMR) averaged 29 +/- 8 mumoles.100 g-1.min-1 (mean +/- SD). Anesthetized whole-brain GMR averaged 13 +/- 4 mumoles.100 g-1.min-1 (paired t test, P < or = 0.007). GMR decreased in all measured areas during anesthesia. However, the decrease in GMR was not uniform. Cortical metabolism was depressed 58%, whereas subcortical metabolism was depressed 48% (P < or = 0.001). Marked differences within cortical regions also occurred. In the medial and subcortical regions, the largest percent decreases occurred in the left anterior cingulate and the inferior colliculus. Propofol produced a global metabolic depression on the human central nervous system. The metabolic pattern evident during anesthesia was reproducible and differed from that seen in the awake condition. These findings are consistent with those from previous animal studies and suggest PET may be useful for investigating the mechanisms of anesthesia in humans.

Dose-dependent effects of chronic amphetamine administration in local cerebral glucose utilization in rat.

The daily dose of amphetamine pretreatment may affect the development of behavioral-sensitized patterns in rodents and amphetamine psychosis in humans. This experiment investigated the regional cerebral metabolic changes in rats after pretreatment with different doses of amphetamine by the 2-[14C]deoxyglucose method. Rates of local cerebral glucose utilization were examined in 37 regions of the rat brain. The result showed generally maximal metabolic augmentation in the 5.0 mg/kg group instead of in the 1.0 or the 10.0 mg/kg groups. Behavioral testing using motor activity cages in rats with the same regimen found no difference among groups. The findings demonstrate that there might be a window effect by daily amphetamine dose on the development of drug dependence and amphetamine psychosis. It was suggested that the 2(-)[14C]deoxyglucose method could be used for further study of animal models of amphetamine psychosis.

Acute d-amphetamine challenge in schizophrenia: Effects on cerebral glucose utilization and clinical symptomatology

The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristics of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however.

Cerebral metabolism, anatomy, and cognition in monozygotic twins discordant for dementia of the Alzheimer type

One pair of monozygotic twins discordant for dementia of the Alzheimer type (DAT) was studied using neuropsychological testing, quantitative x-ray computed tomography (QCT) and magnetic resonance imaging (MRI) of the brain. Cerebral glucose metabolism was measured using positron emission tomography (PET) and 2-[18-F]fluoro-2-deoxy-D-glucose (FDG). The affected twin had a seven year history of progressive cognitive impairment and was severely demented. Neuropsychological testing of the affected twin demonstrated marked deficits in all areas of cognitive function. The asymptomatic twin showed some impairment on tests of perceptual organisation and delayed recall. The affected twin had loss of gray matter and ventricular enlargement on QCT and MRI compared with healthy controls (p less than 0.05). He also had frontal and parietal lobe hypometabolism and increased asymmetry of metabolism on PET compared to both his twin and healthy age-matched controls (p less than 0.05). PET, QCT, and MRI distinguished changes in the twin with DAT compared with his brother and healthy controls. Although the subtle neuropsychological abnormalities of the asymptomatic twin may be signs of early DAT, they were not accompanied by any changes in regional cerebral metabolism or brain structure.