In 76 normal volunteers studied by positron emission tomography, with [18F]fluorodeoxyglucose, CMRglu was significantly lower in the elderly as compared with young subjects and significantly higher in females relative to males. However, in 58 of these subjects who also had magnetic resonance imaging scans, age and gender were found to be unrelated to CMRglu, when the effects of brain volume and brain atrophy on CMRglu were partialed out using covariate analyses. Individually, brain volume was found to have a significant effect on CMRglu, explaining approximately 17% of the variability in CMRglu measures and brain atrophy explaining approximately 8% of the variance in CMRglu. Together these two measures accounted for approximately 21% of the variance. Cerebrovascular risk factors in normal subjects were not found to affect mean CMRglu or the variability of CMRglu measures. In this study almost 80% of the variance in CMRglu could not be explained by any of the factors that had been considered. This implies a lack of sensitivity of absolute values of global CMRglu to the mild effects of brain dysfunction. Although some of the unexplained variance is probably methodological in origin, physiological factors that are difficult to quantify, such as the state of arousal, are likely to be contributory as well.

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To investigate local metabolic and hemodynamic interrelationships during functional activation of the brain, paired studies of local cerebral glucose utilization (lCMRGlc) and blood flow (lCBF) were carried out in 10 normal subjects (9 right-handed, 1 ambidextrous) at rest and during a unilateral discriminative somatosensory/motor task--palpation and sorting of mah-jongg tiles by engraved design. The extent of activation was assessed on the basis of percentage difference images following normalization to compensate for global shifts. The somatosensory stimulus elevated lCMRGlc by 16.9 +/- 3.5% (mean +/- standard deviation) and lCBF by 26.5 +/- 5.1% in the contralateral sensorimotor cortical focus; smaller increments were noted in the homologous ipsilateral site. The increments of lCMRGlc and lCBF correlated poorly with one another in individual subjects. Stimulation of the right hand resulted in significantly higher contralateral lCMRGlc activation (19.6%) than did stimulation of the left hand (14.1%) (p less than 0.005), whereas the lCBF response was independent of the hand stimulated. Our results indicate that both glycolytic metabolism and blood flow increase locally with the execution of an active sensorimotor task and suggest that both measures may serve as reliable markers of functional activation of the normal brain.

Summary: Variability in cerebral glucose metabolism was examined between and within subjects when paired studies were performed in the resting state or in a behav iorally activated state. Both normal and demented sub jects were studied twice each, from I to 6 weeks apart, under near-identical conditions, using positron emission tomography (PET) and [18Flfluorodeoxyglucose. Resting state studies were repeated in nine normal and four de mented subjects. A picture-viewing test, used for activa tion during PET, was used repeatedly in seven normal and five demented subjects. Within-subject variability, as assessed by the percent difference in metabolic rates inThe clinical applications of positron emission to mography (PET) have been relatively limited com pared, for example, to the applications of magnetic resonance imaging in routine clinical management. One factor contributing to the restriction of the clinical use of PET is the large variability, and therefore reduced reliability, of measures of cere bral blood flow and metabolism in normal subjects and patients with a variety of clinical disorders. As PET is an effective method of examining the re gional cerebral effects of behavioral activation, it is of importance to determine whether variability of PET measures increases or decreases when specific states of behavioral activation are used. The pur pose of this study is to demonstrate that the vari ability of cerebral metabolic rate for glucose (CMRg1u) can be reduced by performing studies in specific states of behavioral activation. The vari ability of CMRg1u was studied in psychologically ac tivated states and in nonactivated or resting states, in normal and demented subjects. We show that studies done with behavioral activation, rather than in the resting state, result in reduced intraindividual variability. MATERIALS AND METHODS SubjectsSubjects studied were enrolled into two groups. These comprised elderly normals and patients with dementia who were age-matched to the elderly normal group as closely as possible. Sixteen normal subjects and nine pa tients with dementia were screened for systemic, cardio vascular, renal, and endocrine disorders by physical ex amination, electrocardiography, chest x-ray, and routine laboratory screening, as previously described (Duara et aI., 1983). All normal subjects and patients underwent