FDG-PET Analysis and Findings in Amnesia Resulting From Hypoxia

Reed, Laurence; Marsden, Paul; Lasserson, Dan; Sheldon, N.; Lewis, Philip D R; Stanhope, Nicola; Guinan, Elizabeth; Kopelman, Michael D.

doi:10.1080/096582199387779

Cited by 50 publications

(41 citation statements)

References 25 publications

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“…As described, medial temporal regions are a major source of projections to the medial parietal͞ posterior cingulate, and their disruption leads to medial parietal͞posterior cingulate hypometabolism in both humans and animals (18,(20)(21)(22)(23)(24). The DAT-related activation in the current study might thus reflect a loss of regulation or functional inhibition.…”

Section: Discussionmentioning

confidence: 82%

“…Studies in both animals and humans show that lesions including the entorhinal and perirhinal cortex lead to reduced posterior cingulate resting metabolism similar to that seen in DAT (20)(21)(22)(23)(24). It has been suggested that posterior cortical regions, in particular, the posterior cingulate and precuneus, may be involved in memory function, and that DATrelated hypometabolism may ref lect memory impairment (25)(26)(27)(28)(29).…”

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confidence: 99%

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Functional deactivations: Change with age and dementia of the Alzheimer type

Lustig

Snyder²,

Bhakta

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

676

508

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Young adults typically deactivate specific brain regions during active task performance. Deactivated regions overlap with those that show reduced resting metabolic activity in aging and dementia, raising the possibility of a relation. Here, the magnitude and dynamic temporal properties of these typically deactivated regions were explored in aging by using functional MRI in 82 participants. Young adults (n ‫؍‬ 32), older adults without dementia (n ‫؍‬ 27), and older adults with early-stage dementia of the Alzheimer type (DAT) (n ‫؍‬ 23) were imaged while alternating between blocks of an active semantic classification task and a passive fixation baseline. Deactivation in lateral parietal regions was equivalent across groups; in medial frontal regions, it was reduced by aging but was not reduced further by DAT. Of greatest interest, a medial parietal͞ posterior cingulate region showed differences between young adults and older adults without dementia and an even more marked difference with DAT. The temporal profile of the medial parietal͞posterior cingulate response suggested that it was initially activated by all three groups, but the response in young adults quickly reversed sign, whereas DAT individuals maintained activation throughout the task block. Exploratory whole-brain analyses confirmed the importance of medial parietal͞posterior cingulate cortex differences in aging and DAT. These results introduce important opportunities to explore the functional properties of regions showing deactivations, how their dynamic functional properties relate to their baseline metabolic rates, and how they change with age and dementia.

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Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 99%

Functional deactivations: Change with age and dementia of the Alzheimer type

Lustig

Snyder²,

Bhakta

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

676

508

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“…Smoothing using a Gaussian kernel of 20 mm was performed to allow for intraindividual differences in gyral anatomy and to increase the signal-to-noise ratio. The effect of variation in whole-brain FDG uptake among different scans from differing injected activities, plasma glucose concentrations, and plasma FDG concentrations, was removed using a voxel-by-voxel analysis of covariance, with values for mean whole-brain uptake as the confounding covariate, analogous to the procedure described by Reed et al (19).…”

Section: Discussionmentioning

confidence: 99%

“…Normalized uptake values for these regions were obtained by dividing the regional uptake values by the whole-brain values, without correcting for injected activity or subject weight. This method has been shown to be a highly sensitive measure of regional variation in FDG uptake (19) Biochemical assays. Plasma glucose was measured at bedside using a glucose oxidase method (Yellow Springs Instruments, Yellow Springs, OH).…”

Section: Discussionmentioning

confidence: 99%

Changes in Regional Brain 18F-Fluorodeoxyglucose Uptake at Hypoglycemia in Type 1 Diabetic Men Associated With Hypoglycemia Unawareness and Counter-Regulatory Failure

et al. 2001

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We examined the effects of acute moderate hypoglycemia and the condition of hypoglycemia unawareness on regional brain uptake of the labeled glucose analog [ 18 F]fluorodeoxyglucose (FDG) using positron emission tomography (PET). FDG-PET was performed in diabetic patients with (n ‫؍‬ 6) and without (n ‫؍‬ 7) hypoglycemia awareness. Each patient was studied at plasma glucose levels of 5 and 2.6 mmol/l, applied by glucose clamp techniques, in random order. Hypoglycemia-unaware patients were asymptomatic during hypoglycemia, with S ymptomatic awareness of minor hypoglycemia is the diabetic patient's main defense against more profound falls in plasma glucose concentrations, to levels low enough to disturb cognitive function. Loss of the ability to recognize early hypoglycemia (hypoglycemia unawareness) is associated with increased incidence of severe hypoglycemia, with sudden confusion or coma (1). Fear of such hypoglycemia limits attempts to maintain strict glycemic control (2), despite clear evidence of its long-term benefits (3).Hypoglycemia unawareness is associated with defects in the normal protective responses to a falling plasma glucose concentration (4). A greater degree of hypoglycemia is required to trigger hormonal and autonomic responses, and the magnitude of responses at any given glucose level is reduced (5). Detection of hypoglycemia and the initiation of counter-regulation is a brain function, and it is suggested that some alteration of brain function at hypoglycemia underlies the defective counter-regulation of hypoglycemia unawareness (6). The effect of hypoglycemia unawareness on the glucose levels associated with the onset of cognitive dysfunction during hypoglycemia in hypoglycemia-unaware patients is controversial, as cognitive functions are differently sensitive to hypoglycemia and show variable changes in sensitivity to hypoglycemia in hypoglycemia unawareness (7,8). This led us to formulate the hypothesis that there would be regional differences in the brain's metabolic responses to acute hypoglycemia between hypoglycemia-aware and -unaware patients.To investigate this, we performed [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans in diabetic men with and without hypoglycemia awareness at euglycemia and hypoglycemia. FDG is an analog of natural glucose (deoxyglucose), labeled with a positron emitter, 18 F. Deoxyglucose is taken up by cells and phosphorylated but then proceeds no further along the intracellular glucose metabolic pathway. Accumulation of labeled deoxyglucose in tissue cells has long been used as a way of measuring glucose uptake in tissue and initial metabolism in many tissues, including the brain (9) The effect of moderate hypoglycemia on the factor (the lumped constant) used to relate the rate of FDG uptake to that of native glucose is uncertain (10). Thus it is not valid, for example, to interpret changes in the rate of wholebrain FDG uptake in hypoglycemia as directly proportional to change in the rate of glucose uptake. The analysis we present her...

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“…A speculative possibility is that these PPC regions represent direct or indirect cortical targets of medial temporal systems contributing to memory. In macaque, medial temporal regions have major reciprocal connections to PPC, notably including zones near area 7a (Suzuki and Amaral, 1994;Clower et al, 2001;Lavenex et al, 2002) and pC/Rsp (Suzuki and Amaral, 1994;Morris et al, 1999;Kobayashi and Amaral, 2003), and their disruption leads to hypometabolism in both humans and animal models (Reed et al, 1999;Millien et al, 2002). Because pathology associated with Alzheimer's disease affects medial temporal regions and processes, a consequence might be the disruption of PPC regions associated with retrieval success.…”

Section: Ppc Participates In Long-term Memory Retrievalmentioning

confidence: 99%

Functional-Anatomic Correlates of Memory Retrieval That Suggest Nontraditional Processing Roles for Multiple Distinct Regions within Posterior Parietal Cortex

Shannon

Buckner²

2004

J. Neurosci.

241

199

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Current theories of posterior parietal cortex (PPC) function emphasize space-based attention and motor intention. Imaging studies of long-term memory have demonstrated PPC activation during successful memory retrieval. Here, we explored the relationship between memory processes and classical notions of PPC function. Study 1 investigated old-new recognition using picture and sound stimuli to test whether PPC memory effects were dependent on visuospatial attention. A region lateral to the intraparietal sulcus [inferior parietal lobule complex (IPLC)] and two regions in the medial PPC [precuneus complex (PCC) and posterior cingulate/retrosplenial cortex (pC/Rsp)] showed strong retrieval success effects for both picture and sound stimuli. Study 2 explored a recognition task with varied response contingencies to investigate whether these retrieval success effects are dependent on motor intentions. In one condition, subjects responded to both old and new items. In two other conditions, subjects responded only to old or only to new items. IPLC, PCC, and pC/Rsp continued to show retrieval success effects with similar magnitudes for all response contingencies, including a condition in which no responses were made to old items. In a third study, IPLC and PCC activity was modulated at retrieval based on levels of processing at study, suggesting sensitivity to memory demands. These studies demonstrate that retrieval success effects in lateral and medial PPC regions are not affected by manipulations predicted by classical theories of PPC function but can be modulated by memory-related manipulations. PPC regions thus have prominent response properties associated with memory, which may arise through interactions with medial temporal cortex.

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FDG-PET Analysis and Findings in Amnesia Resulting From Hypoxia

Cited by 50 publications

References 25 publications

Functional deactivations: Change with age and dementia of the Alzheimer type

Functional deactivations: Change with age and dementia of the Alzheimer type

Changes in Regional Brain 18F-Fluorodeoxyglucose Uptake at Hypoglycemia in Type 1 Diabetic Men Associated With Hypoglycemia Unawareness and Counter-Regulatory Failure

Functional-Anatomic Correlates of Memory Retrieval That Suggest Nontraditional Processing Roles for Multiple Distinct Regions within Posterior Parietal Cortex

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