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D Bandy

Publications and source records attributed to D Bandy.

17 recordsLinked to original sources

Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease.

Cross-sectional positron emission tomography (PET) studies find that cognitively normal carriers of the apolipoprotein E (APOE) epsilon4 allele, a common Alzheimer's susceptibility gene, have abnormally low measurements of the cerebral metabolic rate for glucose (CMRgl) in the same regions as patients with Alzheimer's dementia. In this article, we characterize longitudinal CMRgl declines in cognitively normal epsilon4 heterozygotes, estimate the power of PET to test the efficacy of treatments to attenuate these declines in 2 years, and consider how this paradigm could be used to efficiently test the potential of candidate therapies for the prevention of Alzheimer's disease. We studied 10 cognitively normal epsilon4 heterozygotes and 15 epsilon4 noncarriers 50-63 years of age with a reported family history of Alzheimer's dementia before and after an interval of approximately 2 years. The epsilon4 heterozygotes had significant CMRgl declines in the vicinity of temporal, posterior cingulate, and prefrontal cortex, basal forebrain, parahippocampal gyrus, and thalamus, and these declines were significantly greater than those in the epsilon4 noncarriers. In testing candidate primary prevention therapies, we estimate that between 50 and 115 cognitively normal epsilon4 heterozygotes are needed per active and placebo treatment group to detect a 25% attenuation in these CMRgl declines with 80% power and P = 0.005 in 2 years. Assuming these CMRgl declines are related to the predisposition to Alzheimer's dementia, this study provides a paradigm for testing the potential of treatments to prevent the disorder without having to study thousands of research subjects or wait many years to determine whether or when treated individuals develop symptoms.

Aged↗

Effect of satiation on brain activity in obese and lean women.

OBJECTIVE: To investigate the response of the brains of women to the ingestion of a meal. RESEARCH METHODS AND PROCEDURES: We used measures of regional cerebral blood flow (rCBF), a marker of neuronal activity, by positron emission tomography to describe the functional anatomy of satiation, i.e., the response to a liquid meal in the context of extreme hunger (36-hour fast) in 10 lean (BMI < or = 25 kg/m(2); 32 +/- 10 years old, 61 +/- 7 kg; mean +/- SD) and 12 obese (BMI > or = 35 kg/m(2); 30 +/- 7 years old, 110 +/- 14 kg) women. RESULTS: In lean and obese women, satiation produced significant increases in rCBF in the vicinity of the prefrontal cortex (p < 0.005). Satiation also produced significant decreases in rCBF in several regions including the thalamus, insular cortex, parahippocampal gyrus, temporal cortex, and cerebellum (in lean and obese women), and hypothalamus, cingulate, nucleus accumbens, and amygdala (in obese women only; all p < 0.005). Compared with lean women, obese women had significantly greater increases in rCBF in the ventral prefrontal cortex and had significantly greater decreases in the paralimbic areas and in areas of the frontal and temporal cortex. DISCUSSION: This study indicates that satiation elicits differential brain responses in obese and lean women. It also lends additional support to the hypothesis that the paralimbic areas participate in a central orexigenic network modulated by the prefrontal cortex through feedback loops.

Adult↗

Effects of bromocriptine in a patient with crossed nonfluent aphasia: a case report.

OBJECTIVE: Because studies have shown some positive effects of the dopaminergic agent bromocriptine for improving verbal production in patients with nonfluent aphasia, we examined its effect in a patient with an atypical form of crossed nonfluent aphasia from a right hemisphere lesion. DESIGN: Open-label single-subject experimental ABAB withdrawal design. PATIENT: A right-handed man who, after a right frontal stroke, developed nonfluent aphasia, emotional aprosodia, and limb apraxia. INTERVENTION: Escalating doses up to 20mg of bromocriptine in 2 separate phases. MAIN OUTCOME MEASURES: We measured verbal fluency (words/min in discourse, Thurstone letter fluency), expression of emotional prosody, and gesture production. RESULTS: The patient showed substantial improvement in both verbal fluency measures and no significant improvement in gesture or emotional prosody. Verbal fluency improvements continued in withdrawal phases. CONCLUSIONS: Our results are less likely caused by practice or spontaneous recovery because we observed little improvement in emotional prosody and gesture tasks. Verbal fluency improvements during treatment and withdrawal phases suggest that the effects of bromocriptine may be long-lasting in its influence on the neural networks subserving verbal initiation.

Aphasia↗

Thermosensory activation of insular cortex.

Temperature sensation is regarded as a submodality of touch, but evidence suggests involvement of insular cortex rather than parietal somatosensory cortices. Using positron emission tomography (PET), we found contralateral activity correlated with graded cooling stimuli only in the dorsal margin of the middle/posterior insula in humans. This corresponds to the thermoreceptive- and nociceptive-specific lamina I spinothalamocortical pathway in monkeys, and can be considered an enteroceptive area within limbic sensory cortex. Because lesions at this site can produce the post-stroke central pain syndrome, this finding supports the proposal that central pain results from loss of the normal inhibition of pain by cold. Notably, perceived thermal intensity was well correlated with activation in the right (ipsilateral) anterior insular and orbitofrontal cortices.

Adult↗

Differential brain responses to satiation in obese and lean men.

Knowledge of how the brain contributes to the regulation of food intake in humans is limited. We used positron emission tomography and measures of regional cerebral blood flow (rCBF) (a marker of neuronal activity) to describe the functional anatomy of satiation (i.e., the response to a liquid meal) in the context of extreme hunger (36-h fast) in 11 obese (BMI > or =35 kg/m2, age 27+/-5 years, weight 115+/-11 kg, 38+/-7% body fat; mean +/- SD) and 11 lean (BMI < or =25 kg/m2, age 35+/-8 years, weight 73+/-9 kg, 19+/-6% body fat) men. As in lean men, satiation in obese men produced significant increases in rCBF in the vicinity of the ventromedial and dorsolateral prefrontal cortex and significant decreases in rCBF in the vicinity of the limbic/paralimbic areas (i.e., hippocampal formation, temporal pole), striatum (i.e., caudate, putamen), precuneus, and cerebellum. However, rCBF increases in the prefrontal cortex were significantly greater in obese men than in lean men (P < 0.005). rCBF decreases in limbic/paralimbic areas, temporal and occipital cortex, and cerebellum were also significantly greater in obese men than in lean men (P < 0.005), whereas rCBF decreases in the hypothalamus and thalamus were attenuated in obese men compared with lean men (P < 0.05). This study raises the possibility that the brain responses to a meal in the prefrontal areas (which may be involved in the inhibition of inappropriate response tendencies) and limbic/paralimbic areas (commonly associated with the regulation of emotion) may be different in obese and lean men. Additional studies are required to investigate how these differential responses are related to the pathophysiology of obesity.

Adult↗

Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography.

The central role of the hypothalamus in the origination and/or processing of feeding-related stimuli may be modulated by the activity of other functional areas of the brain including the insular cortex (involved in enteroceptive monitoring) and the prefrontal cortex (involved in the inhibition of inappropriate response tendencies). Regional cerebral blood flow (rCBF), a marker of neuronal activity, was measured in 11 healthy, normal-weight men by using positron emission tomography in a state of hunger (after 36-h fast) and a state of satiation (after a liquid meal). Hunger was associated with significantly increased rCBF in the vicinity of the hypothalamus and insular cortex and in additional paralimbic and limbic areas (orbitofrontal cortex, anterior cingulate cortex, and parahippocampal and hippocampal formation), thalamus, caudate, precuneus, putamen, and cerebellum. Satiation was associated with increased rCBF in the vicinity of the ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and inferior parietal lobule. Changes in plasma insulin concentrations in response to the meal were negatively correlated with changes in rCBF in the insular and orbitofrontal cortex. Changes in plasma free fatty acid concentrations in response to the meal were negatively correlated with changes in rCBF in the anterior cingulate and positively correlated with changes in rCBF in the dorsolateral prefrontal cortex. In conclusion, these findings raise the possibility that several regions of the brain participate in the regulation of hunger and satiation and that insulin and free fatty acids may be metabolic modulators of postprandial brain neuronal events. Although exploratory, the present study provides a foundation for investigating the human brain regions and cognitive operations that respond to nutritional stimuli.

Adult↗

Regions of the human brain affected during a liquid-meal taste perception in the fasting state: a positron emission tomography study.

BACKGROUND: The sensation of taste provides reinforcement for eating and is of possible relevance to the clinical problem of obesity. OBJECTIVE: Positron emission tomography (PET) was used to explore regions of the brain that were preferentially affected during the taste perception of a liquid meal by 11 right-handed, lean men in the fasting state. DESIGN: After subjects had fasted for 36 h, 2 measurements of regional cerebral blood flow (rCBF) obtained immediately after subjects retained and swallowed 2 mL of a flavored liquid meal (the taste condition) were compared with 2 measurements of rCBF obtained immediately after subjects retained and swallowed 2 mL of water (the baseline condition). RESULTS: Compared with the baseline condition, taste was associated with increased rCBF (P < 0.005) in the left dorsolateral prefrontal cortex and superior temporal gyrus; the right ventrolateral prefrontal cortex, supramarginal gyrus, and anterior thalamus; and bilaterally in the hippocampal formation, posterior cingulate, midbrain, occipital cortex, and cerebellum. Taste was also associated with decreased rCBF (P < 0.005) in the right dorsolateral prefrontal cortex, superior temporal gyrus, and supplementary motor area, and bilaterally in the medial prefrontal cortex and inferior parietal lobule. CONCLUSIONS: This exploratory study provides additional evidence that the temporal cortex, thalamus, cingulate cortex, caudate, and hippocampal formation are preferentially affected by taste stimulation. The asymmetric pattern of activity in the dorsolateral prefrontal cortex and superior temporal gyrus may contribute to the taste perception of a liquid meal perceived as pleasant. Additional studies are required to determine how these regions are affected in patients with obesity or anorexia.

Adult↗

Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease.

Brain imaging techniques have the potential to characterize neurobiological changes that precede the onset of cognitive impairment in persons at risk for Alzheimer's disease. As previously described, positron emission tomography (PET) was used to compare 11 cognitively normal persons 50 to 62 years of age who were homozygous for the epsilon4 allele of apolipoprotein E and 22 persons without the epsilon4 allele with a reported family history of Alzheimer's dementia who were matched for sex, age, and level of education. The epsilon4 homozygotes had significantly reduced glucose metabolism in the same brain regions as patients with Alzheimer's dementia; the largest reduction was in the posterior cingulate cortex. As described here, magnetic resonance imaging (MRI) was used to compare hippocampal volumes in the same subject groups. The epsilon4 homozygotes showed nonsignificant trends for smaller left and right hippocampal volumes; overall, smaller hippocampal volumes were associated with reduced performance on a long-term memory test. Whereas PET measurements of cerebral glucose metabolism begin to decrease before the onset of memory decline, MRI measurements of hippocampal volume begin to decrease in conjunction with memory decline in cognitively normal persons at risk for Alzheimer's disease.

Aged↗

Noninvasive quantification of the cerebral metabolic rate for glucose using positron emission tomography, 18F-fluoro-2-deoxyglucose, the Patlak method, and an image-derived input function.

The authors developed and tested a method for the noninvasive quantification of the cerebral metabolic rate for glucose (CMRglc) using positron emission tomography (PET), 18F-fluoro-2-deoxyglucose, the Patlak method, and an image-derived input function. Dynamic PET data acquired 12 to 48 seconds after rapid tracer injection were summed to identify carotid artery regions of interest (ROIs). The input function then was generated from the carotid artery ROIs. To correct spillover, the early summed image was superimposed over the last PET frame, a tissue ROI was drawn around the carotid arteries, and a tissue time activity curve (TAC) was generated. Three venous samples were drawn from the tracer injection site at a later time and used for the spillover and partial volume correction by non-negative least squares method. Twenty-six patient data sets were studied. It was found that the image-derived input function was comparable in shape and magnitude to the one obtained by arterial blood sampling. Moreover, no significant difference was found between CMRglc estimated by the Patlak method using either the arterial blood sampling data or the image-derived input function.

Brain↗

Generalized linear least squares method for fast generation of myocardial blood flow parametric images with N-13 ammonia PET.

In this paper, we developed and tested strategies for estimating myocardial blood flow (MBF) and generating MBF parametric images using positron emission tomography (PET), N-13 ammonia, and the generalized linear least square (GLLS) method. GLLS was generalized to the general linear compartment model, modified for the correction of spillover, validated using simulated N-13 ammonia data, and examined using PET data from several patient studies. In comparison to the standard model-fitting procedure, the GLLS method provided similar accuracy and superior computational speed.

Aged↗

Effects of size and orientation change on hippocampal activation during episodic recognition: a PET study.

To determine whether physical match between studied and tested items influences blood flow increases in the hippocampal formation associated with recognition memory, positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while healthy volunteers made old/new judgements about line drawings of objects. Some objects were tested in the same size and orientation as they had appeared earlier during the study phase of the experiment; other objects were tested in a different size or orientation than when they were studied. Blood flow increases in the vicinity of the hippocampal formation were observed in the same object condition compared with the size change and the orientation change conditions, even though recognition accuracy was affected significantly only by orientation change. Results add to previous findings suggesting that physical similarity between studied items and test cues may contribute to hippocampal activation during episodic retrieval.

Adult↗

Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E.

BACKGROUND: Variants of the apolipoprotein E allele appear to account for most cases of late-onset Alzheimer's disease, and persons with two copies of the epsilon 4 allele appear to have an especially high risk of dementia. Positron-emission tomography (PET) has identified specific regions of the brain in which the rate of glucose metabolism declines progressively in patients with probable Alzheimer's disease. We used PET to investigate whether these same regions of the brain are affected in subjects homozygous for the epsilon 4 allele before the onset of cognitive impairment. METHODS: Apolipoprotein E genotypes were established in 235 volunteers 50 to 65 years of age who reported a family history of probable Alzheimer's disease. Neurologic and psychiatric evaluations, a battery of neuropsychological tests, magnetic resonance imaging, and PET were performed in 11 epsilon 4 homozygotes and 22 controls without the epsilon 4 allele who were matched for sex, age, and level of education. An automated method was used to generate an aggregate surface-projection map that compared regional rates of glucose metabolism in the two groups. RESULTS: The epsilon 4 homozygotes were cognitively normal. They had significantly reduced rates of glucose metabolism in the same posterior cingulate, parietal, temporal, and prefrontal regions as in previously studied patients with probable Alzheimer's disease. They also had reduced rates of glucose metabolism in additional prefrontal regions, which may be preferentially affected during normal aging. CONCLUSIONS: In late middle age, cognitively normal subjects who are homozygous for the epsilon 4 allele for apolipoprotein E have reduced glucose metabolism in the same regions of the brain as in patients with probable Alzheimer's disease. These findings provide preclinical evidence that the presence of the epsilon 4 allele is a risk factor for Alzheimer's disease. PET may offer a relatively rapid way of testing future treatments to prevent Alzheimer's disease.

Aged↗

Neuroanatomical correlates of veridical and illusory recognition memory: evidence from positron emission tomography.

Memory distortions and illusions have been thoroughly documented in psychological studies, but little is known about the neuroanatomical correlates of true and false memories. Vivid but illusory memories can be induced by asking people whether they recall or recognize words that were not previously presented, but are semantically related to other previously presented words. We used positron emission tomography to compare brain regions involved in veridical recognition of printed words that were heard several minutes earlier and illusory recognition of printed words that had not been heard earlier. Veridical and illusory recognition were each associated with blood flow increases in a left medial temporal region previously implicated in episodic memory; veridical recognition was distinguished by additional blood flow increases in a left temporoparietal region previously implicated in the retention of auditory/phonological information. This study reveals similarities and differences in the way the brain processes accurate and illusory memories.

Acoustic Stimulation↗