Down's Syndrome in Adults: Brain Metabolism

Schwartz, Michael L.; Duara, Ranjan; Haxby, James V.; Grady, Cheryl L.; White, Beverly J.; Kessler, Robert; Kay, Arthur D.; Cutler, Neal R.; Rapoport, Stanley I.

doi:10.1126/science.6224294

Cited by 65 publications

(25 citation statements)

References 20 publications

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“…Global gray CMRglc equaled 8.76 ± 0.76 mg/IOO g/min (mean ± SD) in the DS group as compared with A previous study in our laboratory using positron emission tomography (PET) and eSp]2-fluoro-2-de oxy-D-glucose eSPDG) showed that Down syn drome (DS) adults over the age of 45 years have reductions in parietal and temporal glucose metab olism in comparison with younger DS adults (Scha piro et al, 1987b). However, another study in our laboratory did not find this pattern in four younger DS adults when compared with controls, although these young DS subjects had a mean global increase in glucose metabolism (Schwartz et al, 1983). Be cause this latter study used a calculated correction Gray matter regional measurements also did not differ between groups.…”

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confidence: 67%

“…However, another study in our laboratory did not find this pattern in four younger DS adults when compared with controls, although these young DS subjects had a mean global increase in glucose metabolism (Schwartz et al, 1983). Be cause this latter study used a calculated correction 8.74 ± 1.19 mg/lOO g/min in the control group (p > 0.05).…”

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confidence: 80%

“…The controls, 13 sex-matched, healthy volunteers aged 22-38 years (9 men and 4 women, mean 29.5 years), were participants in the National Institute on Aging Laboratory of Neurosciences Study on Aging (Duara et al, 1983) and were screened with medical, neurological, and laboratory tests. Subjects had no history of neuro logic, psychiatric, or systemic medical disorder.…”

Section: Selection Of Subjectsmentioning

confidence: 99%

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Regional Cerebral Glucose Metabolism is Normal in Young Adults with down Syndrome

Schapiro

Grady

Kumar

et al. 1990

J Cereb Blood Flow Metab

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Summary: Regional CMRglc (rCMRg1c) values were mea sured with ['sF]2-fluoro-2-deoxY-D-glucose eSFDG) and positron emission tomography (PET), using a Scan ditronix PC-1024-7B scanner, in 14 healthy, noninstitu tionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and de mentia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 ± 0.76 mg/IOO g/min (mean ± SD) in the DS group as compared with A previous study in our laboratory using positron emission tomography (PET) and eSp]2-fluoro-2-de oxy-D-glucose eSPDG) showed that Down syn drome (DS) adults over the age of 45 years have reductions in parietal and temporal glucose metab olism in comparison with younger DS adults (Scha piro et al., 1987b). However, another study in our laboratory did not find this pattern in four younger DS adults when compared with controls, although these young DS subjects had a mean global increase in glucose metabolism (Schwartz et al., 1983). Be cause this latter study used a calculated correction Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRg 1C' calculated to reduce the variance associated with abso lute rCMRglc, and rightlleft ratios did not show any con sistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with lsFDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur. Key Words: Brain-Cerebral glucose metabolism-Down syndrome-[ISFj2-Fluoro-2-deoxY-D-glucose-Mental retardation-Positron emission tomography.for attenuation of radiation in the determination of brain radioactivity with PET (Huang et al., 1981), with an ECAT II tomograph, it was possible that the smaller brain size (Schapiro et al., 1987a) and possibly thinner skulls (Roche and Sunderland, 1960) of the DS subjects accounted for the differ ences in cerebral metabolic rates between DS and controls.To avoid this problem and to reevaluate brain metabolism in DS, we investigated cerebral glucose metabolism in a carefully screened, larger group of young adults with trisomy 21, now using a higher resolution PET tomograph (Scanditronix PC-1024-7B) with a measured attenuation correction. This was done to see if there are differences in ab solute cerebral metabolic rate between DS adults and age-matched normals or in patterns of regional metabolism prior to the age of 35-40 years, when Alzheimer disease (AD) neuropathology is reported to occur (Haberland, 1969;Burger and Vogel, 1973;Wisniewski et al., 1985).

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confidence: 67%

mentioning

confidence: 80%

Section: Selection Of Subjectsmentioning

confidence: 99%

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Regional Cerebral Glucose Metabolism is Normal in Young Adults with down Syndrome

Schapiro

Grady

Kumar

et al. 1990

J Cereb Blood Flow Metab

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“…The lower metabolic rate in the most skilled subjects was interpreted as indicating greater neural efficiency. Similarly, patients with Down's syndrome and other forms of mental retardation also show increased global metabolic activity (Cutler, 1986;Haier et al, in press;Schwartz et al, 1983). In the current study, well-educated and highly motivated subjects may have made more effort in executing the task during the second scan when the dementing process had progressed further.…”

Section: Discussionmentioning

confidence: 99%

Glucose metabolic rate and progression of illness in Alzheimer's disease

Siegel

Buchsbaum

Starr

et al. 1995

Int J Geriat Psychiatry

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Thirty‐eight patients with mild to moderate Alzheimer's disease (AD) underwent a neuropsychological test battery and 18‐fluoro‐2‐deoxyglucose (FDG) positron emission tomography (PET) before beginning and at the end of a randomized double‐blind study of an experimental treatment. Twelve of the patients took placebo. In the placebo patients, Mini‐Mental State (MMS) score decreased and cortical metabolism increased significantly over the 6‐month course of the study. Correlations of metabolism with neuropsychological performance were stable over time in the placebo group. Cortical metabolism correlated significantly with performance on the Blessed Information Subtest and the MMS and showed trend correlations with performance on the WAIS Digit Symbol and Word Fluency. Patients with high relative occipital metabolism tended to do poorly on word fluency. Low baseline relative metabolism in right frontal cortex and high baseline relative metabolism in left parietal and temporal cortices and in right occipital cortex predicted more 6‐month deterioration on the World Fluency Test, suggesting that frontal metabolic deficits may precede neuropsychological deficits. Correlations of 6‐month change in MMS, Blessed and Digit Symbol performance with initial glucose metabolism were not significant.

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“…For example, Schwartz et al (1983) in our laboratory, using an ECAT II scanner (Ortec, Life Sciences, Oak Ridge, TN, U.S.A.) and a calculated attenuation correc tion algorithm, reported that regional CMRg 1 c (rCMRglc) was higher in young adult Down syn drome subjects than in controls. However, the dif ference lay not in the subjects but in the calculated attenuation correction, which S. Bacharach and M. Schapiro (unpublished observations) later demon strated overestimates rCMRglc in subjects with small heads, like Down syndrome subjects.…”

Section: A140mentioning

confidence: 99%

Discussion of PET Workshop Reports, Including Recommendations of PET Data Analysis Working Group

Rapoport

1991

J Cereb Blood Flow Metab

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Summary: On May 1-2, 1989, a PET Data Analysis Working Group convened to consider positron emission tomography (PET) methodology and data analysis. The papers presented and the recommendations of the Group are reviewed. The Group recommended that a standard phantom of the human brain be used by different institu tions to examine machine and data reconstruction PET variables. Interinstitutional comparisons could be aided by using a standard three-dimensional coordinate system. Deformations within individual diseased or atypical brains would require nonlinear as well as linear transfor mations to the standard space, using magnetic resonance I shall review some of the issues discussed in this Workshop and shall address related ones. If I refer frequently to work done in the Laboratory of N eu rosciences, National Institute on Aging, it is be cause I am most familiar with this work. I also shall summarize (see Appendix) the recommendations of the PET Data Analysis Working Group, concerning future directions for relevant positron emission to mography (PET) research.In the last 15 years, PET has provided measure ments of metabolism, blood flow, blood-brain bar rier permeability, pH, and receptor distribution within the human brain. Advances have been sub stantial in the three areas discussed in this Work shop: (1) camera development and image recon struction; (2) identification and use of regions of images in register with the PET images. Methods for intersubject averaging of pixel-by-pixel or region of-interest data, as well as appropriate statistical meth ods, need to be developed. PET data may first be explor atory and hypothesis-generating (with less stringent sta tistical theory), then later used to test hypotheses (with more stringent statistical criteria). Common databases, obtained by computer simulation models with known in herent structure, or directly by PET measurements on different groups, could be used to compare analytical and statistical methods among institutions. Key Words: Posi tron emission tomography-Brain metabolism-Imaging.interest (ROIs); and (3) development of experimen tal and statistical models. These accomplishments have allowed us to employ PET to characterize con trol and experimental groups, to distinguish group differences with various degrees of statistical reli ability, and, to a limited extent, to identify individ uals having a brain pattern specific to a disease or behavioral state. Hoffman et al. (1991) summarized recent prog ress in minimizing machine-and technique-related errors, particularly those involving resolution (par tial voluming), dead time (for optimizing kinetic studies), and scatter and attenuation. Their newly developed phantom of the human brain could be used as a reference for interinstitutional compari sons of machine variables (see Appendix). Alpert et al. (1991) calculated that the variance due to the purely technical aspects of PET-resulting from ra dioactive decay and other sources of random er ror-can be reduced to < 10%, by using appropriate transmission co...

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Down's Syndrome in Adults: Brain Metabolism

Cited by 65 publications

References 20 publications

Regional Cerebral Glucose Metabolism is Normal in Young Adults with down Syndrome

Regional Cerebral Glucose Metabolism is Normal in Young Adults with down Syndrome

Glucose metabolic rate and progression of illness in Alzheimer's disease

Discussion of PET Workshop Reports, Including Recommendations of PET Data Analysis Working Group

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