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1.
Neurobiol Aging ; 20(3): 279-85, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10588575

RESUMO

Magnetic resonance imaging (MRI) studies have produced controversial results concerning the correlation of hippocampal volume loss with increasing age. The goals in this study were: 1) to test whether levels of N-acetyl aspartate (NAA, a neuron marker) change in the hippocampus during normal aging and 2) to determine the relationship between hippocampal NAA and volume changes. Proton magnetic resonance spectroscopic imaging (1H MRSI) and MRI were used to measure hippocampal metabolites and volumes in 24 healthy adults from 36 to 85 years of age. NAA/Cho decreased by 24% (r = 0.53, p = 0.01) and NAA/Cr by 26% (r = 0.61, p < 0.005) over the age range studied, whereas Cho/Cr remained stable, implying diminished NAA levels. Hippocampal volume shrank by 20% (r = 0.64, p < 0.05). In summary, aging effects must be considered in 1H MRSI brain studies. Furthermore, because NAA is considered a marker of neurons, these results provide stronger support for neuron loss in the aging hippocampus than volume measurements by MRI alone.


Assuntos
Envelhecimento/metabolismo , Envelhecimento/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Atrofia , Colina/análise , Creatina/análise , Feminino , Hipocampo/química , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prótons , Análise de Regressão
2.
Neurology ; 58(6): 928-35, 2002 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-11914410

RESUMO

BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.


Assuntos
Doença de Alzheimer/metabolismo , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Lobo Parietal/metabolismo , Lobo Temporal/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Análise de Variância , Atrofia , Feminino , Humanos , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/patologia , Lobo Temporal/patologia
3.
Peptides ; 9 Suppl 1: 193-200, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-2856644

RESUMO

Administration of AVP and related peptide fragments following ethanol (EtOH) administration has been shown to enhance retention of tolerance to ethanol. The present studies were designed specifically to: (1) examine the influence of AVP given concurrently with EtOH on the development of tolerance to the ataxic and hypothermic effects of EtOH in Long-Evans rats, and (2) to determine if tolerance to these effects develops in Brattleboro rats which are deficient in AVP. In Experiment 1, EtOH (2.5 g/kg, 15% v/v) was administered IP to 2 groups of rats in combination with a SC injection of either AVP (6 micrograms/kg) or an equal volume of saline. Two additional control groups received IP saline injections in combination with either saline or AVP. After 13 days, EtOH-treated rats were significantly more tolerant than saline-treated animals. AVP significantly increased the hypothermic and ataxic effects of EtOH and failed to enhance tolerance development. AVP delayed the extinction of tolerance to the hypothermic (but not the ataxic) effects of ethanol when administered during the extinction phase to rats previously treated with EtOH. In Experiment 2, Brattleboro rats were injected with EtOH or an equivalent volume of saline and tested for ataxia and hypothermia. Rats receiving EtOH failed to demonstrate significant tolerance to either effect of ethanol after 12 treatment days.


Assuntos
Arginina Vasopressina/fisiologia , Ataxia/induzido quimicamente , Temperatura Corporal/efeitos dos fármacos , Etanol/farmacologia , Animais , Tolerância a Medicamentos , Masculino , Ratos , Ratos Brattleboro , Valores de Referência , Especificidade da Espécie
4.
AJNR Am J Neuroradiol ; 21(4): 621-30, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10782769

RESUMO

BACKGROUND AND PURPOSE: Subcortical ischemic vascular dementia is associated with cortical hypometabolism and hypoperfusion, and this reduced cortical metabolism or blood flow can be detected with functional imaging such as positron emission tomography. The aim of this study was to characterize, by means of MR imaging and 1H MR spectroscopy, the structural and metabolic brain changes that occur among patients with subcortical ischemic vascular dementia compared with those of elderly control volunteers and patients with Alzheimer's disease. METHODS: Patients with dementia and lacunes (n = 11), cognitive impairment and lacunes (n = 14), and dementia without lacunes (n = 18) and healthy age-matched control volunteers (n = 20) underwent MR imaging and 1H MR spectroscopy. 1H MR spectroscopy data were coanalyzed with coregistered segmented MR images to account for atrophy and tissue composition. RESULTS: Compared with healthy control volunteers, patients with dementia and lacunes had 11.74% lower N-acetylaspartate/creatine ratios (NAA/Cr) (P = .007) and 10.25% lower N-acetylaspartate measurements (NAA) in the cerebral cortex (P = .03). In white matter, patients with dementia and lacunes showed a 10.56% NAA/Cr reduction (P = .01) and a 12.64% NAA reduction (P = .04) compared with control subjects. NAA in the frontal cortex was negatively correlated with the volume of white matter signal hyperintensity among patients with cognitive impairment and lacunes (P = .002). Patients with dementia, but not patients with dementia and lacunes, showed a 10.33% NAA/Cr decrease (P = .02) in the hippocampus compared with healthy control volunteers. CONCLUSION: Patients with dementia and lacunes have reduced NAA and NAA/Cr in both cortical and white matter regions. Cortical changes may result from cortical ischemia/infarction, retrograde or trans-synaptic injury (or both) secondary to subcortical neuronal loss, or concurrent Alzheimer's pathologic abnormalities. Cortical derangement may contribute to dementia among patients with subcortical infarction.


Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/metabolismo , Demência Vascular/diagnóstico , Demência Vascular/metabolismo , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Isquemia Encefálica/complicações , Creatina/metabolismo , Demência Vascular/complicações , Feminino , Humanos , Masculino
6.
Dev Psychobiol ; 20(3): 355-63, 1987 May.
Artigo em Inglês | MEDLINE | ID: mdl-3596061

RESUMO

The Genetically Epilepsy-Prone Rat (GEPR) is a widely studied model of epileptiform disorders. While there is considerable evidence that neurotransmitter abnormalities contribute to the unusual sensitivity of these animals to seizures, the possibility that seizure susceptibility may reflect developmental changes in the central nervous system has not been fully addressed. In the present study, 91 GEPR-9 pups were tested for incidence, latency and severity of an audiogenically induced seizure at 6, 9, 12, 15, 18, 21, 24, 27, 28, 29, or 30 days postpartum (1 test per pup) and retested at 60 days. Seizure incidence, latency, and severity were significantly greater on Days 27, 28, 29, and 30 than on all previous days. The first observation of running fits occurred in Day 18 pups and the first evidence of seizures occurred in Day 21 pups. When retested at Day 60, seizure incidence and severity were significantly greater than on initial tests while latency declined. The results suggest that seizure susceptibility in the GEPR-9 occurs as the result of developmental events in the CNS occurring on or shortly after Day 18 postpartum.


Assuntos
Epilepsia/fisiopatologia , Ratos Endogâmicos/genética , Fatores Etários , Animais , Epilepsia/genética , Feminino , Masculino , Ratos
7.
Radiology ; 207(1): 91-102, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9530304

RESUMO

PURPOSE: To replicate previous hydrogen-1 magnetic resonance (MR) spectroscopic imaging findings of metabolic abnormalities in patients with Alzheimer disease (AD), to verify that metabolic abnormalities are not an artifact of structural variations measured at MR imaging, to determine whether metabolic changes correlate with dementia severity, and to test whether MR imaging and MR spectroscopic imaging findings together improve ability to differentiate AD. MATERIALS AND METHODS: MR spectroscopic imaging and MR imaging were performed in 28 patients with AD and 22 healthy elderly subjects. Spectroscopic imaging data were coregistered with MR imaging segmentation data to obtain volume-corrected metabolite concentrations. RESULTS: Consistent with previous results, N-acetyl aspartate (NAA) levels were statistically significantly reduced in frontal and posterior mesial cortex of AD patients, presumably due to neuronal loss. NAA level reductions were independent of structural variations measured at MR imaging and, in parietal mesial cortex, were correlated mildly with dementia severity. Spectroscopic imaging findings of NAA level combined with MR imaging measures did not improve discrimination power for AD relative to that of MR imaging alone. CONCLUSION: Reduced NAA levels in frontoparietal brain are of limited use for diagnosis of AD. However, they are not an artifact of structural variations and thus may provide useful information for the understanding of the pathologic processes underlying AD.


Assuntos
Doença de Alzheimer/diagnóstico , Química Encefálica , Espectroscopia de Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Artefatos , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Colina/análise , Creatina/análise , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade
8.
Magn Reson Med ; 45(3): 513-6, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11241711

RESUMO

The goal of this work was to reexamine previously published (1) brain spectroscopy data of abnormal metabolite ratios in amyotrophic lateral sclerosis (ALS). Toward this goal, (1)H MR spectroscopic imaging data from 10 ALS and nine control subjects were reanalyzed using improved data analysis techniques, including automated curve fitting and tissue-volume correction. In the motor cortex of ALS, N-acetyl aspartate (NAA) was 23% (P = 0.004) lower than in controls, and in the posterior internal capsule of ALS choline compounds (Cho) were 20% (P = 0.02) higher. This demonstrates that the metabolite ratio changes in ALS were due to NAA loss in the motor cortex (as expected) and Cho increase in the posterior internal capsule (not expected). Magn Reson Med 45:513-516, 2001.


Assuntos
Encéfalo/patologia , Metabolismo Energético/fisiologia , Imageamento por Ressonância Magnética , Doença dos Neurônios Motores/diagnóstico , Adulto , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Colina/metabolismo , Creatina/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Cápsula Interna/patologia , Masculino , Pessoa de Meia-Idade , Córtex Motor/patologia , Valores de Referência
9.
Magn Reson Med ; 45(5): 899-907, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11323817

RESUMO

Quantitative measurements of regional and tissue specific concentrations of brain metabolites were measured in elderly subjects using multislice proton magnetic resonance spectroscopic imaging ((1)H MRSI). Selective k-space extrapolation and an inversion-recovery sequence were used to minimize lipid contamination and linear regression was used to account for partial volume problems. The technique was applied to measure the concentrations of N-acetyl aspartate (NAA), and creatine (Cr)- and choline (Cho)-containing compounds in cortical gray and white matter, and white matter lesions of the frontal and the parietal lobe in 40 normal elderly subjects (22 females and 18 males, 56-89 years old, mean age 74 +/- 8). NAA was about 15% lower in cortical gray matter and 23% lower in white matter lesions when compared to normal white matter. Cr was 11% higher in cortical gray matter than in white matter, and also about 15% higher in the parietal cortex than in the frontal cortex. Cho was 28% lower in cortical gray matter than in white matter. Furthermore, NAA and Cr changes correlated with age. In conclusion, regional and tissue differences of brain metabolites must be considered in addition to age-related changes when interpreting (1)H MRSI data.


Assuntos
Envelhecimento/metabolismo , Encefalopatias/metabolismo , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/patologia , Encefalopatias/patologia , Colina/metabolismo , Creatina/metabolismo , Feminino , Humanos , Hidrogênio , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Processamento de Sinais Assistido por Computador
10.
Neurology ; 61(3): 358-64, 2003 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-12913198

RESUMO

OBJECTIVES: 1) To determine the regional pattern of reduced N-acetylaspartate (NAA) in subcortical ischemic vascular dementia (SIVD); 2) to explore the relationship between NAA reduction and subcortical vascular disease; and 3) to test if MR spectroscopic imaging (MRSI) in combination with structural MRI improves differentiation between SIVD and Alzheimer disease (AD). METHODS: Thirteen patients with SIVD (71 +/- 8 years old) and 43 patients with AD of comparable age and dementia severity were studied using MRSI and MRI. Patients were compared to 52 cognitively normal subjects with and without lacunes. RESULTS: Compared to controls, patients with SIVD had lower NAA by 18% (p < 0.001) in frontal cortex and by 27% (p < 0.003) in parietal cortex, but no significant NAA reduction in white matter and medial temporal lobe. Compared to patients with AD, patients with SIVD had lower NAA by 13% (p < 0.02) in frontal cortex and by 20% (p < 0.002) in left parietal cortex. Cortical NAA decreased in SIVD with increasing white matter lesions (r = 0.54, p < 0.02) and number of lacunes (r = 0.59, p < 0.02). Thalamic lacunes were associated with greater NAA reduction in frontal cortex than were lacunes outside the thalamus (p < 0.02) across groups, after adjusting for cognitive impairments. Adding parietal NAA to MRI-derived hippocampal atrophy improved separation between SIVD and AD (p = 0.02) from 79 to 89%. CONCLUSIONS: These results emphasize the importance of cortical dysfunction as a factor in SIVD and indicate a characteristic pattern of metabolite change that might serve as a basis for improved diagnosis.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Demência Vascular/diagnóstico , Demência Vascular/metabolismo , Idoso , Ácido Aspártico/análise , Encéfalo/metabolismo , Encéfalo/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Testes Neuropsicológicos , Valor Preditivo dos Testes , Valores de Referência
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