RESUMEN
BACKGROUND: Previous studies have documented differences in neural activation during language processing in individuals with Down syndrome (DS) in comparison with typically developing individuals matched for chronological age. This study used functional magnetic resonance imaging (fMRI) to compare activation during language processing in young adults with DS to typically developing comparison groups matched for chronological age or mental age. We hypothesised that the pattern of neural activation in the DS cohort would differ when compared with both typically developing cohorts. METHOD: Eleven persons with DS (mean chronological age = 18.3; developmental age range = 4-6 years) and two groups of typically developing individuals matched for chronological (n = 13; mean age = 18.3 years) and developmental (mental) age (n = 12; chronological age range = 4-6 years) completed fMRI scanning during a passive story listening paradigm. Random effects group comparisons were conducted on individual maps of the contrast between activation (story listening) and rest (tone presentation) conditions. RESULTS: Robust activation was seen in typically developing groups in regions associated with processing auditory information, including bilateral superior and middle temporal lobe gyri. In contrast, the DS cohort demonstrated atypical spatial distribution of activation in midline frontal and posterior cingulate regions when compared with both typically developing control groups. Random effects group analyses documented reduced magnitude of activation in the DS cohort when compared with both control groups. CONCLUSIONS: Activation in the DS group differed significantly in magnitude and spatial extent when compared with chronological and mental age-matched typically developing control groups during a story listening task. Results provide additional support for an atypical pattern of functional organisation for language processing in this population.
Asunto(s)
Corteza Cerebral/fisiopatología , Síndrome de Down/fisiopatología , Percepción del Habla/fisiología , Adolescente , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
The participation of the medial temporal cortex and other cerebral structures in the memory impairment that accompanies aging was examined by means of positron emission tomography. Cerebral blood flow (rCBF) was measured during encoding and recognition of faces. Young people showed increased rCBF in the right hippocampus and the left prefrontal and temporal cortices during encoding and in the right prefrontal and parietal cortex during recognition. Old people showed no significant activation in areas activated during encoding in young people but did show right prefrontal activation during recognition. Age-related impairments of memory may be due to a failure to encode the stimuli adequately, which is reflected in the lack of cortical and hippocampal activation during encoding.
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Envejecimiento/fisiología , Corteza Cerebral/fisiología , Hipocampo/fisiología , Memoria/fisiología , Adulto , Anciano , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/diagnóstico por imagen , Femenino , Hipocampo/irrigación sanguínea , Hipocampo/diagnóstico por imagen , Humanos , Masculino , Red Nerviosa/fisiología , Lóbulo Occipital/irrigación sanguínea , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/fisiología , Lóbulo Parietal/irrigación sanguínea , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiología , Corteza Prefrontal/irrigación sanguínea , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Flujo Sanguíneo Regional , Tomografía Computarizada de EmisiónRESUMEN
Polyols are reduction products of aldoses and ketoses; their concentrations in tissues can reflect carbohydrate metabolism. Several polyol species were quantitated in cerebrospinal fluid (CSF) and plasma from 10 Down Syndrome (trisomy 21) subjects between the ages of 22 and 63 years (3 of whom were demented) and from 10 healthy age-matched controls, using a gas chromatographic/mass spectrometric technique. The mean CSF concentration and the mean CSF/plasma concentration ratio of myo-inositol were significantly elevated in Down syndrome compared with controls, but were not correlated with the presence of dementia in the Down subjects. Plasma myo-inositol was not significantly altered in these subjects. No significant difference between Down syndrome and controls was found for CSF concentrations of mannitol, sorbitol, galactitol, ribitol, arabitol, or 1,5-anhydrosorbitol, but plasma mannitol, ribitol and arabitol were elevated in Down syndrome. The present observation provides new impetus for studying synthesis and transport of myo-inositol as well as phosphatidylinositol cycle in trisomy 21 disorder.
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Síndrome de Down/líquido cefalorraquídeo , Inositol/sangre , Alcoholes del Azúcar/sangre , Adulto , Factores de Edad , Anciano , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Demencia/sangre , Demencia/líquido cefalorraquídeo , Demencia/complicaciones , Síndrome de Down/sangre , Síndrome de Down/genética , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Inositol/líquido cefalorraquídeo , Inositol/metabolismo , Masculino , Persona de Mediana Edad , Fosfatidilinositoles/metabolismo , Valores de Referencia , Alcoholes del Azúcar/líquido cefalorraquídeoRESUMEN
To investigate the effects of drug treatment in childhood-onset obsessive-compulsive disorder (OCD), we repeated positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine, two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy. As a group, the patients had a significant improvement on all OCD and anxiety ratings. Positron emission tomography revealed a significant decrease in normalized orbitofrontal regional cerebral glucose metabolism (relative to global metabolism) bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism was directly correlated with two measures of OCD improvement. These results extend previous positron emission tomographic findings of regional dysfunction in OCD and suggest involvement of the orbitofrontal regions in the pathophysiology of OCD.
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Encéfalo/metabolismo , Glucosa/metabolismo , Trastorno Obsesivo Compulsivo/metabolismo , Adulto , Factores de Edad , Encéfalo/fisiopatología , Núcleo Caudado/metabolismo , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Clomipramina/uso terapéutico , Femenino , Fluoxetina/uso terapéutico , Estudios de Seguimiento , Lateralidad Funcional , Giro del Cíngulo/metabolismo , Humanos , Masculino , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/fisiopatología , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Tomografía Computarizada de EmisiónRESUMEN
The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.
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Encéfalo/metabolismo , Glucosa/metabolismo , Trastorno Obsesivo Compulsivo/diagnóstico , Adolescente , Adulto , Ganglios Basales/metabolismo , Ganglios Basales/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Niño , Preescolar , Desoxiglucosa , Femenino , Radioisótopos de Flúor , Lóbulo Frontal/metabolismo , Lóbulo Frontal/fisiopatología , Humanos , Sistema Límbico/metabolismo , Sistema Límbico/fisiopatología , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/metabolismo , Trastorno Obsesivo Compulsivo/fisiopatología , Escalas de Valoración Psiquiátrica , Tomografía Computarizada de EmisiónRESUMEN
Positron emission tomography and 18-F-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 10 adult women with trichotillomania and 20 age-matched female controls. As a group, the patients with trichotillomania showed significantly increased global (mean gray matter) and normalized right and left cerebellar and right superior parietal glucose metabolic rates. Contrary to expectation, this pattern differed from that seen in our previous investigation of obsessive-compulsive disorder. Clomipramine hydrochloride-induced improvement was negatively correlated with anterior cingulate and orbital frontal metabolism, of particular interest because similar results had been obtained for obsessive-compulsive disorder.
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Encéfalo/metabolismo , Glucosa/metabolismo , Tricotilomanía/diagnóstico , Adulto , Encéfalo/diagnóstico por imagen , Cerebelo/metabolismo , Clomipramina/uso terapéutico , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Lóbulo Frontal/metabolismo , Lateralidad Funcional , Giro del Cíngulo/metabolismo , Humanos , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/metabolismo , Lóbulo Parietal/metabolismo , Índice de Severidad de la Enfermedad , Tomografía Computarizada de Emisión , Tricotilomanía/metabolismoRESUMEN
BACKGROUND: There are significant age and sex effects in cognitive ability and brain disease. However, sex differences in aging of human brain areas associated with nonreproductive behavior have not been extensively studied. We hypothesized that there would be significant sex differences in aging of brain areas that subserve speech, visuospatial, and memory function. METHODS: We investigated sex differences in the effect of aging on human brain morphometry by means of volumetric magnetic resonance imaging and on regional cerebral metabolism for glucose by positron emission tomography. In the magnetic resonance imaging study, we examined 69 healthy right-handed subjects (34 women and 35 men), divided into young (age range, 20 to 35 years) and old (60 to 85 years) groups. In the positron emission tomography study, we investigated 120 healthy right-handed subjects (65 women and 55 men) aged 21 to 91 years. RESULTS: In the magnetic resonance imaging study, age-related volume loss was significantly greater in men than women in whole brain and frontal and temporal lobes, whereas it was greater in women than men in hippocampus and parietal lobes. In the positron emission tomography study, significant sex differences existed in the effect of age on regional brain metabolism, and asymmetry of metabolism, in the temporal and parietal lobes, Broca's area, thalamus, and hippocampus. CONCLUSIONS: We found significant sex differences in aging of brain areas that are essential to higher cognitive functioning. Thus, our findings may explain some of the age-sex differences in human cognition and response to brain injury and disease.
Asunto(s)
Envejecimiento/metabolismo , Envejecimiento/fisiología , Encéfalo/anatomía & histología , Encéfalo/metabolismo , Imagen por Resonancia Magnética , Caracteres Sexuales , Tomografía Computarizada de Emisión , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/fisiología , Cognición/fisiología , Femenino , Lóbulo Frontal/anatomía & histología , Lóbulo Frontal/metabolismo , Lóbulo Frontal/fisiología , Glucosa/metabolismo , Hipocampo/anatomía & histología , Hipocampo/metabolismo , Hipocampo/fisiología , Humanos , Masculino , Memoria/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Lóbulo Parietal/anatomía & histología , Lóbulo Parietal/metabolismo , Lóbulo Parietal/fisiología , Factores Sexuales , Percepción Espacial/fisiología , Habla/fisiología , Lóbulo Temporal/anatomía & histología , Lóbulo Temporal/metabolismo , Lóbulo Temporal/fisiologíaRESUMEN
Newborn rats raised on a commercially available iodine-deficient diet developed severe muscle weakness, affecting predominantly their proximal hind limbs, that electrophysiologically and morphologically was determined to be myopathic in type. Follow-up dietary studies, utilizing different combinations of vitamins, minerals, casein and elemental iodine, demonstrated that the myopathy was the result of a deficiency of multiple dietary constituents, particularly casein, and was not due to a deficiency of iodine alone. These findings were compared with those observed in earlier investigations of a variety of nutritional myopathies. In the laboratory study of animals raised on experimental diets, it becomes important to consider the possible contributions of multiple dietary deficiencies in the evaluation of any abnormalities found.
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Yodo/deficiencia , Enfermedades Musculares/metabolismo , Animales , Caseínas/administración & dosificación , Electromiografía , Hipotiroidismo/metabolismo , Minerales/administración & dosificación , Músculos/patología , Enfermedades Musculares/patología , Ratas , Vitaminas/administración & dosificaciónRESUMEN
To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean +/- SD age, 69 +/- 8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross-sectional design. Axial proton-density image slices were analyzed using region-of-interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p less than 0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p less than 0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p less than 0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2-weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI-associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction.
Asunto(s)
Encéfalo/patología , Hipertensión/diagnóstico , Imagen por Resonancia Magnética , Adulto , Anciano , Atrofia , Ventrículos Cerebrales/patología , Líquido Cefalorraquídeo/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Prior studies have indicated abnormal frontal lobes in Down syndrome (DS). The Wisconsin Card Sorting Test (WCST) has been used during functional brain imaging studies to activate the prefrontal cortex. Whether this activation is dependent on successful performance remains unclear. To determine frontal lobe regional cerebral blood flow (rCBF) response in DS and to further understand the effect of performance on rCBF during the WCST, we studied DS adults who perform poorly on this task. METHODS: Initial slope (IS), an rCBF index, was measured with the 133Xe inhalation technique during a Numbers Matching Control Task and the WCST. Ten healthy DS subjects (mean age 28.3 years) and 20 sex-matched healthy volunteers (mean age 28.7 years) were examined. RESULTS: Performance of DS subjects was markedly impaired compared to controls. Both DS and control subjects significantly increased prefrontal IS indices compared to the control task during the WCST. CONCLUSIONS: Prefrontal activation in DS during the WCST was not related to performance of that task, but may reflect engagement of some components involved in the task, such as effort. Further, these results show that failure to activate prefrontal cortex during WCST in schizophrenia is unlikely to be due to poor performance alone.
Asunto(s)
Encéfalo/metabolismo , Circulación Cerebrovascular , Cognición/fisiología , Síndrome de Down/metabolismo , Síndrome de Down/psicología , Adulto , Encéfalo/fisiopatología , Mapeo Encefálico , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Análisis y Desempeño de Tareas , Radioisótopos de XenónRESUMEN
A multiple regression/discriminant analysis of positron emission tomographic cerebral metabolic (rCMRglc) data in 10 obsessive-compulsive disorder (OCD) patients before and during pharmacotherapy was carried out to see if rCMRglc interdependencies distinguished OCD patients from controls. Before therapy, a discriminant function reflecting parietal, sensorimotor, and midbrain rCMRglc interdependencies correctly classified eight (80%) of the 10 patients as OCD; after therapy, six (70%) were classified as controls, most of whom were responders. Before therapy, rCMRglc interdependencies involving basal ganglia, thalamus, limbic, and sensory and association cortical regions distinguished 67% of patients who clinically responded to drug (RESP, n = 6) and 75% of patients who did not (NRESP, n = 4) from controls. After therapy, all RESP were classified as controls; classification of NRESP remained unchanged. The results suggest the conjunctive utility of this method to assess individual differences in rCMRglc during pharmacotherapy, and to explore the neurobiology of OCD.
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Encéfalo/metabolismo , Clomipramina/uso terapéutico , Fluoxetina/uso terapéutico , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Análisis Discriminante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/metabolismo , Análisis de Regresión , Factores de Tiempo , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND: The clinical diagnosis of Alzheimer's disease (AD) can be difficult to make in early stages of disease. Structural neuroimaging offers a potential tool in the clinical diagnosis of AD with mild cognitive impairment. Postmortem studies indicate that early neuropathology in AD occurs in medial temporal lobe limbic structures. Magnetic resonance imaging (MRI) studies that assessed these volumes in mildly impaired AD patients remain inconclusive. METHODS: Using MRI, we measured volumes of left and right hippocampus, amygdala, and anterior and posterior parahippocampal gyrus (PHG) in 13 AD patients with mild cognitive impairment, defined as > or = 20 on the Mini-Mental State Exam, and in 21 healthy age- and sex-matched controls. RESULTS: The AD patients had smaller medial temporal lobe volumes, except for the right anterior PHG. Discriminant function analysis using MRI volumes produced 94% correct group classification. CONCLUSIONS: These results show that in mildly impaired AD patients atrophy is present in medial temporal lobe structures; that MRI volumes of the anterior PHG, which contains entorhinal cortex, are reduced, but the amygdala and hippocampal volumes show greater reduction; and that discriminant function analysis using all volumes as predictors can correctly classify a high proportion of individuals.
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Enfermedad de Alzheimer/patología , Trastornos del Conocimiento/patología , Lóbulo Temporal/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
Using magnetic resonance imaging (MRI), we measured the volumes of various brain structures and cerebrospinal fluid (CSF) in 19 men with dementia of the Alzheimer type (DAT) and 18 healthy age-matched control men. The mean (+/- S.D) Mini-Mental State exam score (MMSE) of the DAT men was 16 +/- 7; 9 were mildly (MMSE > 20), 5 moderately (MMSE 10-20), and 5 severely (MMSE < 10) demented. Brain and CSF volumes were normalized as a percent of the traced intracranial volume to control for the relation of volumes of cerebral structures to head size, and analyzed statistically. The whole group of DAT subjects had significantly smaller mean cerebral brain matter and temporal lobe volumes (p < 0.05), and significantly larger mean ventricular and temporal lobe peripheral CSF volumes than did controls. Mean volumes of the subcortical nuclei did not differ significantly between groups, and mean volume of temporal lobe brain matter decreased significantly more than whole brain, suggesting regional loss of brain matter in DAT. Mildly demented DAT patients had significantly smaller mean cerebral brain matter and temporal lobe volumes and significantly larger volumes of lateral ventricles, and of temporal lobe peripheral CSF, than did controls. Neuropsychological measures of disease severity in DAT patients were significantly (p < 0.05) and appropriately correlated to volumes of cerebral brain matter and right lateral ventricle. These results suggest that in DAT: (i) significant brain atrophy is present early in the disease process, (ii) brain atrophy correlates with severity of cognitive impairment, and (iii) there is greater involvement of the telencephalic association system than whole brain, and there is relative sparing of the caudate, lenticular and thalamic nuclei.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Encéfalo/patología , Líquido Cefalorraquídeo/fisiología , Imagen por Resonancia Magnética/métodos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/patología , Atrofia , Mapeo Encefálico/métodos , Cefalometría/métodos , Ventrículos Cerebrales/patología , Estudios Transversales , Dominancia Cerebral/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Lóbulo Temporal/patologíaRESUMEN
Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.
Asunto(s)
Química Encefálica/fisiología , Hormonas Esteroides Gonadales/fisiología , Síndrome de Turner/fisiopatología , Cromosoma X/fisiología , Adulto , Atrofia , Metabolismo Basal/fisiología , Química Encefálica/genética , Cognición/fisiología , Femenino , Lateralidad Funcional/fisiología , Glucosa/metabolismo , Humanos , Pruebas Neuropsicológicas , Tomografía Computarizada de Emisión , Síndrome de Turner/patología , Síndrome de Turner/psicologíaRESUMEN
Regional CMRglc (rCMRglc) values were measured with [18F]2-fluoro-2-deoxy-D-glucose (18FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized 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 dementia 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/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur.
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Encéfalo/metabolismo , Síndrome de Down/metabolismo , Glucosa/metabolismo , Adulto , Envejecimiento/metabolismo , Desoxiglucosa/análogos & derivados , Femenino , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Humanos , Masculino , Valores de Referencia , Tomografía Computarizada de EmisiónRESUMEN
Correlational analysis of regional cerebral glucose metabolism (rCMRglc) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMRglc interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMRglc interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMRglc interdependencies. We applied this new statistical procedure to resting rCMRglc PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability > 0.70). The results suggest that this statistical approach may be useful for the early detection of AD.
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Enfermedad de Alzheimer/diagnóstico por imagen , Tomografía Computarizada de Emisión , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Análisis Discriminante , Femenino , Fluorodesoxiglucosa F18 , Glucosa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , Factores de Tiempo , Distribución TisularRESUMEN
Etiologically heterogeneous subgroups of patients with Alzheimer's disease (AD) exist and need to be distinguished so as to better identify genetic causes of familial cases. Furthermore, the presence of AD neuropathology in Down syndrome (trisomy 21) subjects older than 35 years suggests that AD in some cases is caused by dysregulation of expression of genes on chromosome 21. Cerebral metabolic abnormalities in life, and the distribution of AD neuropathology in the post-mortem brain, indicate that AD involves the association neocortices and subcortical regions with which they evolved during evolution of the human brain. Accordingly, understanding the molecular basis of this evolution should elucidate the genetic basis of AD, whereas knowing the genetics of AD should be informative about the genomic changes which promoted brain evolution.
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Enfermedad de Alzheimer/genética , Cromosomas Humanos Par 21 , Síndrome de Down/patología , Adulto , Enfermedad de Alzheimer/patología , HumanosRESUMEN
Recent evidence suggests that Alzheimer's disease is an etiologically heterogeneous disorder. A human model of Alzheimer's disease exists that avoids such problems of etiologic heterogeneity. Down syndrome (DS), trisomy 21, is a genetic disorder in which an extra portion of chromosome 21 leads to mental retardation, short stature, and phenotypic abnormalities. Prior investigations by others have shown that DS subjects over 40 years of age demonstrate neuropathologic and neurochemical defects postmortem that are virtually indistinguishable from those found in brains of Alzheimer's disease patients and a universal cognitive deterioration more severe in demented than nondemented older DS subjects. In our study, these nondemented older DS subjects show a distinctive pattern of age-related deficits, while a more global pattern is seen in demented older DS subjects. Dementia occurs in 40% of older DS subjects. We find that in older demented DS subjects positron emission tomography (PET) shows identical patterns of abnormal glucose metabolism as those described previously in Alzheimer's disease patients, selectively involving the phylogenetically newer association areas of parietal and temporal neocortices but sparing primary sensory and motor regions. Further, we find in older demented DS patients quantitative computer-assisted tomography (CT) indicates accelerated neuronal loss and brain atrophy, similar to that previously shown in Alzheimer's disease patients. As a potential use of the DS model, we observed a case of DS with dementia but without mental retardation. This case suggests that expression of dementia in DS may involve genes on chromosome 21 other than in the "obligatory" distal segment of the q arm. Alternatively, differential expression of genes on the q arm of chromosome 21 might cause dementia without phenotypic features and mental retardation.
Asunto(s)
Demencia/diagnóstico por imagen , Síndrome de Down/diagnóstico por imagen , Discapacidad Intelectual/diagnóstico por imagen , Demencia/complicaciones , Demencia/psicología , Síndrome de Down/complicaciones , Síndrome de Down/psicología , Humanos , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/psicología , Tomografía Computarizada de Emisión , Tomografía Computarizada por Rayos XRESUMEN
The rate of production of cerebrospinal fluid (CSF) and the caudorostral gradients of total CSF protein were measured in seven subjects with Down syndrome (DS) and compared to age-matched healthy normal volunteers. The CSF production rate in DS subjects (0.35 +/- 0.02 mL/min.) did not differ significantly from normal subjects (0.37 +/- 0.09 mL/min.). In addition, the caudorostral gradient of total protein was similar in DS and normal subjects, with more caudal fractions of lumbar CSF having higher total protein levels than more rostral fractions. These data suggest that there is no gross disturbance in CSF dynamics in DS.
Asunto(s)
Síndrome de Down/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/líquido cefalorraquídeo , Proteínas del Líquido Cefalorraquídeo/metabolismo , Femenino , Humanos , MasculinoRESUMEN
To assess age-related differences in cortical activation during form perception, two classes of visual textures were shown to young and older subjects undergoing positron emission tomography (PET). Subjects viewed even textures that were rich in rectangular blocks and extended contours and random textures that lacked these organized form elements. Within-group significant increases in regional cerebral blood flow (rCBF) during even stimulation relative to random stimulation in young subjects were seen in occipital, inferior and medial temporal regions, and cerebellum, and in older subjects, in posterior occipital and frontal regions. Group by texture type interactions revealed significantly smaller rCBF increases in older subjects relative to young in occipital and medial temporal regions. These results indicate that young subjects activate the occipitotemporal pathway during form perception, whereas older subjects activate occipital and frontal regions. The between-group differences suggest that age-related reorganization of cortical activation occur during early visual processes in humans.