A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS.

OBJECTIVE: To study the time-related changes in cerebral metabolic rate of glucose (CMRglc) in MS patients and to correlate these with changes in MRI lesion load and disability. BACKGROUND: Measurements of MRI lesion load and neurologic disability are used widely to monitor disease progression in longitudinal studies of MS patients, but little is known about the associated changes in cerebral neural function. METHODS: The authors studied 10 patients with clinically definite MS who underwent serial measurements of CMRglc, MRI T2-weighted total lesion area (TLA), and clinical evaluation of disability (Expanded Disability Status Scale [EDSS]) over a period of approximately 2 years (three examinations). CMRglc was calculated using PET and 18-fluorodeoxyglucose (FDG). RESULTS: The global cortical CMRglc decreased with time (p<0.001) and the most pronounced reductions of CMRglc were detected in frontal and parietal cortical areas. There was a statistically significant increase of disability (p<0.01) and TLA (p<0.05) measurements during the study, but changes in CMRglc were not correlated to changes in TLA and EDSS. CONCLUSIONS: Global cortical cerebral metabolism in MS is decreased significantly during a 2-year observation period, suggesting a deterioration of cortical activity with disease progression. The time-related changes of cortical CMRglc are statistically stronger than changes in TLA measurements and neurologic disability, and might be a useful secondary measure of treatment efficacy.     

Age, sex and laterality effects on cerebral glucose metabolism in healthy adults

Normal cerebral glucose metabolism (CMRglc) was assessed with positron emission tomography in 66 healthy adults (28 women, 38 men; mean age 39, range 20--69 years) to determine effects of age, sex and laterality on CMRglc using statistical parametric mapping. Significant age-related decreases in global metabolism (gCMRglc) were noted in the entire sample and in both sexes, as well as widespread and bilateral decreases in cortical absolute regional metabolism (rCMRglc) and more focal anterior paralimbic normalized rCMRglc. However, significant positive correlations of age with normalized rCMRglc were observed in cerebellum, thalamus and occipital areas. Although the declines in gCMRglc and rCMRglc with age did not significantly differ between sexes, men compared with women had significantly lower gCMRglc and widespread decreased cortical and subcortical absolute rCMRglc. In the entire sample, and similarly in both sexes, left greater than right asymmetry was observed in medial frontal gyrus, posterior thalamus, lingual gyrus, cuneus and superior cingulate. The opposite laterality appeared in mesio-anterior cerebellum, and lateral frontal and temporal regions. Few regions showed significant interactions of metabolic laterality with either age or sex. These findings contribute toward a convergence in the literature, and the regression models of CMRglc vs. age serve as a normative database to which patients may be compared.     

Frontal cortex atrophy predicts cognitive impairment in multiple sclerosis

The association between regional measures of cortical atrophy and neuropsychological (NP) dysfunction was studied in 35 multiple sclerosis (MS) patients. Patients underwent neurological examination, MRI, and NP testing. Blind quantitative MRI analysis yielded total T(2) lesion area (TLA) and third ventricle width (3VW). Cortical atrophy, rated by blind visual inspection, was more extensive in superior frontal and parietal cortices than in other regions. No MRI measures were correlated with depression scores. TLA and 3VW were significantly correlated with each NP test. Cortical atrophy measures for bilateral superior frontal cortex were retained in regression models predicting impairments in verbal learning, spatial learning, attention, and conceptual reasoning. The authors conclude that cerebral atrophy predicts NP impairment while accounting for the influence of TLA or 3VW. Regions of cortex most susceptible to atrophic and cognitive changes in MS are the right and left superior frontal lobes.     

Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis.

Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular-brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual-integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS.     

Cortical atrophy is relevant in multiple sclerosis at clinical onset

Introduction Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated. Methods 115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed. Results We found a significant global cortical thinning in p-MS (2.22 ± 0.09 mm), RR-MS (2.16 ± 0.10 mm) and SP-MS (1.98 ± 0.11 mm) compared to CIS (2.51 ± 0.11 mm) and HV (2.48 ± 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = −0.393, p = 0.03) and absent in p-MS (r = −0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas. Discussion Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. Received in revised from: 8 August 2006     

Longitudinal study of cognitive dysfunction in multiple sclerosis: neuropsychological,neuroradiological, and neurophysiological findings

OBJECTIVE: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. METHODS: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. RESULTS: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. CONCLUSIONS: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.     

Effects of subcortical cerebral infarction on cortical glucose metabolism and cognitive function.

BACKGROUND: The mechanism of dementia in subcortical cerebral infarction is incompletely understood. OBJECTIVE: To determine how cognitive function is related to cortical metabolism in patients with subcortical infarction and a continuum of cognitive impairment. METHODS: We used positron emission tomography (PET) and the glucose metabolic tracer fludeoxyglucose F 18 to study 8 patients with subcortical stroke and normal cognitive function (S-CN), 5 patients with subcortical stroke and cognitive impairment (S-CI) who did not have dementia, 8 patients with subcortical stroke and dementia (S-D), and 11 controls with no cognitive impairment or stroke. A subset of patients had absolute regional cerebral metabolic rate of glucose (CMRglc) determined, while in all subjects regional tracer uptake normalized to whole brain tracer uptake was calculated. PET data were analyzed by constructing volumes of interest using coregistered magnetic resonance imaging data and correcting the PET data for atrophy. RESULTS: Global CMRglc was significantly lower in the patients with S-D than in the control and S-CN groups, with S-CI rates intermediate to those of the S-D and S-CN groups. Absolute regional CMRs of glucose were similar in the S-D and S-CI groups and in the control and S-CN groups. The regional pattern, however, showed lower right frontal regional CMRglc ratios in all stroke groups compared with the controls. There were modest correlations between performance on the Mini-Mental State Examination and whole brain CMRglc when all 4 groups were included. CONCLUSIONS: These results demonstrate that subcortical infarction produces global cerebral hypometabolism, which is related to the clinical status of the patients. In addition, specific frontal lobe hypometabolism also appears to be a feature of subcortical infarction. Taken together, both global and regional effects on cortical function mediate the production of clinical symptoms in patients with subcortical strokes.     

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.     

Cerebral metabolism in a case of multiple sclerosis with acute mental disorder

Acute mental disorder in early Multiple Sclerosis (MS) is rare and little is known about the structural and metabolic changes in this relation. We present an MS patient with discrete motor and sensory deficits, who developed severe behavioral changes over a period of nine months during the initial course of the disease. The cerebral metabolic rate of glucose (CMRglc) was measured using positron emission tomography (PET), and the patient underwent MRI as well as a comprehensive battery of neuropsychological tests. Significantly reduced values of CMRglc were found bilaterally in the frontal and temporal cortex, the putamen, the thalamus and the hippocampus. The MRI revealed progression of MS lesions in the frontal lobes during the development of mental symptoms. Neuropsychological examination showed wide spread cognitive dysfunction, and a pronounced frontal lobe syndrome. The study demonstrates the remote metabolic effects of lesions affecting subcortical neural connections in an MS patient with severe cognitive dysfunction.     

Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis

Sixty patients with chronic/progressive MS received a newly assembled neuropsychological screening battery (NSB) and a brain MRI. A neuroradiologist blinded to NSB findings quantified cerebral lesions on MRI. We developed weighted brain area lesion scores according to number and size of cerebral lesions. Patients who were impaired on NSB testing had a significantly higher mean bihemispheric lesion score (X = 26.1) than those who were unimpaired (X = 17.4); this MRI lesion rating score correlated significantly with the cognitive summary score of the NSB (r = 0.35, p less than 0.01). However, we did not find a significant correlation between the Kurtzke Expanded Disability Status Scale and any MRI or NSB summary measures. Compared with the Mini-Mental State Exam (MMSE), the NSB cognitive summary score yielded a prevalence estimate for cognitive impairment that is more consistent with previous findings in chronic/progressive MS. The NSB is a useful screening test for cognitive dysfunction in chronic/progressive MS because of its relationship to cerebral lesions on MRI and its greater sensitivity than the frequently used MMSE.     

Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis

Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery-hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were obtained quantitatively. A neuropsychological composite score (NCS) encompassed new learning, attention, working memory, spatial processing and executive function. In each of the regions of interest, the normalized T2 intensity was lower in the MS versus control group (all P<0.001). Regression modelling tested the relative association between all MRI variables and NCS. Globus pallidus T2 hypointensity was the only variable selected in the final model (R2 = 0.301, P = 0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r = -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia T2 hypointensity and BPF demonstrated the strongest associations with cognitive impairment on individual cognitive subtests. Subcortical grey matter T2 hypointensity is related to cognitive impairment in MS, supporting the clinical relevance of T2 hypointensity as a biological marker of MS tissue damage. These data implicate a role for basal ganglia iron deposition in neuropsychological dysfunction.     

Regional cerebral glucose metabolism is normal in young adults with Down syndrome

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.     

MRI T2 hypointensity of the dentate nucleus is related to ambulatory impairment in multiple sclerosis

OBJECTIVES: MRI T2 hypointensity in multiple sclerosis (MS) gray matter, suggesting iron deposition, is associated with physical disability, disease course, lesion load, and brain atrophy. Ambulatory dysfunction limits quality of life; however correlation with conventional MRI remains poor. METHODS: Normalized intensity on T2-weighted images was obtained in the basal ganglia, thalamus, red nucleus, and dentate nucleus in 47 MS patients and 15 healthy controls. Brain T1-hypointense and FLAIR-hyperintense lesion volume, third ventricle width, brain parenchymal fraction and timed 25 foot walk (T25FW) were measured in the MS group. RESULTS: T2 hypointensity was present throughout gray matter in MS vs. controls (all p<0.01). Dentate T2 hypointensity was the only MRI variable significantly correlated with T25FW (Pearson r=-0.355, p=0.007) and was also the best MRI correlate of physical disability (EDSS) score in regression modeling (r=-0.463, R(2)=0.223, p=0.004). CONCLUSIONS: T2 hypointensity is present in subcortical gray matter nuclei in patients with MS vs. normal controls. Dentate nucleus T2 hypointensity is independently related to ambulatory impairment and disability, accounting for more variance than conventional lesion and atrophy measures. This study adds more weight to the notion that T2 hypointensity is a clinically relevant marker of tissue damage in MS.     

Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease

Regional CMRglc (rCMRglc) values were determined with positron emission tomography (PET) in 10 patients with mild to moderate clinically diagnosed Alzheimer's disease (AD) and in 26 healthy controls. rCMRglc in frontal, parietal, and temporal association cortices were significantly more laterally asymmetrical in AD patients than in controls (p less than 0.05). Furthermore, lateral asymmetry of rCMRglc in AD patients but not in the control subjects correlated significantly with asymmetry of language and visuospatial functions such that lower left than right rCMRglc was associated with relatively greater impairment of language and vice versa. The results demonstrate that discrepancies between language and visuospatial deficits in patients with early AD are related to asymmetrical reductions in cerebral cortical glucose metabolism.     

Correlations of brain MRI parameters to disability in multiple sclerosis

OBJECTIVES: The objective was to correlate magnetic resonance imaging (MRI) T2-weighted lesion load and measures of white matter atrophy in the brain to disability in a population-based sample of patients with multiple sclerosis (MS). MATERIAL AND METHODS: A well defined cohort of patients was drawn at random from the general MS population by using the Danish Multiple Sclerosis Registry. A semi-automated local thresholding technique was used to quantify T2-weighted lesions on MRI; whereas manual tracing was applied to measure the corpus callosum brain ratio (CCR) and the ventricle brain ratio (VBR). RESULTS: A sample of 86 patients with a mean age of 43.3 years (SD 4.3), mean disease duration of 13.6 years (SD 4.4) and a median Expanded Disability Status Score (EDSS) of 6.0 was identified. The correlation between total lesion area of the brain (TLA) and disability (EDSS) for the whole sample was moderate (Spearman rank correlation coefficient r=0.48, P<0.001). Also correlations of CCR and VBR to disability (r=0.32-0.46) were significant. CONCLUSIONS: Correlations of TLA and disability in this study were rather strong. Hence, T2-weighted MRI lesion load in the brain still plays an important role as a surrogate marker of disease and as a secondary outcome measure in phase III treatment trials.     

Resting state brain glucose metabolism is not reduced in normotensive healthy men during aging, after correction for brain atrophy

Studies using positron emission tomography (PET) have reported that global and regional values for cerebral blood flow and metabolic rates for glucose (CMRglc and rCMRglc) decline with age in humans. We wished to determine if such decreases could have reflected a partial volume effect (PVE) of cerebral atrophy in the elderly, rather than "intrinsic" reductions per gram brain. We used PET to compare rCMRglc, before and after correcting for the PVE, between 13 healthy older men (aged: 55-82 years) and 11 healthy young men (aged: 22-34 years). PET was performed with 18F-fluoro-2-deoxy-d-glucose while the subjects were in the "resting" state (eyes covered and ears plugged with cotton). The PET scans were normalized to a common brain volume after superimposing them on the subjects' tissue segmented magnetic resonance scans. Analysis showed that rCMRglc in the absence of a PVE correction was significantly less in the older group in insular, frontal, superior temporal cortical, and thalamic regions. Statistical significant differences in rCMRglc, however, were absent after the PVE correction. Thus, statistically significant age reductions in regional brain glucose metabolism, corrected for brain atrophy, are not detectable in healthy normotensive men scanned while in the resting state.     

A short review of cognitive and functional neuroimaging studies of cholinergic drugs: implications for therapeutic potentials

In the last 20 years a cholinergic dysfunction has been the major working hypothesis for the pharmacology of memory disorders. Cholinergic antagonists and lesions impair and different classes of cholinomimetics (i.e. acetylcholine precursors, cholinergic agonists and acetylcholinesterase inhibitors) enhance attention and memory in experiment animals, healthy human subjects and Alzheimer disease patients. In addition, acetylcholinesterase inhibitors improve different cognitive (i.e. visuospatial and verbal) functions in a variety of unrelated disorders such as dementia with Lewy bodies, Parkinson disease, multiple sclerosis, schizoaffective disorders, iatrogenic memory loss, traumatic brain injury, hyperactivity attention disorder and, as we recently reported, vascular dementia and mild cognitive impairment. In animals, different cholinomimetics dose-dependently increased regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF), two indices of neuronal function, more markedly in subcortical regions (i.e. thalamus, hippocampus and visual system nuclei). In both healthy human subjects and Alzheimer disease patients acetylcholinesterase inhibitors increased rCMRglc and rCBF in subcortical and cortical brain regions at rest but attenuated rCBF increases during cognitive performances. Hence, acetylcholinesterase inhibitors may enhance cognition and rCMRglc by acting primarily on subcortical regions that are involved in attentional (i.e. thalamus) and memory (i.e. hippocampus) processes; such an effect probably is not specific for Alzheimer disease and can be beneficial in patients suffering from a wide array of neuropsychiatric disorders.     

Quantitative diffusion weighted magnetic resonance imaging, cerebral atrophy, and disability in multiple sclerosis

OBJECTIVES: To investigate the relations between quantitative diffusion coefficient MRI histograms, clinical variables, and cerebral atrophy. METHODS: Twenty two patients with clinically definite multiple sclerosis and 11 healthy volunteers were studied. Histograms of apparent diffusion coefficient (ADC) from a volume of interest that included multiple slices encompassing the lateral ventricles were processed from diffusion weighted MRI. In addition, total lesion load was measured on T2 weighted dual echo images, and cerebral volume from 3D magnetisation prepared rapid acquisition gradient echo scans. All patients underwent neurological assessment, including disability on the expanded disability status scale (EDSS). RESULTS: Histograms from the patient group showed a reduced peak height and a "right shift" compared with healthy controls. Peak height of the diffusion histogram correlated with both EDSS (r=-0.54, p=0.0101) and disease duration (r=-0.52, p=0.0140), but not with age. Brain volume correlated with peak height of the ADC histogram (r=0.55, p=0.0129), but not with disability. Total lesion load also correlated moderately with EDSS (r=0.46, p=0.03). CONCLUSIONS: This study shows for the first time that quantitative MRI measures of diffusion correlate with clinical variables (disability, disease duration) and cerebral atrophy in multiple sclerosis. Cerebral atrophy and fixed neurological deficit may be attributed to axonal loss, which would be expected to have a significant effect on ADC. Extension of this method to more patients and longitudinal studies will further elucidate its sensitivity, reproducibility, and potential role in clinical practice and treatment trials.     

Decline in cerebral glucose utilisation and cognitive function with aging in Down''s syndrome.

The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years and in 20 healthy men aged 45-64 years. All subjects were at rest with eyes covered and ears plugged. Mean hemispheric CMRglc in the older Down's syndrome subjects was significantly less, by 23%, than in the young Down's syndrome group; statistically significant decreases in regional metabolism (rCMRglc) also were present in all lobar regions. Comparison of the younger control group with the older control group showed no difference in CMRglc or any rCMRglc (p greater than 0.05). Assessment of language, visuospatial ability, attention and memory showed significant reductions in test scores of the old as compared with the young Down's syndrome subjects. These results show that significant age differences in CMRglc and rCMRglc occur in Down's syndrome but not in healthy controls, and that, although only some older Down's syndrome subjects are demented, significant age reductions in neuropsychologic variables occur in all of them.     

健康成人脑葡萄糖代谢的PET研究

目的：探求健康成人脑葡萄糖代谢的变化,及其与性别、年龄的关系。方法：对11例年龄60岁以上（SS）和17例在60岁以下（LS）的两组健康成年人进行正电子发射断层扫描（pstitron emission photography,PET),对各脑区及多个核团进行半定量测定。结果：SS组双侧额叶、眶回、前后扣带回、海马、海马旁回、尾状核、壳核、颞叶、丘脑、岛叶、枕颞外侧回、中央后回、顶叶、颞－顶枕交界区（temorparieto-occiptial,TPO）、杏仁核及左侧枕颞内侧回、左侧中央前回等大脑各部局部脑葡萄糖代谢率（regiona cerebral metabolism rate of glucose,rCMRglc) 较LS组低,其差异具有显著性（P＜0．05或P＜0．01）。相关分析发现,左侧颞叶下加双侧中央前回rCMRglc的变化与增龄无关,提示该部位CMRblc相对稳定,其余脑区均与增龄呈负相关（P＜0．05或P＜0．01）;另外,所有脑区CMRglc的改变均与性别无关（P＞0．05）。结论：健康成年人的大脑代谢和功能随着年龄的增长而减弱,对健康成年人的变化有所了解,方能更好地对异常情况作出正确的判断。