Visuoconstructive performance and regional cerebral glucose metabolism in Alzheimer's disease

The drawings of Alzheimer's disease (AD) patients and elderly control subjects were rated on a number of specific performance scales, such as attention to configuration, attention to detail, and stimulus boundedness. AD patients showed significantly poorer performance than controls on most drawing scales, and the drawing measures were differentially affected by disease severity. Regional cerebral glucose metabolism (rCMRglc) was assessed via positron emission tomography (PET, with 18FDG) in a subgroup of the AD patients. Partial correlations of rCMRglc with drawing measures (age, sex, and education served as control variables) were conducted. Five out of eight of the drawing measures were significantly correlated (p less than .005) with rCMRglc in occipital and/or temporal-parietal regions, for both left and right hemispheres. Only one of the eight drawing measures, attention to detail, was significantly correlated with rCMRglc in both frontal and posterior regions of interest, again for both hemispheres. Overall dementia severity showed no significant correlations with rCMRglc in any of the regions. These findings are suggestive of a posterior-anterior differentiation, but no left-right hemisphere differentiation, in the relationship between drawing performance and cerebral metabolism in AD, which cannot be accounted for by overall dementia severity. Differences between the drawing performance of AD and unilateral brain damaged patients are discussed, and further applications of the rating scales (provided in the Appendix) are suggested.     

Visuoconstructive performance and regional cerebral glucose metabolism in alzheimer's disease

Abstract

The drawings of Alzheimer's disease (AD) patients and elderly control subjects were rated on a number of specific performance scales, such as attention to configuration, attention to detail, and stimulus boundedness. AD patients showed significantly poorer performance than controls on most drawing scales, and the drawing measures were differentially affected by disease severity. Regional cerebral glucose metabolism (rCMRglc) was assessed via positron emission tomography (PET, with ¹⁸FDG) in a subgroup of the AD patients. Partial correlations of rCMRglc with drawing measures (age, sex, and education served as control variables) were conducted. Five out of eight of the drawing measures were significantly correlated (p < .005) with rCMRglc in occipital and/or temporal-parietal regions, for both left and right hemispheres. Only one of the eight drawing measures, attention to detail, was significantly correlated with rCMRglc in both frontal and posterior regions of interest, again for both hemispheres. Overall dementia severity showed no significant correlations with rCMRglc in any of the regions. These findings are suggestive of a posterior-anterior differentiation, but no left-right hemisphere differentiation, in the relationship between drawing performance and cerebral metabolism in AD, which cannot be accounted for by overall dementia severity. Differences between the drawing performance of AD and unilateral brain damaged patients are discussed, and further applications of the rating scales (provided in the Appendix) are suggested.     

阿尔茨海默病脑白质葡萄糖代谢异常分析

目的探讨阿尔茨海默病(AD)脑白质葡萄糖代谢异常的意义。方法纳入33例符合美国精神障碍诊断与统计手册-第四版(DSM-IV)AD诊断标准的患者和健康对照20名,进行脑正电子发射断层成像(PET)检查。应用SPM软件对PET图像进行分析。结果①与健康对照相比,AD患者有广泛的白质葡萄糖代谢减低,减低较为明显的区域有右侧额叶皮质下白质、左侧额叶上中回皮质下白质(P<0.001);另外,AD患者左侧额叶内侧回皮质下白质、左侧枕叶楔回皮质下白质葡萄糖代谢增强(P<0.001);②与不伴有精神行为症状(BPS)的AD患者(16例)相比,伴有BPS的AD患者(17例)在左右枕叶中回、右侧枕叶楔回、右侧顶下小叶、左侧颞叶梭形回、左侧额叶内侧回等脑区的皮质下白质葡萄糖代谢增强(P<0.001);而左右额叶中央旁回、右侧额叶上回和中回、左侧颞叶上回等脑区的皮质下白质葡萄糖代谢减低(P<0.001)。结论AD有广泛的白质脑葡萄糖代谢异常,有无BPS的AD白质代谢异常不同。     

Diminished glucose transport in Alzheimer's disease: dynamic PET studies

Dynamic positron emission tomography with [18F]fluorodeoxyglucose was used in six patients with Alzheimer's disease (AD) and seven healthy age-matched control subjects to estimate the kinetic parameters K1*, k2*, and k3* that describe glucose transport and phosphorylation. A high-resolution tomograph was used to acquire brain uptake data in one tomographic plane, and a radial artery catheter connected to a plastic scintillator was used to acquire arterial input data. A nonlinear iterative least-squares fitting procedure that included terms for the vascular fraction and time delay to the peripheral sampling site was used to fit a three-compartment model to the brain data. Regions studied included frontal, temporal, occipital, and the entire cortex and subcortical white matter. The values obtained for the individual rate constants and regional CMRglc (rCMRglc; calculated using regional values of the rate constants) were higher than those reported previously. A significant (p less than 0.05) decrease was found in K1* in frontal and temporal cortex in the AD patients compared with the controls, with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex, respectively, of controls and 0.127 and 0.126 ml/g/min in frontal and temporal cortex of the AD patients. rCMRglc was also significantly (p less than 0.02) lower in the AD patients than controls in all cortical brain regions. Lower values of k3* were found in all brain regions in the AD patients, although these were not statistically significant. These findings provide evidence of an in vivo abnormality of forward glucose transport in AD.(ABSTRACT TRUNCATED AT 250 WORDS)     

A volumetric magnetic resonance imaging study of the amygdala in frontotemporal lobar degeneration and Alzheimer's disease

The amygdala is severely atrophied at post-mortem in frontotemporal lobar degeneration (FTLD), and may contribute to the prominent behavioural changes that are early features of FTLD. The aim of this study was to assess amygdala atrophy using MRI in the main syndromic variants of FTLD and Alzheimer's disease (AD). Brain and amygdala volumes, adjusted for intracranial volume, were measured on 46 clinically diagnosed FTLD patients [22 frontal variant FTD (FTD), 14 semantic dementia (SD), 10 progressive non-fluent aphasia (PNFA)], 20 AD patients, and 17 controls. While severe amygdala atrophy was present in both FTLD (41% smaller than controls on the left; 33% on the right) and in AD (22% on the left; 19% on the right), the FTLD group had significantly greater amygdala atrophy (z = 3.21, p = 0.001 left, z = 2.50, p = 0.01 right) and left/right asymmetry (z = 2.03, p = 0.04) than AD. Amygdala atrophy was greater in SD than FTD, PNFA and AD (p < 0.02 for all). Highly asymmetrical atrophy was present in SD, greater on the left (z = 3.23, p = 0.001), and to a lesser extent in PNFA. Despite an overlap between clinical and radiological features of FTLD and AD, marked amygdala atrophy points towards a diagnosis of FTLD, with left greater than right atrophy suggestive of one of the language variants.     

Does Alzheimer's disease affect hippocampal asymmetry? Evidence from a cross-sectional and longitudinal volumetric MRI study

OBJECTIVE: To determine whether Alzheimer's disease (AD) is associated with preferential atrophy of either the left or right hippocampus. METHODS: We examined right-left asymmetry in hippocampal volume and atrophy rates in 32 subjects with probable AD and 50 age-matched controls. Hippocampi were measured on two serial volumetric MRI scans using a technique that minimizes laterality bias. RESULTS: We found a non-significant trend for right > left (R > L) asymmetry in controls at both time points (R > L: 1.7%; CI: -0.3-3.7%; p = 0.1). AD subjects showed a similar non-significant trend for R > L asymmetry at baseline (R > L: 1.8%; CI: -1.9-5.5%; p = 0.32), but not at repeat (p = 0.739). Change in R/L ratio between visits in AD patients was significant (p = 0.02). The AD group had significantly higher variance in these ratios than the controls at baseline (p = 0.02), but not repeat (p = 0.06). AD patients had higher atrophy rates than controls (p < 0.001). Mean (CI) annualized atrophy rates for left and right hippocampi were 1.2% (0.5-1.8%) and 1.1% (0.5-1.8%) for the controls, and 4.6% (3.3-6.0%) and 6.3% (4.9-7.8%) for AD subjects. There was no significant asymmetry in atrophy rates in controls (p = 0.9), but borderline significantly higher atrophy rates in the right hippocampus of the AD group (p = 0.05) compared to the left. Presence of an APOEepsilon4 allele had no significant effect on the size, asymmetry or atrophy rates in AD (p > 0.20). CONCLUSIONS: We report minor R > L asymmetry in hippocampal volumes in controls and present some evidence to suggest that there is a change in the natural R > L asymmetry during the progression of AD.     

Relationship between both IQ and Mini-Mental State Examination and the regional cerebral glucose metabolism in clinically diagnosed Alzheimer's disease: a PET study

In order to clarify the hypofunction in which brain areas demonstrate a decline in Intelligence Quotient (IQ), we examined correlations between the IQ and Mini-Mental State Examination (MMSE) and regional cerebral metabolic rate of glucose (rCMRglc) measured using positron emission tomography (PET) in 26 patients with clinically diagnosed Alzheimer's disease (AD). The MMSE scores and full-scale IQ (FSIQ) showed significant correlations with the rCMRglc in the temporal and parietal lobes on both sides and in the left frontal lobe, which were significantly reduced in comparison to those in the normal controls. A multiple regression analysis showed only the MMSE score to predict verbal IQ (VIQ), performance IQ (PIQ) and FSIQ. VIQ was also predicted by the rCMRglc in the left parietal lobe, while PIQ was predicted by the age at onset. The results suggested MMSE to be an index of dementia severity reflected by general intelligence as shown by IQ in AD, and a reduction in the VIQ can thus be used as an index of the left parietal dysfunction, which is not expressed by MMSE.     

Occipital glucose metabolism in dementia with lewy bodies with and without Parkinsonism: a study using positron emission tomography

Reduction of glucose metabolism in the occipital lobe is reported in dementia with Lewy bodies (DLB) and Parkinson's disease. If dysfunction of the nigrostriatal system is responsible for occipital hypometabolism, (1) DLB patients with parkinsonism would show a lower occipital metabolism than do patients without parkinsonism, and (2) DLB patients without parkinsonism would show an occipital metabolism comparable to those of normal subjects and patients with Alzheimer's disease (AD). To examine these hypotheses, we studied the regional cerebral metabolic rate of glucose (rCMRglc) in patients with a clinical diagnosis of DLB or AD, using (18)F-fluorodeoxyglucose and positron emission tomography. The subjects consisted of 15 DLB patients with parkinsonism, 7 DLB patients without parkinsonism and 7 AD patients without parkinsonism. The medial and lateral occipital rCMRglc was significantly lower in the DLB patients without parkinsonism than in the AD patients. There were no significant differences in occipital metabolic rates between the DLB groups with and without parkinsonism. DLB patients without parkinsonism showed a significant reduction of occipital glucose metabolism which is comparable with that of DLB patients with parkinsonism. The neurobiological bases of occipital hypometabolism in DLB may be pathological processes in the brainstem or basal forebrain structures other than the nigrostriatal system.     

Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease

BackgroundAlthough single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer's disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated.ObjectiveThis study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients.MethodsPatients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups.ResultsCompared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001).ConclusionsDaily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS.     

Reductions in parietal and temporal cerebral metabolic rates for glucose are not specific for Alzheimer''s disease.

Reduction in the regional cerebral metabolic rate for glucose (rCMRglc) in the parietal and temporal regions has been shown in Alzheimer's disease (AD). The specificity of these findings for this disease state is uncertain. We repeatedly measured rCMRglc with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in the resting state in a 68 year old man with slowly progressive dementia who, during life, was initially diagnosed as having dementia of the Alzheimer type, then Parkinson disease with dementia, but was found to have only Parkinson's disease at necropsy. Metabolic ratios (rCMRglc/mean grey CMRglc) were significantly (p < 0.05) reduced in parietal and temporal regions, as well as in the prefrontal and premotor areas. This pattern was similar in regional distribution and magnitude of the defect to that seen in patients with probable AD. These results suggest that reductions of glucose metabolism in association neocortex in AD are not specific to the disease process, but may be related to the dementia state.     

Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological patterns in early dementia of the Alzheimer type

Regional cerebral metabolic rates for glucose (rCMRglc), as measured with positron emission tomography, and neuropsychological function were studied longitudinally (range, 15 to 48 months) in 11 mildly impaired patients with dementia of the Alzheimer type (DAT) and compared with results from patients with moderate and severe DAT and from controls. At initial evaluation, association cortex metabolic asymmetries were greater in patients with DAT than in controls for all dementia severities and correlated significantly with neuropsychological discrepancies between visuospatial and language abilities in patients with moderate dementia. In mildly impaired patients, right-left metabolic asymmetries in the association cortices were directionally stable and became more pronounced over time. At initial evaluation, these patients had significant impairment, relative to controls, on tests of memory and attention to complex tasks but not on tests of language and visuospatial function. Memory, attention, language, and visuospatial impairments, however, all worsened significantly over time. In mildly impaired patients, correlations between right-left metabolic asymmetries and neuropsychological discrepancies were insignificant initially but were significant at last evaluation. These results demonstrate that heterogeneous nonmemory language and visuospatial impairments in early DAT are related to and predicted by the earlier-appearing distribution of metabolic reductions in the association neocortex.     

Topographical analysis of glucose metabolism, as measured with positron emission tomography, in dementia of the Alzheimer type: use of linear histograms

A linear histogram method was employed to analyze brain images of glucose uptake obtained by positron emission tomography in patients with dementia of the Alzheimer type and in control subjects. A line was drawn by computer which traversed the image of a brain slice taken at 70 mm above and parallel to the inferior orbitomeatal line, and rCMRglc was plotted as a function of distance along this line in 3 brain areas: frontal, sensorimotor and parietal. Peak rCMRglc values were significantly decreased in moderately-to-severely demented patients relative to healthy age-matched controls, but not in mildly demented patients. Furthermore, both the mildly and the more severely demented patients differed from controls in having reduced ratios of parietal association to sensorimotor peak rCMRglc. The variances of right-left metabolic asymmetries did not differ significantly between Alzheimer patients and controls. Severity of dementia, as evaluated by scores on the Mini-Mental State Examination, correlated with ratios of peak rCMRglc in frontal and parietal cortex to that in sensorimotor cortex. These results indicate that measures of focal peak rCMRglc do not discriminate between mildly demented patients and controls, whereas focal ratios of rCMRglc, where the denominator corresponds to rCMRglc from a relatively spared region, provide useful measures of metabolic dysfunction in the early stages of Alzheimer's disease.     

The effect of APOE epsilon4 allele on cerebral glucose metabolism in AD is a function of age at onset

BACKGROUND: Although the APOE epsilon4 allele is a well-known risk factor for developing AD, the impact of the epsilon4 allele on clinical manifestations in patients with AD is still controversial. One possible reason for this controversy is that previous studies did not consider the effect of patient age at symptom onset. OBJECTIVE: To investigate the possible impact of patient age at onset of AD on the effect of APOE genotype on regional cerebral glucose metabolism (rCMRglc). METHODS: The authors compared rCMRglc between probable AD patients (based on criteria of the National Institute of Neurologic Disease and Stroke/AD and Related Disorders Association) with APOE epsilon4/4 and APOE epsilon3/3 alleles in early-onset (< or =65 years old) and late-onset (>65 years old) groups. In each group, the patients with APOE epsilon4/4 and APOE epsilon3/3 alleles were comparable for age at onset, age at examination, sex, disease duration, education level, and severity of dementia. RESULTS: In the early-onset group, the patients with the APOE epsilon4/4 genotype showed a significant decrease of rCMRglc in the medial temporal lobe and a significant increase of rCMRglc in the inferior parietal and posterior temporal cortices as compared with those patients with the APOE epsilon3/3 genotype. In the late-onset group, there were no significant differences in the rCMRglc pattern between the patients with APOE epsilon4/4 and APOE epsilon3/3 alleles. CONCLUSIONS: The current findings indicate that the impact of the APOE epsilon4 genotype on cerebral glucose metabolism of patients with AD may be a function of age at symptom onset.     

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.     

Disturbances of spatial vision and object vision correlate differently with regional cerebral glucose metabolism in Alzheimer's disease

There is evidence of two neuronal systems for visual cognition which are referred to as spatial vision and object vision. We subjected 49 patients with mild-to-moderate probable Alzheimer's disease (AD) to tasks associated with these two types of visual cognition. Visual counting was employed as a task to assess visuospatial recognition. Identification of overlapping figures and discrimination of visual forms were used as visuoperceptual tasks that require an ability to recognize objects. Regional cerebral glucose metabolism (rCMRglc) of the subjects was also determined by positron emission tomography. Multivariate statistics controlling for the confounding factors assessed the correlation between the task performances and the rCMRglc. The visual counting score significantly correlated with the metabolic rate of the bilateral inferior parietal lobules. On the other hand, the scores of the visuoperceptual tasks significantly correlated with the metabolic rate of the right middle temporal gyrus and the right inferior parietal lobule. The present study showed that visuospatial disturbance was related to bilateral parietal metabolism, and that visuoperceptual disturbance was related to right temporo-parietal metabolism in patients with mild-to-moderate AD.     

Regional blood-brain glucose transfer and glucose utilization in chronically hyperglycemic, diabetic rats following acute glycemic normalization

Regional rates of brain glucose utilization (rCMRglc) and glucose influx (rJin), along with regional brain tissue glucose concentrations, were measured in chronically hyperglycemic diabetic (CHD) rats following acute glycemic normalization. These results were compared to those obtained in nondiabetic normoglycemic controls. The diabetic rats were evaluated at 6-8 weeks following i.p. streptozotocin injection. All rats were N2O (70%) sedated, paralyzed, and artificially ventilated for study. Acutely normoglycemic (plasma glucose = 8.5 mumol/ml), demonstrated significantly higher (p less than 0.05) rCMRglc and rJin values in 8 of the 11 regions analyzed. Tissue/plasma glucose concentration ratios were significantly greater than control in 9 of 11 regions. Prior to acute glycemic normalization, rCMRglc values in CHD rats were either unchanged or moderately lower than control. These findings indicate that no blood-brain barrier glucose transport repression is present in CHD rats. In fact, the results suggest an increased transport capacity. The increased rCMRglc observed in the acutely normalized CHD rats may be a manifestation of the "hypoglycemic symptoms" observed in chronically hyperglycemic patients following acute glycemic reductions to the normal range. The present results imply that these symptoms are not related to the presence of a relative cerebral glucopenia, as others have suggested.     

The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography.

Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life.     

Grey-matter atrophy in Alzheimer's disease is asymmetric but not lateralized

In Alzheimer's disease (AD), brain atrophy has been proposed to be left lateralized. Here, we reinvestigated the asymmetry and lateralization (i.e., asymmetry directed toward one hemisphere) of grey-matter (GM) distribution in 35 patients with AD, 24 patients with amnestic mild cognitive impairment (aMCI, a state of increased risk for AD), and 30 age-matched healthy controls (HC). We analyzed GM distribution by applying voxel-based morphometry (VBM) including analyses for asymmetry and lateralization. When comparing MCI with AD patients, VBM revealed GM loss in the entorhinal, temporoparietal, dorsofrontal, and occipital cortices as well as in the precuneus; when comparing HCs with MCI patients, we found similar differences, which were less pronounced especially within the temporoparietal cortex and precuneus. Analyses of regional asymmetry and regional lateralization as well as global lateralization did not yield significant results. However, lobar asymmetry of the temporal, parietal, and occipital lobes increased from HC to AD. Moreover, in aMCI and AD patients, performance of language-based neuropsychological tests correlated with lateralization of GM loss to the left hemisphere. We conclude that, in principle, brain atrophy in AD is asymmetric rather than lateralized. At the individual level however, asymmetry contributes to cognitive deficits.     

Clock drawing test in institutionalized patients with schizophrenia compared with Alzheimer's disease patients

The impaired performance of Alzheimer's disease (AD) patients on the clock drawing test (CDT) relative to age-matched normal controls is a well-documented finding in the literature. On the other hand, there is sparse information regarding the use of this test in schizophrenia. We examined three groups of subjects matched for gender and education: institutionalized patients with schizophrenia (n = 32), patients with AD (n = 32), and normal controls (n = 36). The CDT ("free-drawn", "pre-drawn", and three "examiner" conditions) and Mini-Mental State Examination (MMSE) were administered to all participants. In patients with schizophrenia, symptom severity was assessed with the Brief Psychiatric Rating Scale (BPRS). Patients with schizophrenia were significantly younger than AD patients and normal controls (56.78 versus 71.41 and 66.25, respectively), and normal controls had significantly higher MMSE scores than patients with schizophrenia and AD (27.58 versus 20.75 and 18.44, respectively). In all of the clock conditions, the two patient groups performed significantly poorer than the normal controls, with the exception of the "pre-drawn" clock in which AD patients also performed worse than patients with schizophrenia. Age and duration of illness did not correlate significantly with CDT scores. When MMSE scores were used as a covariate, all significant differences on the CDT among the three groups disappeared, with the exception of the "pre-drawn" clock (AD patients had lower scores than both control and schizophrenia groups). In patients with schizophrenia, scores on the BPRS were not related with any CDT variable. Institutionalized patients with schizophrenia and AD patients showed similar deficits on a neuropsychological test sensitive to changes in visual-analytic function, attention, receptive language, and executive functions such as planning, organization, and simultaneous processing.     

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.