Moderate doses of alcohol disrupt the functional organization of the human brain

Acute alcohol administration decreases overall brain glucose metabolism, which serves as a marker of brain activity. The behavioral effects of alcohol, however, are likely to reflect not only changes in regional brain activity but also the patterns of brain functional organization. Here we assessed the effects of a moderate dose of alcohol on the patterns of brain activity and cerebral differentiation. We measured brain glucose metabolism in 20 healthy controls with positron emission tomography and fluorodeoxyglucose during baseline and during alcohol intoxication (0.75 g/kg). We used the coefficient of variation (CV) to assess changes in brain metabolic homogeneity, which we used as a marker for cerebral differentiation. We found that alcohol decreased the CV in the brain and this effect was independent of the decrements in overall glucose metabolism. Our study revealed marked disruption in brain activity during alcohol intoxication including decreases in global and regional brain differentiation, a loss of right versus left brain metabolic laterality and a shift in the predominance of activity from cortical to limbic brain regions. The widespread nature of the changes induced by a moderate dose of alcohol is likely to contribute to the marked disruption of alcohol on behavior, mood, cognition and motor activity.     

One-year change in cerebral glucose metabolism in patients with Alzheimer's disease

By using [(18)F]-2-fluoro-deoxy-d-glucose and positron emission tomography, the authors studied changes in regional glucose metabolism after a 1-year interval in patients with mild Alzheimer's disease (AD). Glucose metabolism declined over time in the bilateral precuneus and posterior cingulate gyri and in the frontal, temporal, and parietal cortices. Glucose metabolism in these regions may be a useful measure of the progression of AD and a valid surrogate outcome measure of clinical drug trials.     

Features of regional cerebral glucose metabolism abnormality in corticobasal degeneration

We studied regional cerebral glucose metabolism in 15 patients with a clinical diagnosis of corticobasal degeneration (CBD), 15 patients with probable Alzheimer's disease (AD), and 15 healthy controls for 19 brain regions. Asymmetry in regional glucose metabolism was found in the central and frontal cortices in patients with CBD as compared with either the normal controls or the patients with AD. Regional glucose metabolism in CBD patients was significantly lower in the paracentral and superior parietal areas and thalamus than in patients with AD. Relative glucose metabolism in patients with CBD was significantly higher in the posterior cingulate, medial temporal and basal frontal areas, and significantly lower in the paracentral and superior parietal areas than in those with AD. These features of regional glucose metabolic abnormality in CBD may correspond to neurological and cognitive disturbances peculiar to CBD.     

18FDG PET in vascular dementia: differentiation from Alzheimer's disease using voxel-based multivariate analysis.

The brain metabolic pattern of vascular dementia (VaD) remains poorly characterized. Univariate voxel-based analysis ignores the functional correlations among structures and may lack sensitivity and specificity. Here, we applied a novel voxel-based multivariate technique to a large ((18)F)2-fluoro-2-deoxy-D-glucose positron emission tomography data set. The sample consisted of 153 subjects, one-third each being probable subcortical VaD, probable Alzheimer disease (AD) (matched for Mini-Mental-State examination (MMSE) and age), and normal controls (NCs). We first applied principal component (PC) analysis and removed PCs significantly correlated to age. The remainders were used as feature vectors in a canonical variate analysis to generate canonical variates (CVs), that is, linear combinations of PC-scores. The first two CVs efficiently separated the groups. CV(1) separated VaD from AD with 100% accuracy, whereas CV(2) separated NC from demented subjects with 72% sensitivity and 96% specificity. Images depicting CV(1) and CV(2) showed that lower metabolism differentiating VaD from AD mainly concerned the deep gray nuclei, cerebellum, primary cortices, middle temporal gyrus, and anterior cingulate gyrus, whereas lower metabolism in AD versus VaD concerned mainly the hippocampal region and orbitofrontal, posterior cingulate, and posterior parietal cortices. The hypometabolic pattern common to VaD and AD mainly concerned the posterior parietal, precuneus, posterior cingulate, prefrontal, and anterior hippocampal regions, and linearly correlated with the MMSE. This study shows the potential of voxel-based multivariate methods to highlight independent functional networks in dementing diseases. By maximizing the separation between groups, this method extracted a metabolic pattern that efficiently differentiated VaD and AD.     

Temporal evolution of regional energy metabolism following focal cerebral ischemia in the rat

Focal cerebral ischemia in the rat was induced by occlusion of the left middle cerebral artery. The temporal evolution of regional energy metabolism was studied over the 14 days consequent to the induction of ischemia in the frontal, cingulate, parietal, and occipital cortices as well as in the striatum. Regional concentrations of adenosine triphosphate (ATP), phosphocreatine, and lactate and, in addition, glucose and the cerebral/plasma glucose ratio (C/P) were measured in the hemispheres both ipsilateral and contralateral to the occlusion. Two hours after middle cerebral artery occlusion, the biochemical changes were severe in the striatum and moderate in cortical regions. Later on (at 24 and 48 h), an overall aggravated metabolic status was noted while lactate declined and glucose markedly increased. These latter biochemical changes likely indicate a marked inhibition of the rate of glucose utilization. At 48 h, the energy reserves (ATP, phosphocreatine) of parietal cortex no longer equaled those of other cortical regions, but abruptly fell to the levels found in the striatum without any increase in lactate level. Finally, at 7 and 14 days, the levels of the various metabolites in most cortical regions returned toward control values, although signs of a depressed glucose metabolism remained. However, in both striatum and parietal cortex, ATP and phosphocreatine concentrations, although higher than those observed at 48 h, remained significantly decreased. Our present biochemical study permits the classification of these selected brain regions into three categories. First there are those that are outside the area of infarction: the frontal, cingulate, and occipital cortices. These regions show little temporal evolution of brain energy metabolism but, notwithstanding, they are regions in which glucose use would appear to be greatly depressed. Second is a region considered to be the focus of infarction: the striatum. The caudate-putamen is a region with early and profound metabolic disturbances with no final restitution. Last is the region of metabolic penumbra--the parietal cortex, in which there is a time-related exacerbation of the consequences of middle cerebral occlusion in the rat.     

Reduced glucose metabolism in temporo-parietal cortices of women with borderline personality disorder

Individuals with borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) often experience dissociative symptoms. Evidence is increasing that stress-related hyperglutamatergic states may contribute to dissociative symptoms and neurodegeneration in temporo-parietal cortical areas. Seventeen young women with BPD who had been exposed to severe childhood physical/sexual abuse and presented with pronounced dissociative symptoms underwent (18)fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Nine healthy, matched volunteers served as comparison subjects. Borderline subjects displayed reduced FDG uptake (as analyzed by SPM) in the right temporal pole/anterior fusiform gyrus and in the left precuneus and posterior cingulate cortex. Impaired memory performance among borderline subjects was significantly correlated with metabolic activity in ventromedial and lateral temporal cortices. Our results demonstrate regional hypometabolism in temporal and medial parietal cortical regions known to be involved in episodic memory consolidation and retrieval. Currently, the precuneus/posterior cingulate cortex is modeled as part of a network of tonically active brain regions that continuously gather information about the world around and within us. Decreased resting metabolic rate of these regions may reflect dissociative symptoms and possibly also identity disturbances and interpersonal difficulties of individuals with BPD.     

Abnormalities of regional brain metabolism in Alzheimer's disease and their relation to functional impairment

Resting brain metabolism in patients with Alzheimer's disease (AD) has consistently been demonstrated to be reduced. Moreover, the magnitude of the reduction is related to the severity of dementia. Positron emission tomography (PET), which provides regional metabolic rates for glucose in cross-sectional slices of brain, has demonstrated three alterations in AD that are related to functional deficits. First, whole brain metabolic rate is reduced, and these reductions are related to overall severity of dementia. Second, regional metabolic rates in the association cortices demonstrate relatively greater reductions than are observed in the primary sensory and motor cortices, corresponding to marked impairment of higher cognitive function and relative sparing of sensory and motor function. Third, regional metabolic rates in the association cortices demonstrate increased left-right asymmetry relative to controls. Greater metabolic asymmetry is accompanied by disproportionate neuropsychological deficits in either language or visuospatial function, depending on whether the left or right cerebral hemisphere, respectively, has a lower metabolic rate.     

Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease

Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.     

Cerebral glucose metabolism in dizygotic twin pairs discordant for Alzheimer's disease

Positron emission tomography (PET) with 2-deoxy-2[(18)F]-fluoro-D-glucose (FDG) can be used to estimate regional cerebral glucose metabolism (rCMRgluc). FDG-PET studies have shown rCMRgluc to be reduced especially in temporal and parietal cortices in Alzheimer's disease (AD). A previous study on monozygotic twins discordant for AD showed that the rCMRgluc of the non-demented twins is reduced significantly in the lateral temporal and parietal cortices compared to unrelated controls. In this study we examined 9 pairs of dizygotic twins discordant for AD with FDG-PET. The rCMRgluc of the demented twins was 16% lower in the prefrontal cortex (p = 0.04), 20% lower in the hippocampus (p = 0.002) and 15% lower in the lateral temporal cortex (p = 0.003) compared to controls. The non-demented twins showed no such reductions on any cortical region compared to unrelated control subjects. This implies that both genes and environment, and not genes alone, are causative in the pathogenesis of AD.     

Covarying alterations in Aβ deposition,glucose metabolism,and gray matter volume in cognitively normal elderly

β‐Amyloid (Aβ), a feature of Alzheimer's disease (AD) pathology, may precede reduced glucose metabolism and gray matter (GM) volume and cognitive decline in patients with AD. Accumulation of Aβ, however, has been also reported in cognitively intact older people, although it remains unresolved whether and how Aβ deposition, glucose metabolism, and GM volume relate to one another in cognitively normal elderly. Fifty‐two cognitively normal older adults underwent Pittsburgh Compound B–positron emission tomography (PIB‐PET), [¹⁸F]fluorodeoxyglucose‐PET, and structural magnetic resonance imaging to measure whole‐brain amyloid deposition, glucose metabolism, and GM volume, respectively. Covariance patterns of these measures in association with global amyloid burden measured by PIB index were extracted using principal component analysis–based multivariate methods. Higher global amyloid burden was associated with relative increases of amyloid deposition and glucose metabolism and relative decreases of GM volume in brain regions collectively known as the default mode network including the posterior cingulate/precuneus, lateral parietal cortices, and medial frontal cortex. Relative increases of amyloid deposition and glucose metabolism were also noted in the lateral prefrontal cortices, and relative decreases of GM volume were pronounced in hippocampus. The degree of expression of the topographical patterns of the PIB data was further associated with visual memory performance when controlling for age, sex, and education. The present findings suggest that cognitively normal older adults with greater amyloid deposition are relatively hypermetabolic in frontal and parietal brain regions while undergoing GM volume loss in overlapping brain regions. Hum Brain Mapp 35:297–308, 2014. © 2012 Wiley Periodicals, Inc.     

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Different scales can be used to evaluate dementia severity in Alzheimer’s disease (AD). They do assess different cognitive or functional abilities, but their global scores are frequently in mutual correlation. Functional imaging provides an objective method for the staging of dementia severity. Positron emission tomography was used to assess the relationship between brain metabolism and four dementia scales that reflect a patient’s global cognitive abilities (mini mental state), caregiver’s evaluation of cognitive impairment (newly designed scale), daily living functioning (instrumental activities of daily living) and global dementia (clinical dementia rating). We wondered whether different clinical dementia scales would be related to severity of metabolic impairment in the same brain regions, and might reflect impairment of common cognitive processes. 225 patients with probable AD were recruited in a prospective multicentre European study. All clinical scales were related to brain metabolism in associative temporal, parietal or frontal areas. A factorial analysis demonstrated that all scales could be classified in a single factor. That factor was highly correlated to decrease of cerebral activity in bilateral parietal and temporal cortices, precuneus, and left middle frontal gyrus. This finding suggests that global scores for all scales provided similar information on the neural substrate of dementia severity. Capitalizing on the neuroimaging literature, dementia severity reflected by reduced metabolism in posterior and frontal associative areas in AD might be related to a decrease of controlled processes.     

Cortical surface complexity in frontal and temporal areas varies across subgroups of schizophrenia

Schizophrenia is assumed to be a neurodevelopmental disorder, which might involve disturbed development of the cerebral cortex, especially in frontal and medial temporal areas. Based on a novel spherical harmonics approach to measuring complexity of cortical folding, we applied a measure based on fractal dimension (FD) to investigate the heterogeneity of regional cortical surface abnormalities across subgroups of schizophrenia defined by symptom profiles. A sample of 87 patients with DSM‐IV schizophrenia was divided into three subgroups (based on symptom profiles) with predominantly negative (n = 31), disorganized (n = 23), and paranoid (n = 33) symptoms and each compared to 108 matched healthy controls. While global FD measures were reduced in the right hemisphere of the negative and paranoid subgroups, regional analysis revealed marked heterogeneity of regional FD alterations. The negative subgroup showed most prominent reductions in left anterior cingulate, superior frontal, frontopolar, as well as right superior frontal and superior parietal cortices. The disorganized subgroup showed reductions in bilateral ventrolateral/orbitofrontal cortices, and several increases in the left hemisphere, including inferior parietal, middle temporal, and midcingulate areas. The paranoid subgroup showed only few changes, including decreases in the right superior parietal and left fusiform region, and increase in the left posterior cingulate cortex. Our findings suggest regional heterogeneity of cortical folding complexity, which might be related to biological subgroups of schizophrenia with differing degrees of altered cortical developmental pathology. Hum Brain Mapp 35:1691–1699, 2014. © 2013 Wiley Periodicals, Inc.     

Cortical thickness is associated with poor insight in first-episode psychosis

Through conceptualizing poor insight in psychotic disorders as a form of anosognosia (neurological deficit), frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. Whether non-frontal brain regions are important for insight remains to be investigated. We used a multi-method approach to examine the neural morphometry of all cortical regions for insight in first-episode psychosis. Insight was rated in 79 people with a first-episode psychosis with the awareness of illness and awareness of treatment need and efficacy items of the Scale for assessment of Unawareness of Mental Disorder. Participants were assessed with magnetic resonance imaging. Cortical thickness analysis and voxel-based morphometry were utilized to identify the possible neuroanatomical basis of insight. Cortical thickness technique revealed that poorer awareness of illness was associated with regional thinning in left middle frontal and inferior temporal gyri. Poorer awareness of treatment need and efficacy was associated with cortical thinning in left medial frontal gyrus, precuneus and temporal gyri. No significant associations emerged between any insight measure and gray matter density using voxel-based morphometry. The results confirm predictions derived from the anosognosia/neuropsychology account and assert that regional thickness in frontal cortex is associated with awareness of illness in the early phase of psychosis. The fact that prominent thickness reductions emerged in non-frontal regions of the brain in parietal and temporal cortices for both awareness of illness and awareness of treatment need and efficacy suggests that the neural signature of insight involves a network of brain structures, and not only the frontal lobes as previously suggested.     

Functional imaging of cognition in Alzheimer's disease using positron emission tomography

Positron emission tomography in Alzheimer's disease (AD) demonstrates a metabolic decrease, predominantly in associative posterior cortices (comprising the posterior cingulate cortex), and also involving medial temporal structures and frontal regions at a lesser degree. The level of activity in this wide network is roughly correlated with dementia severity, but several confounds (such as age, education or subcortical ischemic lesions) may influence the brain-behaviour relationship. Univariate analyses allow one to segregate brain regions that are particularly closely related to specific neuropsychological performances. For example, a relationship was established between the activity in lateral associative cortices and semantic performance in AD. The role of semantic capacities (subserved by temporal or parietal regions) in episodic memory tasks was also emphasized. The residual activity in medial temporal structures was related to episodic memory abilities, as measured by free recall performance, cued recall ability and recognition accuracy. More generally, AD patients' performance on episodic memory tasks was correlated with the metabolism in several structures of Papez's circuit (including the medial temporal and posterior cingulate regions). Multivariate analyses should provide complementary information on impaired metabolic covariance in functional networks of brain regions and the consequences for AD patients' cognitive performance. More longitudinal studies are being conducted that should tell us more about the prognostic value of initial metabolic impairment and the neural correlates of progressive deterioration of cognitive performance in AD.     

Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer disease

BACKGROUND: Positron emission tomographic studies of patients with Alzheimer disease (AD) suggest a loss of metabolic functional interactions between different cortical regions. Atrophy of the corpus callosum as the major tract of intracortical connective fibers may reflect decreased cortical functional integration in AD. OBJECTIVES: To investigate whether regional atrophy of the corpus callosum is correlated with regional reductions of cortical glucose metabolism, as shown by positron emission tomography, and whether primary white matter degeneration is a possible cofactor of corpus callosum atrophy in AD. PATIENTS AND METHODS: We measured total and regional cross-sectional areas of the corpus callosum on midsagittal magnetic resonance imaging scans from 12 patients with AD and 15 age-matched control subjects. Regional cerebral metabolic rates for glucose in cortical lobes were measured by positron emission tomography using fludeoxyglucose F 18. White matter hyperintensities were rated in T2-weighted magnetic resonance imaging scans. RESULTS: The total cross-sectional area of corpus callosum was significantly reduced in patients with AD, with the most prominent changes in the rostrum and splenium and relative sparing of the body of the corpus callosum. Frontal and parietal lobe metabolism was correlated with the truncal area of the corpus callosum in AD. The ratios of frontal to parietal and of frontal to occipital metabolism were correlated with the ratio of anterior to posterior corpus callosum area in the group with AD. White matter hyperintensities did not correlate with corpus callosum atrophy in the patients with AD. CONCLUSION: The regional pattern of corpus callosum atrophy correlated with reduced regional glucose metabolism independently of primary white matter degeneration in the patients with AD.     

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.     

Cerebral metabolic correlates of four dementia scales in Alzheimer’s disease

Different scales can be used to evaluate dementia severity in Alzheimer’s disease (AD). They do assess different cognitive or functional abilities, but their global scores are frequently in mutual correlation. Functional imaging provides an objective method for the staging of dementia severity. Positron emission tomography was used to assess the relationship between brain metabolism and four dementia scales that reflect a patient’s global cognitive abilities (mini mental state), caregiver’s evaluation of cognitive impairment (newly designed scale), daily living functioning (instrumental activities of daily living) and global dementia (clinical dementia rating). We wondered whether different clinical dementia scales would be related to severity of metabolic impairment in the same brain regions, and might reflect impairment of common cognitive processes. 225 patients with probable AD were recruited in a prospective multicentre European study. All clinical scales were related to brain metabolism in associative temporal, parietal or frontal areas. A factorial analysis demonstrated that all scales could be classified in a single factor. That factor was highly correlated to decrease of cerebral activity in bilateral parietal and temporal cortices, precuneus, and left middle frontal gyrus. This finding suggests that global scores for all scales provided similar information on the neural substrate of dementia severity. Capitalizing on the neuroimaging literature, dementia severity reflected by reduced metabolism in posterior and frontal associative areas in AD might be related to a decrease of controlled processes. *Both authors contributed equally to this paper. An erratum to this article can be found at .     

Brain gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) in patients with Alzheimer's disease

Summary Activities of Gamma-aminobutyrate aminotransferase (GABA-T) and Monoamine oxidase (MAO)-A and-B were estimated in postmortem brains from 6 control subjects without psychiatric or neurologic disorders and 8 histopathologically verified cases of patients with Alzheimer's disease and senile dementia of Alzheimer type (AD/SDAT). The enzyme activities were examined in four cortical brain regions, three nuclei in the basal ganglia, thalamus and white matter. GABA-T activities in the cortical regions (frontal, parietal, occipital and temporal cortices) and nucleus caudatus were significantly lowered in the AD/SDAT patients. The MAO-A activities were significantly increased in the occipital cortex, caudate nucleus, thalamus and white matter in the AD/SDAT patients. No significant differences were found in the other regions (frontal cortex, parietal cortex, temporal cortex, putamen and globus pallidus). The MAO-B activities in three cortical regions (frontal, parietal and occipital cortices), thalamus and white matter were significantly increased in the AD/SDAT patients, whereas no difference was apparent in the other regions. The changed activities could not be correlated with age or postmortem time. The present results are the first describing decreased GABA-T activities as well as increased MAO-A activities in brain from patients with AD/SDAT, while the results with MAO-B support previous findings. A possible connection was found between the order of magnitude of the changes in enzyme activities and the severity of the disease.     

Comparison of positron emission tomography, cognition, and brain volume in Alzheimer''s disease with and without severe abnormalities of white matter.

OBJECTIVES--To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS--Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS--Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups. CONCLUSIONS--Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.     

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.