Demonstration of decreased posterior cingulate perfusion in mild Alzheimer's disease by means of H2 15O positron emission tomography

Ishii, Kazunari; Sasaki, Masahiro; Yamaji, Shigeru; Sakamoto, Setsu; Kitagaki, Hajime; Mori, Etsuro

doi:10.1007/bf00841407

Cited by 61 publications

(40 citation statements)

References 8 publications

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“…Alternatively, it is also possible that we are observing the direct effect of AD pathology itself: decreased rCBF or rCMRglc has been reported to co-localize with areas where AD-related neuropathological changes occur and is therefore considered to represent an in vivo index of the effect of the neuropathological process on brain function. The cingulate, inferior parietal lobule and supramarginal gyrus, which are pathologically affected and manifest decreased rCBF or rCMRglc early in AD in univariate analyses (Hoffman et al, 2000;Ishii et al, 1997;Kennedy et al, 1995;Minoshima et al, 1997;Silverman et al, 2001), also showed concomitant decreased rCBF in our study. However, medial temporal areas like the parahippocampal gyrus, which is also pathologically affected and manifests decreased rCBF or rCMRglc early in AD in univariate analyses, exhibited concomitant increased flow in our covariance pattern.…”

Section: Multivariate Analyses Resting Data and Biopathological Conssupporting

confidence: 77%

“…In the literature of voxel-wise analyses, reduced rCBF in temporal, parietal and cingulate cortex has been noted in AD patients in comparison to controls (Ishii et al, 1997;Kennedy et al, 1995;Minoshima et al, 1997;Salmon et al, 2000;Signorini et al, 1999). With the exception of one study (Ishii et al, 1997), all other previous reports included moderate-or even advanced-stage AD patients (Kennedy et al, 1995;Minoshima et al, 1997;Salmon et al, 2000;Signorini et al, 1999).…”

Section: Ad-control Discriminationmentioning

confidence: 94%

“…Regional cerebral blood flow (rCBF) or regional cerebral glucose metabolism (rCMRglc) deficits have been documented in patients with Alzheimer's disease (AD) either via expert clinical reading (Hoffman et al, 2000;Silverman et al, 2001) or statistical methods (usually region of interest analyses or more rarely voxel-wise analyses, Ishii et al, 1997;Kennedy et al, 1995;Minoshima et al, 1997;Salmon et al, 2000;Signorini et al, 1999). Both rCBF and rCMRglc are reliable indices of neuronal/synaptic function (Jueptner and Weiller, 1995) and are considered to provide a valuable in vivo index of the effects of the neuropathological process on brain function in patients with AD.…”

Section: Introductionmentioning

confidence: 99%

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Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance

et al. 2004

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Although multivariate analytic techniques might identify diagnostic patterns that are not captured by univariate methods, they have rarely been used to study the neural correlates of Alzheimer's disease (AD) or cognitive impairment. Nonquantitative PET scans were acquired during rest in 17 probable AD subjects selected for mild severity [mean-modified Mini Mental Status Examination (mMMS) 46/57; SD 5.1], 16 control subjects (mMMS 54; SD 2.5) and 23 subjects with minimal to mild cognitive impairment but no dementia (mMMS 53; SD 2.8). Expert clinical reading had low success in discriminating AD and controls. There were no significant mean flow differences among groups in traditional univariate SPM Voxel-wise analyses or region of interest (ROI) analyses. A covariance pattern was identified whose mean expression was significantly higher in the AD as compared to controls (P = 0.03; sensitivity 76-94%; specificity 63-81%). Sites of increased concomitant flow included insula, cuneus, pulvinar, lingual, fusiform, superior occipital and parahippocampal gyri, whereas decreased concomitant flow was found in cingulate, inferior parietal lobule, middle and inferior frontal, supramarginal and precentral gyri. The covariance analysis-derived pattern was then prospectively applied to the cognitively impaired subjects: as compared to subjects with Clinical Dementia Rating (CDR) = 0, subjects with CDR = 0.5 had significantly higher mean covariance pattern expression (P = 0.009). Expression of this pattern correlated inversely with Selective Reminding Test total recall (r = −0.401, P = 0.002), delayed recall (r = −0.351, P = 0.008) and mMMS scores (r = −0.401, P = 0.002) in all three groups combined. We conclude that patients with AD may differentially express resting cerebral blood flow covariance patterns even at very early disease stages. Significant alterations in expression of resting flow covariance patterns occur even for subjects with cognitive impairment. Expression of covariance patterns correlates with cognitive and functional performance measures, holding promise for meaningful associations with underlying biopathological processes.

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Section: Multivariate Analyses Resting Data and Biopathological Conssupporting

confidence: 77%

Section: Ad-control Discriminationmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance

et al. 2004

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“…Indeed, PET and MRI studies showed that the severity of AD symptoms is correlated with hypometabolism in PCC but not temporal regions (Ishii et al, 1997;Hirono et al, 1998;Alsop et al, 2000). Cammalleri et al (1996) described a patient with a tumor in the PCC who was unable to navigate in its surroundings due to the inability to use landmarks for route finding.…”

Section: Introductionmentioning

confidence: 99%

Animal model of posterior cingulate cortex hypometabolism implicated in amnestic MCI and AD

Riha

Rojas

Colorado³

et al. 2008

Neurobiology of Learning and Memory

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The posterior cingulate cortex (PCC) is the brain region displaying the earliest sign of energy hypometabolism in patients with amnestic mild cognitive impairment (MCI) who develop Alzheimer's disease (AD). In particular, the activity of the mitochondrial respiratory enzyme cytochrome oxidase (C.O.) is selectively inhibited within the PCC in AD. The present study is the first experimental analysis designed to model in animals the localized cortical C.O. inhibition found as the earliest metabolic sign of early-stage AD in human neuroimaging studies. Rats were used to model local inhibition of C.O. by direct injection of the C.O. inhibitor sodium azide into the PCC. Learning and memory were examined in a spatial holeboard task and brains were analyzed using quantitative histochemical, morphological and biochemical techniques. Behavioral results showed that sodium azide-treated rats were impaired in their memory of the baited pattern in probe trials as compared to their training scores before treatment, without non-specific behavioral differences. Brain analyses showed that C.O. inhibition was specific to the PCC, and sodium azide increased lipid peroxidation, gliosis and neuron loss, and lead to a network functional disconnection between the PCC and interconnected hippocampal regions. It was concluded that impaired memory by local C.O. inhibition in the PCC may serve to model in animals a metabolic lesion similar to that found in patients with amnestic MCI and early-stage AD. This model may be useful as an in vivo testing platform to investigate neuroprotective strategies to prevent or reduce the amnestic effects produced by posterior cingulate energy hypometabolism.

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“…This greater hypometabolism determined by PET is not merely an artifact of generalized atrophy (Ibanez et al, 1998) or AD histopathology that is lower in PCC than the other regions (Braak and Braak, 1998), although degeneration of PCC occurs in AD (Brun and Gustafson, 1976). Severity of AD symptoms is correlated with hypoactivity in PCC but not temporal regions, as measured with PET and magnetic resonance imaging (Ishii et al, 1997;Hirono et al, 1998;Alsop et al, 2000). PCC hypoperfusion was also shown by subjects with only questionable dementia who later converted to AD in longitudinal SPECT studies (Johnson et al, 1998;Kogure et al, 2000).…”

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confidence: 95%

Energy Hypometabolism in Posterior Cingulate Cortex of Alzheimer's Patients: Superficial Laminar Cytochrome Oxidase Associated with Disease Duration

2001

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Among brain regions affected in Alzheimer's disease (AD), the posterior cingulate shows the earliest and largest decrement in energy metabolism. Positron emission tomography (PET) studies have shown that these decrements appear before the onset of memory deficits or other symptoms in persons at genetic risk for AD. This study compares in vivo imaging results and in situ postmortem analyses by examining the posterior cingulate (area 23) in 15 AD patients and 13 age-matched nondemented controls using quantitative cytochrome oxidase histochemistry as an intracellular measure of oxidative energy metabolic capacity. Each of the six layers of the posterior cingulate demonstrated a decline in cytochrome oxidase activity in AD relative to controls, whereas adjacent motor cortex showed no significant differences. This decrement did not appear to be mainly secondary to nonspecific decrement in mitochondrial enzymes, oxidative stress, cell loss, or histopathology. The cytochrome oxidase decrement was most severe in the superficial layer I (Ϫ39%), which demonstrated a correlation to disease duration. Covariance analyses suggest that superficial laminas undergo a functional uncoupling from the deeper layers of posterior cingulate cortex in AD, whereas no such effects are found in motor cortex or controls. These findings expand on previous results from PET studies by illuminating the layer-specific cytochrome oxidase contributions to energy hypometabolism. The findings suggest a decrement of cytochrome oxidase in posterior cingulate cortex, with progressive reduction within the superficial laminas linked to disease duration. Such decrement could contribute to some of the behavioral symptoms displayed by AD patients. This decrement appeared greater in women.Key words: cytochrome oxidase; energy metabolism; posterior cingulate cortex; Alzheimer's disease; brain mapping; gender Decrements in energy metabolism are one of the earliest detectable abnormalities in Alzheimer's disease (AD). Positron emission tomography (PET) studies on subjects homozygotic for the ⑀4 allele of the apolipoprotein E (APOE) gene, with no symptoms of AD, demonstrate metabolic reductions in posterior cingulate, parietal, temporal, and prefrontal cortices (Reiman et al., 1996;Small et al., 2000). Their largest decrement was in the posterior cingulate cortex (PCC) (Reiman et al., 1996), as in the case of AD (Minoshima et al., 1994). Another PET study (Minoshima et al., 1997) confirmed that although normal subjects show intense PCC metabolic activity, early-stage AD patients suffered a PCC decrement (21-22%) that was significantly greater than that seen in other cortical regions. This greater hypometabolism determined by PET is not merely an artifact of generalized atrophy (Ibanez et al., 1998) or AD histopathology that is lower in PCC than the other regions (Braak and Braak, 1998), although degeneration of PCC occurs in AD (Brun and Gustafson, 1976). Severity of AD symptoms is correlated with hypoactivity in PCC but not temporal regions, as measured with PE...

show abstract

Demonstration of decreased posterior cingulate perfusion in mild Alzheimer's disease by means of H2 15O positron emission tomography

Cited by 61 publications

References 8 publications

Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance

Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance

Animal model of posterior cingulate cortex hypometabolism implicated in amnestic MCI and AD

Energy Hypometabolism in Posterior Cingulate Cortex of Alzheimer's Patients: Superficial Laminar Cytochrome Oxidase Associated with Disease Duration

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