PET amyloid ligand [C-11]PIB uptake is increased in mild cognitive impairment

Turku PET Centre, University of Turku, Turku, Finland.
Neurology (Impact Factor: 8.29). 06/2007; 68(19):1603-6. DOI: 10.1212/01.wnl.0000260969.94695.56
Source: PubMed


Patients with mild cognitive impairment (MCI) have increased risk to develop Alzheimer disease (AD). In AD increased brain amyloid burden has been demonstrated in vivo with PET using N-methyl-[(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([(11)C]PIB) as a tracer.
To investigate whether patients with amnestic MCI would show increased [(11)C]PIB uptake, indicating early AD process.
We studied 13 patients with amnestic MCI and 14 control subjects with PET using [(11)C]PIB as tracer. Parametric images were computed by calculating the region-to-cerebellum ratio in each voxel over 60 to 90 minutes. Group differences in [(11)C]PIB uptake were analyzed with statistical parametric mapping (SPM) and automated region-of-interest (ROI) analysis.
The SPM analysis showed that patients with MCI had significantly higher [(11)C]PIB uptake vs control subjects in the frontal, parietal, and lateral temporal cortices as well as in the posterior cingulate showing the most prominent differences. These results were supported by the automated ROI analysis in which MCI patients showed in comparison with healthy control subjects increased [(11)C]PIB uptake in the frontal cortex (39% increase from the control mean, p < 0.01), the posterior cingulate (39%, p < 0.01), the parietal (31%, p < 0.01) and lateral temporal (28%, p < 0.001) cortices, putamen (17%, p < 0.05), and caudate (25%, p < 0.05). Individually, in the frontal cortex and posterior cingulate, 8 of 13 patients with MCI had [(11)C]PIB uptake values above 2 SD from the control mean. MCI subjects having at least one APOE epsilon4 allele tended to have higher [(11)C]PIB uptake than MCI subjects without APOE epsilon4.
At group level the elevated N-methyl-[(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([(11)C]PIB) uptake in patients with mild cognitive impairment (MCI) resembled that seen in Alzheimer disease (AD). At the individual level, about half of the MCI patients had [(11)C]PIB uptake in the AD range, suggestive of early AD process.

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    • "Tel.: +358 2 313 1866; Fax: +358 2 231 8191; E-mail: patients already have widespread Alzheimer-type brain amyloid burden and decreased brain metabolism, particularly in the parietal and temporal lobes, which are detected as an increased [ 11 C] Pittsburgh compound B (PIB) uptake and a decreased [ 18 F] fludeoxyglucose (FDG) uptake in positron emission tomography (PET) imaging [3] [4] [5]. Follow-up studies indicate an increasing [ 11 C]PIB uptake and a decreasing [ 18 F]FDG uptake during the phase of mild cognitive impairment (MCI) [6] [7], but the long-term interrelationship between these two biomarkers, i.e., between the distribution "
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    ABSTRACT: The aim of this longitudinal positron emission tomography (PET) study was to evaluate the interrelationship between brain metabolism and amyloid accumulation during the disease process from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Nine MCI patients, who converted to AD between two and five years, and nine healthy subjects underwent [11C]PIB and [18F]FDG PET scans at baseline and at 5 years. [11C]PIB uptake was clearly higher in MCI patients at baseline compared to controls and spread extensively to the cerebral cortex during the conversion to AD. [18F]FDG uptake was reduced especially in the temporal-parietal regions in MCI compared to controls at baseline, and widely over the cortex at the 5-year follow-up. The reduction in metabolism during the follow-up was significant in the posterior brain regions. In addition, brain amyloid load was positively associated with metabolism in posterior brain regions in MCI, but not after conversion to AD. The results suggest that there are interactions between brain amyloid accumulation and metabolism during the AD process, including a possible compensatory upregulation of posterior brain metabolism in the early phase.
    No preview · Article · Sep 2015 · Journal of Alzheimer's disease: JAD
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    • "In contrast to the tau-based NFTs, which begin to accumulate in the mesial temporal region, A␤ deposition begins in basal isocortex before spreading inwards to mesial temporal regions and finally involving more diffuse isocortical regions [11]. A number of in vivo imaging studies of A␤ have revealed deposition to be a diffuse neocortical pathology , with greatest binding in anterior neocortex and relatively little uptake in mesial temporal structures [12] [13] [14] [15]. Given the neocortical predominance of A␤ deposition , particularly in anterior regions, it is of note that clinical syndrome is not dominated by neurocognitive signs considered typical of these regions (e.g., primary executive impairments). "
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    ABSTRACT: Alzheimer’s disease (AD) is characterized by two primary pathologies: tau-related neurofibrillary tangles and the extracellular accumulation of amyloid-β (Aβ). The development of these pathologies is topologically distinct early in the disease, with Aβ beginning to accumulate as a diffuse, neocortical pathology, while tau-related pathology begins to form in mesial temporal regions. This study investigated the hypothesis that, by virtue of this distinction, there exist preferential associations between the primary pathologies and aspects of the cognitive phenotype. We investigated the relationship between cerebrospinal fluid (CSF) biomarkers for tau and Aβ pathologies with neurocognitive measures in 191 patients with mild cognitive impairment (MCI). Participants completed cognitive tests of new learning, information processing speed, and working memory. Separate regression models were computed and then followed up with mediation analyses to examine the predictive status of CSF biomarkers. The effect of Aβ on learning was mediated by phospho-tau (p = 0.008). In contrast, Aβ had a direct effect on information processing speed that was not mediated by phospho-tau (p = 0.59). No predictors were significant for working memory. This study provided evidence for a differential relationship of Aβ and phospho-tau pathologies on the neurocognitive phenotype of MCI. This supports the proposition that these primary AD pathologies maximally affect different aspects of cognition, and has potential implications for cognitive assessments and the use of biomarkers in disease-modifying therapeutic trials.
    Full-text · Article · May 2015 · Journal of Alzheimer's disease: JAD
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    • "see Andreasen et al., 1999; Petersen et al., 2010; Visser et al., 2009) and PiB-PET measures of amyloid deposition in the brain (e.g. see Forsberg et al., 2008; Jack et al., 2008; Kemppainen et al., 2007). In addition, these different types of biomarkers have also been shown to predict the development of dementia in individuals with MCI (e.g. "

    Preview · Article · May 2015 · Dementia
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