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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    • "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.
    Journal of Alzheimer's disease: JAD 05/2015; 47(4):965-975. DOI:10.3233/JAD-142643 · 4.15 Impact Factor
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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. "

    Dementia 05/2015; 14(3):285-97. DOI:10.1177/1471301214562135 · 0.91 Impact Factor
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    • "Given that the pathogenic constituent of cerebral amyloid plaques are the Aβ 40 and Aβ 42 isoforms, it is not surprising to find enhanced Aβ levels in the brain of MCI subjects. The latter has been extensively corroborated with [(11)C]Pittsburgh Compound B (PiB)-positron emission tomography (PET) scans, showing that patterns of PiB retention in MCI largely resemble that observed in AD patients (Forsberg et al., 2008; Kemppainen et al., 2007). Furthermore, PiB levels in the temporal cortex have demonstrated accounting for episodic memory deficits in MCI subjects (Chetelat et al., 2011). "
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    ABSTRACT: Evidence suggests that amyloid-beta (Aβ) deposition parallels sleep deficits in Alzheimer's disease (AD). However, it remains unknown whether impaired sleep and changes in plasma Aβ levels are related in amnestic mild cognitive impairment (aMCI) subjects, and whether both markers are further associated with cortical thinning in canonical AD regions. To jointly address this issue, we investigated relationships between changes in physiological sleep and plasma Aβ concentrations in 21 healthy old (HO) adults and 21 aMCI subjects, and further assessed whether these two factors were associated with cortical loss in each group. aMCI, but not HO subjects, showed significant relationships between disrupted slow-wave sleep (SWS) and increased plasma levels of Aβ42. We also found that shortened rapid-eye movement (REM) sleep in aMCI correlated with thinning of the posterior cingulate, precuneus, and postcentral gyrus; whereas higher levels of Aβ40 and Aβ42 accounted for grey matter (GM) loss of posterior cingulate and entorhinal cortex, respectively. These results support preliminary relationships between Aβ burden and altered sleep physiology observed in animal models of AD amyloidosis, and provide precise cortical correlates of these changes in older adults with aMCI. Taken together, these findings open new research avenues on the combined role of sleep, peripheral Aβ levels and cortical integrity in tracking the progression from normal aging to early neurodegeneration.
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