Positron Emission Tomography Scans Obtained for the Evaluation of Cognitive Dysfunction

David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Seminars in Nuclear Medicine (Impact Factor: 3.34). 08/2008; 38(4):251-61. DOI: 10.1053/j.semnuclmed.2008.02.006
Source: PubMed


The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism, with devastating neuropathologic, clinical, social, and economic consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are performed with (18)F-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility for clinicians evaluating patients with cognitive impairment and in distinguishing among primary neurodegenerative disorders and other etiologies contributing to cognitive decline. In addition to focusing on the effects on cerebral metabolism examined with (18)F-fluorodeoxyglucose PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact on the enormous human toll exacted by these diseases.

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Available from: Lisa Mosconi, Oct 09, 2015
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    • "Similarly, the IWG criteria for prodromal AD require the positivity of biomarkers, in association with the presence of hippocampal-type memory dysfunction (Dubois et al., 2014). [ 18 F]FDG-PET has been recognized as a crucial diagnostic marker in dementia since the early disease phases, predicting the possible progression to AD in MCI subjects (Anchisi et al., 2005; Chételat et al., 2005; Mosconi, 2005; Mosconi et al., 2008; Fouquet et al., 2009; Patterson II et al., 2010; Brück et al., 2013; Dukart et al., 2013; Hatashita & Yamasaki, 2013; Prestia et al., 2013), and allowing the exclusion of AD pathology (Silverman et al., 2008; Ossenkoppele et al., 2013). The typical AD metabolic pattern was shown even years before the disease onset, as proven in dominantly inherited AD (Bateman et al., 2012) and in familial sporadic cases (Mosconi et al., 2014). "
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    ABSTRACT: [(18)F]FDG-PET imaging has been recognized as a crucial diagnostic marker in Mild Cognitive Impairment (MCI), supporting the presence or the exclusion of Alzheimer's Disease (AD) pathology. A clinical heterogeneity, however, underlies MCI definition. In this study, we aimed to evaluate the predictive role of single-subject voxel-based maps of [(18)F]FDG distribution generated through statistical parametric mapping (SPM) in the progression to different dementia subtypes in a sample of 45 MCI. Their scans were compared to a large normal reference dataset developed and validated for comparison at single-subject level. Additionally, Aβ42 and Tau CSF values were available in 34 MCI subjects. Clinical follow-up (mean 28.5 ± 7.8 months) assessed subsequent progression to AD or non-AD dementias. The SPM analysis showed: 1) normal brain metabolism in 14 MCI cases, none of them progressing to dementia; 2) the typical temporo-parietal pattern suggestive for prodromal AD in 15 cases, 11 of them progressing to AD; 3) brain hypometabolism suggestive of frontotemporal lobar degeneration (FTLD) subtypes in 7 and dementia with Lewy bodies (DLB) in 2 subjects (all fulfilled FTLD or DLB clinical criteria at follow-up); and 4) 7 MCI cases showed a selective unilateral or bilateral temporo-medial hypometabolism without the typical AD pattern, and they all remained stable. In our sample, objective voxel-based analysis of [(18)F]FDG-PET scans showed high predictive prognostic value, by identifying either normal brain metabolism or hypometabolic patterns suggestive of different underlying pathologies, as confirmed by progression at follow-up. These data support the potential usefulness of this SPM [(18)F]FDG PET analysis in the early dementia diagnosis and for improving subject selection in clinical trials based on MCI definition.
    Clinical neuroimaging 01/2015; 7:187-94. DOI:10.1016/j.nicl.2014.12.004 · 2.53 Impact Factor
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    • "Although limited, there is evidence of an association between metabolic activity seen with FDG-PET imaging and increased neurofibrillary tangles, senile plaques, and neuronal loss in patients with verified AD [47]. PET determinations of glucose metabolism in AD show a consistent pattern of reduced glucose use beginning in posterior cingulate, parietal and temporal regions and spreading to the prefrontal cortices [48]. The extent of hypometabolism correlates with severity of cognitive impairment and often shows right/left hemispheric asymmetry at early stages of diseases [49]–[51]. "
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    ABSTRACT: The objective of this study was to examine the effects of estrogen-based hormone therapy (HT) on regional cerebral metabolism in postmenopausal women (mean age = 58, SD = 5) at risk for development of dementia. The prospective clinical trial design included pre- and post-intervention neuroimaging of women randomized to continue (HT+) or discontinue (HT-) therapy following an average of 10 years of use. The primary outcome measure was change in brain metabolism during the subsequent two years, as assessed with fluorodeoxyglucose-18 positron emission tomography (FDG-PET). Longitudinal FDG-PET data were available for 45 study completers. Results showed that women randomized to continue HT experienced relative preservation of frontal and parietal cortical metabolism, compared with women randomized to discontinue HT. Women who discontinued 17-β estradiol (17βE)-based HT, as well as women who continued conjugated equine estrogen (CEE)-based HT, exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical (PCC) area. Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins (with either 17βE or CEE). Together, these findings suggest that among postmenopausal subjects at risk for developing dementia, regional cerebral cortical metabolism is relatively preserved for at least two years in women randomized to continue HT, compared with women randomized to discontinue HT. In addition, continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC, known to undergo the most significant decline in the earliest stages of Alzheimer's disease. NCT00097058.
    PLoS ONE 03/2014; 9(3):e89095. DOI:10.1371/journal.pone.0089095 · 3.23 Impact Factor
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    • "Further, while probing reduction in glucose metabolism by [ 18 F]FDG PET in neurological conditions is of clinical interest [1] [2] [3] [4] [9] [10] [11] and compliments our internal interest to better Figure 5. Plot of the results of the Infinity model with the input-function derived from the VC, IDIF VC . Statistical significant decline in cerebral glucose metabolism was observed in the basal ganglia and olfactory bulb with a concomitant increase in the amygdala complex. "
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    ABSTRACT: Positron emission tomography (PET) imaging with the glucose analog 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F] FDG) has demonstrated clinical utility for the monitoring of brain glucose metabolism alteration in progressive neurodegenerative diseases. We examined dynamic [(18)F]FDG PET imaging and kinetic modeling of atlas-based regions to evaluate regional changes in the cerebral metabolic rate of glucose in the widely-used 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. Following a bolus injection of 18.5 ± 1 MBq [(18)F]FDG and a 60-minute PET scan, image-derived input functions from the vena cava and left ventricle were used with three models, including Patlak graphical analysis, to estimate the influx constant and the metabolic rate in ten brain regions. We observed statistically significant changes in [(18)F]FDG uptake ipsilateral to the 6-OHDA injection in the basal ganglia, olfactory bulb, and amygdala regions; and these changes are of biological relevance to the disease. These experiments provide further validation for the use of [(18)F]FDG PET imaging in this model for drug discovery and development.
    American Journal of Nuclear Medicine and Molecular Imaging 03/2013; 3(2):129-41. · 3.25 Impact Factor
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