Longitudinal brain metabolic changes from amnestic Mild Cognitive Impairment to Alzheimer's disease
ABSTRACT A sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential monitoring marker, in patients with amnestic mild cognitive impairment, according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen amnestic mild cognitive impairment patients underwent magnetic resonance imaging and 18FDG-positron emission tomography scans both at inclusion and 18 months later. Baseline and follow-up positron emission tomography data were corrected for partial volume effects and spatially normalized using magnetic resonance imaging data, scaled to the vermis and compared using SPM2. 'PET-PAC' maps reflecting metabolic per cent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than non-converters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-positron emission tomography for monitoring early Alzheimer's disease progression.
- SourceAvailable from: Chiara Cerami
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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). "
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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- "A popular method to analyze LNI data, e.g. (Fotenos et al., 2005; Fouquet et al., 2009; Frings et al., 2011; Hedman et al., 2011; Hua et al., 2009, 2010; Jack et al., 2009; Josephs et al., 2008; Kalkers et al., 2002; Kasai et al., 2003; Martensson et al., 2012; Paviour et al., 2006; Rosas et al., 2011; Sabuncu et al., 2011; Sluimer et al., 2008; Wenger et al., 2011; Whitwell et al., 2007; Wilde et al., 2012), employs subject-level summary measures (e.g. the annualized difference between two time-points, the slope of a regression line, or metrics from longitudinal deformation fields), which are computed from the sequence of repeated measures for each individual. Standard parametric or non-parametric statistical methods can then be utilized to perform a cross-subject analysis of these summary measures. "
ABSTRACT: We present an extension of the Linear Mixed Effects (LME) modeling approach to be applied to the mass-univariate analysis of longitudinal neuroimaging (LNI) data. The proposed method, called spatiotemporal LME or ST-LME, builds on the flexible LME framework and exploits the spatial structure in image data. We instantiated ST-LME for the analysis of cortical surface measurements (e.g. thickness) computed by FreeSurfer, a widely-used brain Magnetic Resonance Image (MRI) analysis software package. We validate the proposed ST-LME method and provide a quantitative and objective empirical comparison with two popular alternative methods, using two brain MRI datasets obtained from the Alzheimer's disease neuroimaging initiative (ADNI) and Open Access Series of Imaging Studies (OASIS). Our experiments revealed that ST-LME offers a dramatic gain in statistical power and repeatability of findings, while providing good control of the false positive rate.NeuroImage 05/2013; 81. DOI:10.1016/j.neuroimage.2013.05.049 · 6.36 Impact Factor
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- "Retrograde amnesia for personal events might arise from a synchronization abnormality during retrieval between processing of affectively laden personal events (that is assumed to preferentially and preponderantly engage the right hemisphere) and fact-based processing (that is considered to preferentially and preponderantly engage the left hemisphere; Fink et al., 1996; Markowitsch et al., 2000b). It might be due to a neurological event that leads to damage of right fronto-temporal connections (such as the right uncinate fascicle; Levine et al., 1998, 2009; LaBar and Cabeza, 2006; Fouquet et al., 2009) or a psychological stressinduced right fronto-temporal disconnectivity (Reinhold et al., 2006; Reinhold and Markowitsch, 2007, 2009; Brand et al., 2009). "
ABSTRACT: Remembering the past is a core feature of human beings, enabling them to maintain a sense of wholeness and identity and preparing them for the demands of the future. Forgetting operates in a dynamic neural connection with remembering, allowing the elimination of unnecessary or irrelevant information overload and decreasing interference. Stress and traumatic experiences could affect this connection, resulting in memory disturbances, such as functional amnesia. An overview of clinical, epidemiological, neuropsychological, and neurobiological aspects of functional amnesia is presented, by preponderantly resorting to own data from patients with functional amnesia. Patients were investigated medically, neuropsychologically, and neuroradiologically. A detailed report of a new case is included to illustrate the challenges posed by making an accurate differential diagnosis of functional amnesia, a condition that may encroach on the boundaries between psychiatry and neurology. Several mechanisms may play a role in "forgetting" in functional amnesia, such as retrieval impairments, consolidating defects, motivated forgetting, deficits in binding and reassembling details of the past, deficits in establishing a first person autonoetic connection with personal events, and loss of information. In a substantial number of patients, we observed a synchronization abnormality between a frontal lobe system, important for autonoetic consciousness, and a temporo-amygdalar system, important for evaluation and emotions, which provides empirical support for an underlying mechanism of dissociation (a failure of integration between cognition and emotion). This observation suggests a mnestic blockade in functional amnesia that is triggered by psychological or environmental stress and is underpinned by a stress hormone mediated synchronization abnormality during retrieval between processing of affect-laden events and fact-processing.Frontiers in Psychology 11/2012; 3:403. DOI:10.3389/fpsyg.2012.00403 · 2.80 Impact Factor