Functional imaging of cognition in Alzheimer's disease using positron emission tomography

Cyclotron Research Centre, University of Liège, B30 Sart Tilman, 4000 Liège, Belgium.
Neuropsychologia (Impact Factor: 3.3). 02/2008; 46(6):1613-23. DOI: 10.1016/j.neuropsychologia.2007.11.022
Source: PubMed


Positron emission tomography in Alzheimer's disease (AD) demonstrates a metabolic decrease, predominantly in associative posterior cortices (comprising the posterior cingulate cortex), and also involving medial temporal structures and frontal regions at a lesser degree. The level of activity in this wide network is roughly correlated with dementia severity, but several confounds (such as age, education or subcortical ischemic lesions) may influence the brain-behaviour relationship. Univariate analyses allow one to segregate brain regions that are particularly closely related to specific neuropsychological performances. For example, a relationship was established between the activity in lateral associative cortices and semantic performance in AD. The role of semantic capacities (subserved by temporal or parietal regions) in episodic memory tasks was also emphasized. The residual activity in medial temporal structures was related to episodic memory abilities, as measured by free recall performance, cued recall ability and recognition accuracy. More generally, AD patients' performance on episodic memory tasks was correlated with the metabolism in several structures of Papez's circuit (including the medial temporal and posterior cingulate regions). Multivariate analyses should provide complementary information on impaired metabolic covariance in functional networks of brain regions and the consequences for AD patients' cognitive performance. More longitudinal studies are being conducted that should tell us more about the prognostic value of initial metabolic impairment and the neural correlates of progressive deterioration of cognitive performance in AD.

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    • "This loss of episodic memory in AD has been interpreted in relation to the characteristic pattern of atrophy beginning in the entorhinal cortex and progressing across the hippocampus to the neocortex [Braak and Braak, 1991], as well as the involvement of more posterior structures including the posterior cingulate cortex [Nestor et al., 2006]. Task-related fMRI studies have confirmed that the hippocampus is connected functionally to posteromedial regions including the posterior cingulate cortex, precuneus, and lateral parietal regions [Greicius et al., 2004; Kahn et al., 2008; Salmon et al., 2008]. Accordingly, successful episodic memory performance requires coordinated and reciprocal activity between hippocampal/MTL and retrosplenial-parietal structures [Wagner et al., 2005; Miller et al., 2008; Sperling et al., 2010]. "
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    ABSTRACT: Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel-based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age- and education-matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole-brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each dementia syndrome. Hum Brain Mapp, 2013. © 201 Wiley Periodicals, Inc.
    No preview · Article · Apr 2014 · Human Brain Mapping
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    • "Brain metabolic activity at rest was measured by the 18F fluorodeoxyglucose method and positron emission tomography (FDG-PET). We adopted the cognitive-metabolic approach which has been widely used to reveal the cerebral dysfunction that underlies memory impairments in Alzheimer " s disease and MCI by pointing to regions whose metabolic activity is related to the variability of memory performance among patients (Salmon et al., 2008). The specific cerebral regions whose dysfunction subserves the impairment in episodic ABM in aMCI were identified by correlations between regional (voxel-based) metabolic activity and a fine-grained measure of the extent to which memories contained episodic information (the proportion of internal/episodic details contained in the memories). "
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    ABSTRACT: Autobiographical memory in amnestic Mild Cognitive Impairment (aMCI) is characterized by impaired retrieval of episodic memories, but relatively preserved personal semantic knowledge. This study aimed to identify (via FDG-PET) the neural substrates of impaired episodic specificity of autobiographical memories in 35 aMCI patients compared with 24 healthy elderly controls. Significant correlations between regional cerebral activity and the proportion of episodic details in autobiographical memories from two life periods were found in specific regions of an autobiographical brain network. In aMCI patients, more than in controls, specifically episodic memories from early adulthood were associated with metabolic activity in the cuneus and in parietal regions. We hypothesized that variable retrieval of episodic autobiographical memories in our aMCI patients would be related to their variable capacity to reactivate specific sensory-perceptual and contextual details of early adulthood events linked to reduced (occipito-parietal) visual imagery and less efficient (parietal) attentional processes. For recent memories (last year), a correlation emerged between the proportion of episodic details and activity in lateral temporal regions and the temporo-parietal junction. Accordingly, variable episodic memory for recent events may be related to the efficiency of controlled search through general events likely to provide cues for the retrieval of episodic details and to the ability to establish a self perspective favouring recollection. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Full-text · Article · Aug 2013 · Human Brain Mapping
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    • "Hence, the hippocampal region is regarded as one of the earliest cerebral structure affected by the pathological process (Braak and Braak, 1991) and its atrophy is part of the diagnosis biomarker support (McKhann et al., 2011). As pointed out by cognitivo-metabolic correlation studies (Desgranges et al., 1998; for review, see Salmon et al., 2008), the functional disturbance of this limbic structure is highly linked to the patients' episodic memory deficit. This approach has also highlighted other regions responsible for episodic memory deficits in the earlier stages of the disease, such as the posterior cingulate cortex (Chételat et al., 2003). "
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    ABSTRACT: The aim of the present study was to explore the cerebral substrates of episodic memory disorders in Alzheimer’s disease (AD) and investigate patients’ hyperactivations frequently reported in the functional imaging literature. It remains unclear whether some of these hyperactivations reflect real increased activity or deactivation disturbances in the default mode network (DMN). Using positron emission tomography (15O-H2O), cerebral blood flow was measured in 11 AD patients and 12 healthy elderly controls at rest and during encoding and stem-cued recall of verbal items. Subtractions analyses between the target and control conditions were performed and compared between groups. The average signal was extracted in regions showing hyperactivation in AD patients versus controls in both contrasts. To determine whether hyperactivations occurred in regions that were activated or deactivated during the memory tasks, we compared signal intensities between the target conditions versus rest. Our results showed reduced activation in AD patients compared to controls in several core episodic memory regions, including the medial temporal structures, during both encoding and retrieval. Patients also showed hyperactivations compared to controls in a set of brain areas. Further analyses conducted on the signal extracted in these areas indicated that most of these hyperactivations actually reflected a failure of deactivation. Indeed, whereas almost all of these regions were significantly more activated at rest than during the target conditions in controls, only one region presented a similar pattern of deactivation in patients. Altogether, our findings suggest that hyperactivations in AD must be interpreted with caution and may not systematically reflect increased activity. Although there has been evidence supporting the existence of genuine compensatory mechanisms, dysfunction within the DMN may be responsible for part of the apparent hyperactivations reported in the literature on AD.
    Full-text · Article · May 2012 · Frontiers in Human Neuroscience
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