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See detailMultivariate analysis of cognitive profiles in Alzheimer's disease
Bastin, Christine ULg; Leclercq, Yves ULg; Collette, Fabienne ULg et al

in Proceedings of the 8th bi-annual Meeting of the Belgian Society for Neuroscience (2009)

The neuropsychological profiles of patients with early Alzheimer’s disease (AD) appear to be heterogeneous. In this study, we examined whether this heterogeneity corresponds to the existence of ... [more ▼]

The neuropsychological profiles of patients with early Alzheimer’s disease (AD) appear to be heterogeneous. In this study, we examined whether this heterogeneity corresponds to the existence of cognitively distinct subtypes of AD or rather to impairments along a continuum of performances in different cognitive domains. A large group of 187 AD patients recruited in the European project NEST-DD performed a neuropsychological battery. A factor analysis of cognitive performance identified three factors, which respectively reflected attentional/instrumental function, declarative memory and executive function. Three clustering methods were applied on the factor scores in order to explore the existence of separate groups. The clustering methods indicated that cognitive profiles among the patients were sufficiently variable to identify clusters, but there was continuity between clusters rather than clear-cut subtypes. Moreover, clusters corresponded to various combinations of relatively impaired and preserved functions, suggesting multidimensional distribution within a large population of patients. Finally, clusters of cognitive profiles were characterized by different levels of metabolism in brain regions commonly (but variably) involved or relatively preserved in AD. [less ▲]

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See detailNeural correlates of anosognosia for cognitive impairment in Alzheimer's disease
Salmon, Eric ULg; Perani, D.; Herholz, K. et al

in Human Brain Mapping (2006), 27(7), 588-597

We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients ... [more ▼]

We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients' cognitive impairment by answering a structured questionnaire. Subjects rated 13 cognitive domains as not impaired or associated with mild, moderate, severe, or very severe difficulties, and a sum score was calculated. Two measures of anosognosia were derived. A patient's self assessment, unconfounded by objective measurements of cognitive deficits such as dementia severity and episodic memory impairment, provided an estimate of impaired self-evaluative judgment about cognition in AD. Impaired self-evaluation was related to a decrease in brain metabolism measured with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in orbital prefrontal cortex and in medial temporal structures. In a cognitive model of anosognosia, medial temporal dysfunction might impair a comparison mechanism between current information on cognition and personal knowledge. Hypoactivity in orbitofrontal cortex may not allow AD patients to update the qualitative judgment associated with their impaired cognitive abilities. Caregivers perceived greater cognitive impairments than patients did. The discrepancy score between caregiver's and patient's evaluations, an other measure of anosognosia, was negatively related to metabolic activity located in the temporoparietal junction, consistent with an impairment of self-referential processes and perspective taking in AD. [less ▲]

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See detailDiscrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET
Herholz, K.; Salmon, Eric ULg; Perani, D. et al

in Neuroimage (2002), 17(1), 302-316

A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal ... [more ▼]

A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis. (C) 2002 Elsevier Science (USA). [less ▲]

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