- Email: [email protected]
Reduced frontal oxygenation during a verbal fluency test in patients suffering from Alzheimer's disease
P268
Poster Presentations P2
Background: The presence of b-amyloid plaques in brain is a hallmark of Alzheimer’s disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Positron Emission Tomography (PET) radioligands that binds selectively to b-amyloid are promising new tools supporting the clinical diagnoses of AD. In addition, such methodology may be useful for evaluation of new drugs aiming at reduction of amyloid plaque load. Methods: We have utilized 1) in vitro binding to b-amyloid fibrils as well as cortical sections from human AD brain, 2) ex vivo binding data in aged tg2576 mice after i.v. administration and 3) PET studies in cynomolgus monkeys, to describe the properties of this new PET ligand. Results: Here we describe a new radioligand (AZD4694) with high affinity for b-amyloid fibrils in vitro (Kd 2.3 6 0.3 nM). In cortical sections from human AD brain [3H]AZD4694 selectively labelled b-amyloid deposits in gray matter with low level of non-specific binding to plaque devoid white matter. Ex vivo binding data in aged tg2576 mice after intravenous administration showed that [3H]AZD4694 selectively labelled b-amyloid plaques with a low levels of nonspecific binding. Congo red labelling in adjacent sections from the same individual showed that [3H]AZD4694 and congo red labeled apparently identical structures. The suitability of [18F]AZD4694 as a potential PET radioligand was demonstrated further in cynomolgus monkeys. [18F]AZD4694 rapidly entered the monkey brain with an exposure of about 5 % of the total injected dose. Brain uptake of [18F]AZD4694 peaked within two minutes after injection whereafter brain radioactivity rapidly cleared reaching a homogenous low level after 50 min. Conclusions: Taken together, the preclinical profile of AZD4694 suggests that fluorine-18 labelled AZD4694 may have potential for PET-visualization of b-amyloid deposits in the living human brain. P2-024
EXAMINATION OF DEFAULT MODE NETWORK ACTIVITY ALONG THE COGNITIVE CONTINUUM: NORMAL AGING, MCI AND AD
Mary M. Machulda, Ramesh Avula, Prashanthi Vemuri, Matthew L. Senjem, Scott Przybelski, Jeff Gunter, Heidi A. Edmonson, Brad Boeve, David Knopman, Ronald Petersen, Clifford R. Jack, Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: The Default Mode Network (DMN) is one of the cognitive networks that is metabolically active when subjects are not engaged in a specified cognitive task. Brain regions that constitute the DMN include the posterior cingulate, lateral parietal, and medial frontal cortex. Along with medial temporal lobe structures, some of these regions are also involved with episodic memory function. These same anatomic areas undergo preferential amyloid plaque formation in AD, and therefore the ability to detect alterations in this network has significant implications for understanding and detecting functional brain changes in these individuals. Methods: We scanned 16 cognitively normal elderly (CN), 16 amnestic MCI (aMCI), and 14 probable AD matched for age and education at 3T. Subjects were instructed to keep their eyes closed. Resting functional MR time-series were preprocessed using SPM5, which included slice timing correction, motion correction and normalization to the MNI_EPI template. Data were smoothed with an 8mm kernel. The preprocessed data were separated into independent components using FSL MELODIC. We used a template matching procedure to identify the DMN for each subject that was then entered into one- and two-sample t-tests. Results: The CN group showed activation in areas matching the DMN including a large region in the posterior cingulate, lateral inferior parietal lobe bilaterally, and medial frontal cortex. The aMCI group showed activation in these same regions. The AD group showed more diffuse activation that included the posterior cingulate, lateral inferior parietal lobe bilaterally, thalamus, and spotty areas in the dorsolateral prefrontal cortex. The CN vs. aMCI comparison revealed greater activation in the CN group, primarily in the posterior cingulate (t ¼ 2.77, p < .05, uncorrected; 22 voxels). The CN vs. AD comparison showed greater activation in the CN group in a substantially larger region encompassing the posterior cingulate (t ¼ 3.43, p < .05, uncorrected; 764 voxels) and the right lateral parietal lobe (t ¼ 3.11, p < .05, uncorrected, 43 voxels). Conclusions: Our results provide evidence for 1) disruption of DMN circuitry in the posterior cingulate in aMCI, and to a greater extent in AD, 2) potential of DMN changes as a biomarker for early detection of AD.
P2-025
SUBCORTICAL FIBER TRACT INTEGRITY AND THE CERAD COGNITIVE BATTERY IN PATIENTS WITH ALZHEIMER’S DISEASE: A MULTIVARIATE APPROACH TO DETECT MORPHOLOGICAL CORRELATES OF COGNITIVE FAILURE
Maximilian Wagner1, Thomas Meindl1, Gene Alexander2, Kristina Hennig-Fast1, Katharina Bu¨rger1, Jens Benninghoff1, Rolf Engel1, Maximilian F. Reiser1, Hans J. Mo¨ller1, Harald Hampel3, Stefan J. Teipel4, 1 Ludwig Maximilian University, Munich, Germany; 2Arizona State University, Phoenix, AZ, USA; 3Trinity College, University of Dublin, Dublin, Ireland; 4University of Rostock, Rostock, Germany. Contact e-mail: [email protected] Background: Dementia in Alzheimer’s disease (AD) is characterized by a specific pattern of cognitive changes that is believed to result from the loss of intracortical projecting fiber tracts and their synaptic contacts. Diffusion Tensor Imaging (DTI) determines the integrity of subcortical fiber tracts in vivo. Our aim was to discover white matter tracts whose functional disconnection causes decline in specific cognitive domains in AD. Methods: 21 patients fulfilling the NINCDS-ARDRA criteria for probable AD underwent DT-MRI at 3 Tesla. Cognitive functions were assessed using the neuropsychological CERAD battery. We employed a multivariate network analysis of fractional anisotropy maps to investigate the correlation between performance in CERAD subtest scores and fiber tract integrity throughout the cerebral white matter. Results: We found a significant spatial pattern of altered white matter microstructure underlying domain specific cognitive impairment in patients with AD. Word learning was correlated with white matter microstructure in the cingulate, the parahippocampal and fusiform gyrus and right lateral parietal, temporal and frontal regions. Word recall was associated with the bilateral cingulate and medial frontal gyrus and the right superior frontal and superior temporal gyrus. Word recognition was correlated with the cingulate gyrus bilaterally, the right cuneus and thalamus as well as the left superior longitudinal fascicle. Verbal fluency was associated with the cingulate gyrus, the medial frontal gyrus and the cuneus as well as left temporal and right frontal and parietal regions. Naming was correlated with FA in the anterior cingulate, the medial frontal, parahippocampal and lingual gyrus, the cuneus and the left parietal lobe. Constructional praxis depended on integrity of the uncus, the parahippocampal and lingual gyrus, the cuneus and lateral temporo-parietal regions. Conclusions: Our results suggest that fiber connections between several key regions are involved in cognitive decline in AD: First, an underlying cognitive network as basis for integrated cognitive function, possibly reflecting the default mode network whose deactivation precedes the performance of specific cognitive tasks; second, additional brain areas that are involved in specific cognitive functions. As a first study, our data may guide future research to determine the interaction between cognition and white matter connectivity. P2-026
REDUCED FRONTAL OXYGENATION DURING A VERBAL FLUENCY TEST IN PATIENTS SUFFERING FROM ALZHEIMER’S DISEASE
Julia B. M. Langer, Martin Schecklmann, Thomas T. Polak, Christine Leonhard, Thomas Leitner, Martina Rothenhoefer, Andreas J. Fallgatter, University Wu¨rzburg, Wu¨rzburg, Germany. Contact e-mail: [email protected]
Poster Presentations P2 Background: The technique of Near-Infrared Spectroscopy (NIRS) is a noninvasive optical method allowing the in vivo measurement of brain oxygenation by assessing changes in the concentration of oxy- [O2Hb] and deoxygenated [HHb] haemoglobin in the cerebral cortex. Recent studies show that controls display a typical activation pattern during a verbal fluency task (mainly involving prefrontal areas). We expected that patients suffering from Alzheimer’s disease display altered activation patterns that progress over time. Methods: 66 AD-patients and 68 age and gender matched healthy controls were measured during two versions of a verbal fluency task (VFT; letter and category using weekdays as a control task) using 44-channel NIRS. 8 patients and 16 controls completed a follow-up measurement after one year. Results: During both versions of the VFT AD-patients showed deficient activation over frontal areas as compared to healthy controls with more distinct differences in the letter version. The activation in frontal areas correlated positively with the behavioural performance during the VFT and also with the severity of AD as assessed with neuropsychological tests. After one year AD-patients showed decreased activation in five NIRS-channels covering the left dorsolateral prefrontal cortex, whereas controls showed no significant changes over the one-year interval. The activation changes in the deficient ‘‘frontal cluster’’ were correlated with the decrease of the MMSE score, with greater decrease indicating lower MMSE score at the follow-up. Conclusions: NIRS seems to be a well suited instrument to measure disease related changes in the cortex of AD patients and their progression over time. As alternations in oxygenation probably occur before atrophy in affected brain regions, NIRS could perhaps be used to develop methods for the early detection of AD. P2-027
NEURAL CORRELATES OF SEMANTIC PROCESSING IN OLDER ADULTS WITH COGNITIVE COMPLAINTS AND AMNESTIC MCI
Vanessa Taler1, Andrew J. Saykin1, John D. West1, Laura A , Flashman2, Heather A. Wishart2, Laura A. Rabin3, Nadia Pare2, Robert B. Santulli2, 1 Indiana University School of Medicine, Indianapolis, IN, USA; 2Dartmouth Medical School, Lebanon, NH, USA; 3City University of New York, New York, NY, USA. Contact e-mail: [email protected] Background: Lexical-semantic processing is impaired in Alzheimer’s disease (AD), likely due to to damage in frontal and temporal brain regions. However, less is known about how this processing is affected early in the disease course. We report a functional magnetic resonance imaging (fMRI) study of semantic processing in healthy control subjects (HCs), older adults with significant cognitive complaints (CCs), and patients with amnestic mild cognitive impairment (MCI). Methods: HC, CC and MCI subjects (n ¼ 30 per group, matched for age and education) were imaged using a GE Signa Scanner (1.5T). A semantic decision task was used in an event-related design. Subjects heard word pairs comprising a superordinate category (e.g., beverage) followed by a probe that was either an exemplar of the category (e.g., milk) or was not (e.g., carrot) and decided if the probe was a match (i.e., a category exemplar) or not. In a phonological control task, they decided if two pseudowords were identical or not. Results: No group differences were observed in overall accuracy or response time on the semantic task (p>0.3 in both cases). During the semantic vs. phonological contrast, signif-
P269
icantly increased BOLD activation was observed in the HC group relative to the MCI group in left inferior frontal gyrus (BA47; p<0.005). CC participants showed activations intermediate to HC and MCI participants (see Figure). Conclusions: BOLD response to an explicit semantic task appears to decline with increasing cognitive impairment in left inferior frontal gyrus, a region that previous research has implicated in explicit -rather than implicitsemantic processing. These results indicate that alterations in neural response during explicit lexical-semantic processing occur in very mild cognitive impairment, even in the absence of performance declines, and indicates a possible neural mechanism to account for deficits in explicit semantic processing in early-stage AD. P2-028
EFFECTS OF DONEPEZIL ON STRUCTURAL MRI AND CLINICAL MARKERS IN PATIENTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT: A RANDOMIZED, PLACEBO-CONTROLLED TRIAL
Bruno Dubois1,2, Marie Sarazin3, Ste´phane Lehericy4, Marie Chupin5, Isabelle Tonelli6, Line Garnero5, Didier Dormont5, 1Inserm U610 Unit, PARIS, France; 2Centre des Maladies Cognitives et Comportementales, Hopital de la Salpeˆtriere, Paris, France; 3Inserm U610 Unit, Paris, France; 4 Inserm U610 Unit and CENIR, Neuro-imaging Unit, Paris, France; 5 Cognitive Neuroscience and Brain Imaging Laboratory, CNRS UPR640, Paris, France; 6EISAI SAS, La Defense 2 Cedex, France. Contact e-mail: [email protected] Background: Several studies have demonstrated that the acetylcholinesterase inhibitor donepezil has a beneficial symptomatic impact on patients affected by Alzheimer’s disease (AD), not only on cognitive aspects, behaviors, but also on the global functioning and on the daily living activities, particularly in mild AD. The main objective of this study is to examine the effect of Donepezil on hippocampal volumes, a MRI marker of the disease progression, in a sample of patients with mild amnestic cognitive disorders evoking pre-demential stage of AD. Methods: In this double-blind, randomized, placebo-controlled, two-parallel groups study, the objective is to recruit 240 patients who will receive treatment with donepezil (10mg/d) or placebo for 52 weeks. To be eligible, all patients must meet all the following criteria: (1)an amnestic syndrome of temporal type measured by the Free and Cued Selective Reminding Test (free recall
PROTON SPECTROSCOPY AND NEUROPSYCHIATRIC SYNDROMES IN ALZHEIMER’S DISEASE AND COGNITIVE IMPAIRMENT NON-DEMENTIA: A COMMUNITYBASED STUDY
Lyssandra Santos Tascone, Dionı´sio Azevedo Jr, Mariana Tatsch, Cla´udio Campi Castro, Ca´ssio Machado Campos Bottino, University of Sa˜o Paulo, Sa˜o Paulo, Brazil. Contact e-mail: [email protected]
Fig. 1. HCs > MCIs (p ¼ 0.005); bar graph shows activation in HCs, CCs and MCIs in LIFG (x¼34, y¼82, z¼10).
Background: The pathophysiology and the neurobiology of the neuropsychiatric symptoms in Alzheimer’s disease (AD) are far from understood. The aim of the study was to describe the findings of proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer’s disease and cognitive
Poster Presentations P2
Background: The presence of b-amyloid plaques in brain is a hallmark of Alzheimer’s disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Positron Emission Tomography (PET) radioligands that binds selectively to b-amyloid are promising new tools supporting the clinical diagnoses of AD. In addition, such methodology may be useful for evaluation of new drugs aiming at reduction of amyloid plaque load. Methods: We have utilized 1) in vitro binding to b-amyloid fibrils as well as cortical sections from human AD brain, 2) ex vivo binding data in aged tg2576 mice after i.v. administration and 3) PET studies in cynomolgus monkeys, to describe the properties of this new PET ligand. Results: Here we describe a new radioligand (AZD4694) with high affinity for b-amyloid fibrils in vitro (Kd 2.3 6 0.3 nM). In cortical sections from human AD brain [3H]AZD4694 selectively labelled b-amyloid deposits in gray matter with low level of non-specific binding to plaque devoid white matter. Ex vivo binding data in aged tg2576 mice after intravenous administration showed that [3H]AZD4694 selectively labelled b-amyloid plaques with a low levels of nonspecific binding. Congo red labelling in adjacent sections from the same individual showed that [3H]AZD4694 and congo red labeled apparently identical structures. The suitability of [18F]AZD4694 as a potential PET radioligand was demonstrated further in cynomolgus monkeys. [18F]AZD4694 rapidly entered the monkey brain with an exposure of about 5 % of the total injected dose. Brain uptake of [18F]AZD4694 peaked within two minutes after injection whereafter brain radioactivity rapidly cleared reaching a homogenous low level after 50 min. Conclusions: Taken together, the preclinical profile of AZD4694 suggests that fluorine-18 labelled AZD4694 may have potential for PET-visualization of b-amyloid deposits in the living human brain. P2-024
EXAMINATION OF DEFAULT MODE NETWORK ACTIVITY ALONG THE COGNITIVE CONTINUUM: NORMAL AGING, MCI AND AD
Mary M. Machulda, Ramesh Avula, Prashanthi Vemuri, Matthew L. Senjem, Scott Przybelski, Jeff Gunter, Heidi A. Edmonson, Brad Boeve, David Knopman, Ronald Petersen, Clifford R. Jack, Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: The Default Mode Network (DMN) is one of the cognitive networks that is metabolically active when subjects are not engaged in a specified cognitive task. Brain regions that constitute the DMN include the posterior cingulate, lateral parietal, and medial frontal cortex. Along with medial temporal lobe structures, some of these regions are also involved with episodic memory function. These same anatomic areas undergo preferential amyloid plaque formation in AD, and therefore the ability to detect alterations in this network has significant implications for understanding and detecting functional brain changes in these individuals. Methods: We scanned 16 cognitively normal elderly (CN), 16 amnestic MCI (aMCI), and 14 probable AD matched for age and education at 3T. Subjects were instructed to keep their eyes closed. Resting functional MR time-series were preprocessed using SPM5, which included slice timing correction, motion correction and normalization to the MNI_EPI template. Data were smoothed with an 8mm kernel. The preprocessed data were separated into independent components using FSL MELODIC. We used a template matching procedure to identify the DMN for each subject that was then entered into one- and two-sample t-tests. Results: The CN group showed activation in areas matching the DMN including a large region in the posterior cingulate, lateral inferior parietal lobe bilaterally, and medial frontal cortex. The aMCI group showed activation in these same regions. The AD group showed more diffuse activation that included the posterior cingulate, lateral inferior parietal lobe bilaterally, thalamus, and spotty areas in the dorsolateral prefrontal cortex. The CN vs. aMCI comparison revealed greater activation in the CN group, primarily in the posterior cingulate (t ¼ 2.77, p < .05, uncorrected; 22 voxels). The CN vs. AD comparison showed greater activation in the CN group in a substantially larger region encompassing the posterior cingulate (t ¼ 3.43, p < .05, uncorrected; 764 voxels) and the right lateral parietal lobe (t ¼ 3.11, p < .05, uncorrected, 43 voxels). Conclusions: Our results provide evidence for 1) disruption of DMN circuitry in the posterior cingulate in aMCI, and to a greater extent in AD, 2) potential of DMN changes as a biomarker for early detection of AD.
P2-025
SUBCORTICAL FIBER TRACT INTEGRITY AND THE CERAD COGNITIVE BATTERY IN PATIENTS WITH ALZHEIMER’S DISEASE: A MULTIVARIATE APPROACH TO DETECT MORPHOLOGICAL CORRELATES OF COGNITIVE FAILURE
Maximilian Wagner1, Thomas Meindl1, Gene Alexander2, Kristina Hennig-Fast1, Katharina Bu¨rger1, Jens Benninghoff1, Rolf Engel1, Maximilian F. Reiser1, Hans J. Mo¨ller1, Harald Hampel3, Stefan J. Teipel4, 1 Ludwig Maximilian University, Munich, Germany; 2Arizona State University, Phoenix, AZ, USA; 3Trinity College, University of Dublin, Dublin, Ireland; 4University of Rostock, Rostock, Germany. Contact e-mail: [email protected] Background: Dementia in Alzheimer’s disease (AD) is characterized by a specific pattern of cognitive changes that is believed to result from the loss of intracortical projecting fiber tracts and their synaptic contacts. Diffusion Tensor Imaging (DTI) determines the integrity of subcortical fiber tracts in vivo. Our aim was to discover white matter tracts whose functional disconnection causes decline in specific cognitive domains in AD. Methods: 21 patients fulfilling the NINCDS-ARDRA criteria for probable AD underwent DT-MRI at 3 Tesla. Cognitive functions were assessed using the neuropsychological CERAD battery. We employed a multivariate network analysis of fractional anisotropy maps to investigate the correlation between performance in CERAD subtest scores and fiber tract integrity throughout the cerebral white matter. Results: We found a significant spatial pattern of altered white matter microstructure underlying domain specific cognitive impairment in patients with AD. Word learning was correlated with white matter microstructure in the cingulate, the parahippocampal and fusiform gyrus and right lateral parietal, temporal and frontal regions. Word recall was associated with the bilateral cingulate and medial frontal gyrus and the right superior frontal and superior temporal gyrus. Word recognition was correlated with the cingulate gyrus bilaterally, the right cuneus and thalamus as well as the left superior longitudinal fascicle. Verbal fluency was associated with the cingulate gyrus, the medial frontal gyrus and the cuneus as well as left temporal and right frontal and parietal regions. Naming was correlated with FA in the anterior cingulate, the medial frontal, parahippocampal and lingual gyrus, the cuneus and the left parietal lobe. Constructional praxis depended on integrity of the uncus, the parahippocampal and lingual gyrus, the cuneus and lateral temporo-parietal regions. Conclusions: Our results suggest that fiber connections between several key regions are involved in cognitive decline in AD: First, an underlying cognitive network as basis for integrated cognitive function, possibly reflecting the default mode network whose deactivation precedes the performance of specific cognitive tasks; second, additional brain areas that are involved in specific cognitive functions. As a first study, our data may guide future research to determine the interaction between cognition and white matter connectivity. P2-026
REDUCED FRONTAL OXYGENATION DURING A VERBAL FLUENCY TEST IN PATIENTS SUFFERING FROM ALZHEIMER’S DISEASE
Julia B. M. Langer, Martin Schecklmann, Thomas T. Polak, Christine Leonhard, Thomas Leitner, Martina Rothenhoefer, Andreas J. Fallgatter, University Wu¨rzburg, Wu¨rzburg, Germany. Contact e-mail: [email protected]
Poster Presentations P2 Background: The technique of Near-Infrared Spectroscopy (NIRS) is a noninvasive optical method allowing the in vivo measurement of brain oxygenation by assessing changes in the concentration of oxy- [O2Hb] and deoxygenated [HHb] haemoglobin in the cerebral cortex. Recent studies show that controls display a typical activation pattern during a verbal fluency task (mainly involving prefrontal areas). We expected that patients suffering from Alzheimer’s disease display altered activation patterns that progress over time. Methods: 66 AD-patients and 68 age and gender matched healthy controls were measured during two versions of a verbal fluency task (VFT; letter and category using weekdays as a control task) using 44-channel NIRS. 8 patients and 16 controls completed a follow-up measurement after one year. Results: During both versions of the VFT AD-patients showed deficient activation over frontal areas as compared to healthy controls with more distinct differences in the letter version. The activation in frontal areas correlated positively with the behavioural performance during the VFT and also with the severity of AD as assessed with neuropsychological tests. After one year AD-patients showed decreased activation in five NIRS-channels covering the left dorsolateral prefrontal cortex, whereas controls showed no significant changes over the one-year interval. The activation changes in the deficient ‘‘frontal cluster’’ were correlated with the decrease of the MMSE score, with greater decrease indicating lower MMSE score at the follow-up. Conclusions: NIRS seems to be a well suited instrument to measure disease related changes in the cortex of AD patients and their progression over time. As alternations in oxygenation probably occur before atrophy in affected brain regions, NIRS could perhaps be used to develop methods for the early detection of AD. P2-027
NEURAL CORRELATES OF SEMANTIC PROCESSING IN OLDER ADULTS WITH COGNITIVE COMPLAINTS AND AMNESTIC MCI
Vanessa Taler1, Andrew J. Saykin1, John D. West1, Laura A , Flashman2, Heather A. Wishart2, Laura A. Rabin3, Nadia Pare2, Robert B. Santulli2, 1 Indiana University School of Medicine, Indianapolis, IN, USA; 2Dartmouth Medical School, Lebanon, NH, USA; 3City University of New York, New York, NY, USA. Contact e-mail: [email protected] Background: Lexical-semantic processing is impaired in Alzheimer’s disease (AD), likely due to to damage in frontal and temporal brain regions. However, less is known about how this processing is affected early in the disease course. We report a functional magnetic resonance imaging (fMRI) study of semantic processing in healthy control subjects (HCs), older adults with significant cognitive complaints (CCs), and patients with amnestic mild cognitive impairment (MCI). Methods: HC, CC and MCI subjects (n ¼ 30 per group, matched for age and education) were imaged using a GE Signa Scanner (1.5T). A semantic decision task was used in an event-related design. Subjects heard word pairs comprising a superordinate category (e.g., beverage) followed by a probe that was either an exemplar of the category (e.g., milk) or was not (e.g., carrot) and decided if the probe was a match (i.e., a category exemplar) or not. In a phonological control task, they decided if two pseudowords were identical or not. Results: No group differences were observed in overall accuracy or response time on the semantic task (p>0.3 in both cases). During the semantic vs. phonological contrast, signif-
P269
icantly increased BOLD activation was observed in the HC group relative to the MCI group in left inferior frontal gyrus (BA47; p<0.005). CC participants showed activations intermediate to HC and MCI participants (see Figure). Conclusions: BOLD response to an explicit semantic task appears to decline with increasing cognitive impairment in left inferior frontal gyrus, a region that previous research has implicated in explicit -rather than implicitsemantic processing. These results indicate that alterations in neural response during explicit lexical-semantic processing occur in very mild cognitive impairment, even in the absence of performance declines, and indicates a possible neural mechanism to account for deficits in explicit semantic processing in early-stage AD. P2-028
EFFECTS OF DONEPEZIL ON STRUCTURAL MRI AND CLINICAL MARKERS IN PATIENTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT: A RANDOMIZED, PLACEBO-CONTROLLED TRIAL
Bruno Dubois1,2, Marie Sarazin3, Ste´phane Lehericy4, Marie Chupin5, Isabelle Tonelli6, Line Garnero5, Didier Dormont5, 1Inserm U610 Unit, PARIS, France; 2Centre des Maladies Cognitives et Comportementales, Hopital de la Salpeˆtriere, Paris, France; 3Inserm U610 Unit, Paris, France; 4 Inserm U610 Unit and CENIR, Neuro-imaging Unit, Paris, France; 5 Cognitive Neuroscience and Brain Imaging Laboratory, CNRS UPR640, Paris, France; 6EISAI SAS, La Defense 2 Cedex, France. Contact e-mail: [email protected] Background: Several studies have demonstrated that the acetylcholinesterase inhibitor donepezil has a beneficial symptomatic impact on patients affected by Alzheimer’s disease (AD), not only on cognitive aspects, behaviors, but also on the global functioning and on the daily living activities, particularly in mild AD. The main objective of this study is to examine the effect of Donepezil on hippocampal volumes, a MRI marker of the disease progression, in a sample of patients with mild amnestic cognitive disorders evoking pre-demential stage of AD. Methods: In this double-blind, randomized, placebo-controlled, two-parallel groups study, the objective is to recruit 240 patients who will receive treatment with donepezil (10mg/d) or placebo for 52 weeks. To be eligible, all patients must meet all the following criteria: (1)an amnestic syndrome of temporal type measured by the Free and Cued Selective Reminding Test (free recall
PROTON SPECTROSCOPY AND NEUROPSYCHIATRIC SYNDROMES IN ALZHEIMER’S DISEASE AND COGNITIVE IMPAIRMENT NON-DEMENTIA: A COMMUNITYBASED STUDY
Lyssandra Santos Tascone, Dionı´sio Azevedo Jr, Mariana Tatsch, Cla´udio Campi Castro, Ca´ssio Machado Campos Bottino, University of Sa˜o Paulo, Sa˜o Paulo, Brazil. Contact e-mail: [email protected]
Fig. 1. HCs > MCIs (p ¼ 0.005); bar graph shows activation in HCs, CCs and MCIs in LIFG (x¼34, y¼82, z¼10).
Background: The pathophysiology and the neurobiology of the neuropsychiatric symptoms in Alzheimer’s disease (AD) are far from understood. The aim of the study was to describe the findings of proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer’s disease and cognitive