- Email: [email protected]
The NIH toolbox for assessment of neurological and behavioral function
P218
Poster Presentations P1
study not only the microstructure of the white matter brain but also that of the grey matter. Indeed, higher sensitivity of DTI-derived parameters than volume measures has been demonstrated in detecting subtle hippocampal abnormalities in mild cognitive impairment subjects (Mu¨ller et al., 2006). Thus, the aim of this study is to determine, using a voxel based analysis of DTI, whether AD and FTD exhibited differential grey matter microstructural alterations in the early stage. Methods: Twelve AD subjects (71611 years), 8 FTD subjects (6666 years) and 7 controls (6067 years) were included. DTI scans were obtained using a 1.5 T scanner (TR/TE ¼ 9125/69 ms, voxel size 2mm3, 16 directions b¼0 et b¼800s/ mm2). Apparent Coefficient Diffusion (ADC) maps were constructed with FSL software. After normalization with SPM5, data were analysed with two sample t-tests to compare the differences between groups with age as a covariable (p<0.005 uncorrected, extent threshold 100). Results: The AD and Controls comparisons revealed a significant increase of ADC in temporo-parietal cortex in AD subjects (i.e. the hippocampus, the temporal, inferior parietal and the posterior cingulate gyrus) whereas the FTD and Controls comparisons revealed an increase of ADC in the fronto-parietal cortex in FTD subjects (i.e. the bilateral ventrolateral prefrontral, the anterior cingulate, and the dorsolateral prefrontal cortices). Conclusions: The results of this study confirm the preferential vulnerability of the temporo-parietal grey matter in AD patients. Moreover, we showed that microstructural abnormalities appeared in the frontotemporal and anterior cingulate cortex in FTD patients, early in the course of the disease. It appears from our study, that Voxel Based analysis of ADC maps is a sensitive method to explore the microstructural alteration of the grey matter but further studies are required to investigate if these imaging parameters are more efficient than atrophic ones in discriminating between these two aging dementia. P1-140
REGIONAL CHANGES IN BRAIN PERFUSION DURING REM SLEEP IN PATIENTS WITH ALZHEIMER’S DISEASE
Audrey Gabelle1, Florence Portet1, Vincent Boudousq2, Yves Dauvilliers1, Alain Besset3, Abdel kader Boulanouar4, Pierre Olivier Kotzki5, Jacques Touchon1, 1Service de Neurologie, CHU Gui de Chauliac, Montpellier, France; 2Service de Me´decine Nucle´aire, CHRU Caremeau, Nimes, France; 3INSERM U888, La Colombie`re, Montpellier, France; 4INSERM U825, CHRU Purpan, Toulouse, France; 5Service de Me´decine nucle´aire, CHRU Caremeau, Nimes, France. Contact e-mail: audreygabelle@hotmail. com Background: Alzheimer’s disease (AD) results in significant memory loss, changes in behavior, sleep disorders and loss of functional autonomy, mostly due to a deficit in cholinergic pathways. Cholinergic systems are involved in memory function and in sleep stage regulation, especially the Rapid Eye Movement (REM) stage. Changes in brain perfusion during sleep in healthy subjects by single-photon emission computed tomography (ECD-SPECT) have been shown. The SPECT imaging of AD patients shows temporoparietal perfusion reduction. Our objectives were to determine if SPECT cortical perfusion patterns are different during awakening when compared to REM sleep in patients with AD. We also aimed at determining whether analysis of brain perfusion changes could be used in support of positive diagnosis of AD. Methods: Eleven patients with probable AD underwent clinical, neuropsychological, polysomnography and 99mTcECD SPECT investigations. Two SPECT investigations were performed, one during awakening and one during REM sleep stage highlighted by polysomnography. The order of SPECT was random. A Statistical Parametric Mapping (SPM5) technique was used to determine the regional brain perfusion difference between basal state and REM stage. Results: A hypoperfusion in the parieto-temporal area is observed in SPECT of each patient at basal state. During REM sleep, perfusion in the left inner temporal and in a large left predominant fronto-parietal area is increased. Conclusions: This is the first study to evaluate brain perfusion changes during REM sleep in patients with AD. Our findings support the hypothesis of compensatory mechanisms in the temporal and fronto-parietal area of AD patients during REM sleep.
P1-141
THE NIH TOOLBOX FOR ASSESSMENT OF NEUROLOGICAL AND BEHAVIORAL FUNCTION
Hugh C. Hendrie1,2, Richard Gershon3, David Cella3, Cindy Nowinski3, Molly V. Wagster4, Richard Havlik5, Nathan Fox6, Christianna Purnell1,2, 1 Indiana University Center for Aging Research, Indianapolis, IN, USA; 2 Regenstrief Institute, Inc., Indianapolis, IN, USA; 3NorthShore University Health System, Evanston, IL, USA; 4National Institute on Aging, Bethesda, MD, USA; 5Westat, Inc., Rockville, MD, USA; 6University of Maryland, College Park, MD, USA. Contact e-mail: [email protected] Background: The NIH Toolbox for Assessment of Neurological and Behavioral Function is a five- year project to identify, create and validate brief comprehensive assessment tools to measure outcomes in longitudinal, epidemiological and intervention studies across the life span in the areas of cognition, emotion, motor and sensory function. The project is one of the initiatives in the NIH Blueprint for Neuroscience Research. This presentation will provide an update on its progress with emphasis on its adaptability and accessibility for use with diverse groups. Methods: While many epidemiological studies collect information on cognition and emotion as well as motor and sensory function, there is little consistency in actual measures used across studies. As a result, between study comparisons and data pooling is difficult if not impossible. Common, validated measures of these indicators of neural and behavioral health could then be used as a form of ‘‘common currency’’ across study designs and populations. This would maximize yield from these large and expensive studies with minimal increase in subject burden and cost. Results: The NIH Toolbox construction is in two phases. Phase 1, now almost completed, included domain and sub-domain selection, instrument selection, and instrument development, including refining and calibrating where needed. Phase 2 will include instrument validation as well as a study of a large random sample of the general community dwelling population. As part of Phase 1, the selected instruments were reviewed by expert teams to ensure acceptability by individuals at different age groups from children to the elderly as well as by the handicapped. Conclusions: The NIH Toolbox will provide an opportunity to consistently measure cognition, emotion, motor and sensory function over the life span. As diseases of the elderly frequently have their genesis much earlier in life, this may provide a way to identify the early indicators and risk factors for these diseases. P1-142
METACOGNITIVE MONITORING ABILITIES AND AMYLOID DEPOSITION IMAGING IN NORMAL ELDERLY INDIVIDUALS
Audrey Perrotin1, Beth C. Mormino1, Cindee M. Madison1, Amynta O. Hayenga1, William J. Jagust2, 1Helen Wills Neuroscience Institute, Berkeley, CA, USA; 2Helen Wills Neuroscience Institute; Department of Molecular Imaging and Neuroscience, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Contact e-mail: [email protected] Background: The ability to accurately self-monitor cognitive performance is essential for efficiently regulating one’s cognition (i.e. metacognition). In the context of Alzheimer’s disease (AD), metacognitive processes may help the understanding of memory impairment. To explore potential relationships with the neuropathological hallmark of AD, i.e. beta-amyloid deposition, metacognitive abilities were compared to PiB PET images in healthy elderly subjects. Methods: Thirty-two cognitively normal subjects (age: M¼73.53, SD¼5.6; MMSE: M¼28.97, SD¼1.18) underwent cognitive testing and PiB PET scanning. Cognitive measures included two episodic memory tests (CVLT and WMS-Visual Reproduction) and an executive non-memory dependent test (Stroop). A general memory composite score was also derived from the episodic memory tests. To assess metacognitive monitoring subjects were asked to make judgments about their general memory abilities (off-line monitoring) and about their performance after the completion of the three cognitive tasks (on-line monitoring). Metacognitive accuracy measures were obtained by the absolute difference between judgment and objective performance. PiB PET distribution volume ratio (DVR) images were created using Logan graphical analysis (35-90 minutes post-injection, cerebellar reference region). Correlations were conducted between voxel-wise DVR values and behavioral measures using statistical nonparametric mapping (SnPM5,
Poster Presentations P1
study not only the microstructure of the white matter brain but also that of the grey matter. Indeed, higher sensitivity of DTI-derived parameters than volume measures has been demonstrated in detecting subtle hippocampal abnormalities in mild cognitive impairment subjects (Mu¨ller et al., 2006). Thus, the aim of this study is to determine, using a voxel based analysis of DTI, whether AD and FTD exhibited differential grey matter microstructural alterations in the early stage. Methods: Twelve AD subjects (71611 years), 8 FTD subjects (6666 years) and 7 controls (6067 years) were included. DTI scans were obtained using a 1.5 T scanner (TR/TE ¼ 9125/69 ms, voxel size 2mm3, 16 directions b¼0 et b¼800s/ mm2). Apparent Coefficient Diffusion (ADC) maps were constructed with FSL software. After normalization with SPM5, data were analysed with two sample t-tests to compare the differences between groups with age as a covariable (p<0.005 uncorrected, extent threshold 100). Results: The AD and Controls comparisons revealed a significant increase of ADC in temporo-parietal cortex in AD subjects (i.e. the hippocampus, the temporal, inferior parietal and the posterior cingulate gyrus) whereas the FTD and Controls comparisons revealed an increase of ADC in the fronto-parietal cortex in FTD subjects (i.e. the bilateral ventrolateral prefrontral, the anterior cingulate, and the dorsolateral prefrontal cortices). Conclusions: The results of this study confirm the preferential vulnerability of the temporo-parietal grey matter in AD patients. Moreover, we showed that microstructural abnormalities appeared in the frontotemporal and anterior cingulate cortex in FTD patients, early in the course of the disease. It appears from our study, that Voxel Based analysis of ADC maps is a sensitive method to explore the microstructural alteration of the grey matter but further studies are required to investigate if these imaging parameters are more efficient than atrophic ones in discriminating between these two aging dementia. P1-140
REGIONAL CHANGES IN BRAIN PERFUSION DURING REM SLEEP IN PATIENTS WITH ALZHEIMER’S DISEASE
Audrey Gabelle1, Florence Portet1, Vincent Boudousq2, Yves Dauvilliers1, Alain Besset3, Abdel kader Boulanouar4, Pierre Olivier Kotzki5, Jacques Touchon1, 1Service de Neurologie, CHU Gui de Chauliac, Montpellier, France; 2Service de Me´decine Nucle´aire, CHRU Caremeau, Nimes, France; 3INSERM U888, La Colombie`re, Montpellier, France; 4INSERM U825, CHRU Purpan, Toulouse, France; 5Service de Me´decine nucle´aire, CHRU Caremeau, Nimes, France. Contact e-mail: audreygabelle@hotmail. com Background: Alzheimer’s disease (AD) results in significant memory loss, changes in behavior, sleep disorders and loss of functional autonomy, mostly due to a deficit in cholinergic pathways. Cholinergic systems are involved in memory function and in sleep stage regulation, especially the Rapid Eye Movement (REM) stage. Changes in brain perfusion during sleep in healthy subjects by single-photon emission computed tomography (ECD-SPECT) have been shown. The SPECT imaging of AD patients shows temporoparietal perfusion reduction. Our objectives were to determine if SPECT cortical perfusion patterns are different during awakening when compared to REM sleep in patients with AD. We also aimed at determining whether analysis of brain perfusion changes could be used in support of positive diagnosis of AD. Methods: Eleven patients with probable AD underwent clinical, neuropsychological, polysomnography and 99mTcECD SPECT investigations. Two SPECT investigations were performed, one during awakening and one during REM sleep stage highlighted by polysomnography. The order of SPECT was random. A Statistical Parametric Mapping (SPM5) technique was used to determine the regional brain perfusion difference between basal state and REM stage. Results: A hypoperfusion in the parieto-temporal area is observed in SPECT of each patient at basal state. During REM sleep, perfusion in the left inner temporal and in a large left predominant fronto-parietal area is increased. Conclusions: This is the first study to evaluate brain perfusion changes during REM sleep in patients with AD. Our findings support the hypothesis of compensatory mechanisms in the temporal and fronto-parietal area of AD patients during REM sleep.
P1-141
THE NIH TOOLBOX FOR ASSESSMENT OF NEUROLOGICAL AND BEHAVIORAL FUNCTION
Hugh C. Hendrie1,2, Richard Gershon3, David Cella3, Cindy Nowinski3, Molly V. Wagster4, Richard Havlik5, Nathan Fox6, Christianna Purnell1,2, 1 Indiana University Center for Aging Research, Indianapolis, IN, USA; 2 Regenstrief Institute, Inc., Indianapolis, IN, USA; 3NorthShore University Health System, Evanston, IL, USA; 4National Institute on Aging, Bethesda, MD, USA; 5Westat, Inc., Rockville, MD, USA; 6University of Maryland, College Park, MD, USA. Contact e-mail: [email protected] Background: The NIH Toolbox for Assessment of Neurological and Behavioral Function is a five- year project to identify, create and validate brief comprehensive assessment tools to measure outcomes in longitudinal, epidemiological and intervention studies across the life span in the areas of cognition, emotion, motor and sensory function. The project is one of the initiatives in the NIH Blueprint for Neuroscience Research. This presentation will provide an update on its progress with emphasis on its adaptability and accessibility for use with diverse groups. Methods: While many epidemiological studies collect information on cognition and emotion as well as motor and sensory function, there is little consistency in actual measures used across studies. As a result, between study comparisons and data pooling is difficult if not impossible. Common, validated measures of these indicators of neural and behavioral health could then be used as a form of ‘‘common currency’’ across study designs and populations. This would maximize yield from these large and expensive studies with minimal increase in subject burden and cost. Results: The NIH Toolbox construction is in two phases. Phase 1, now almost completed, included domain and sub-domain selection, instrument selection, and instrument development, including refining and calibrating where needed. Phase 2 will include instrument validation as well as a study of a large random sample of the general community dwelling population. As part of Phase 1, the selected instruments were reviewed by expert teams to ensure acceptability by individuals at different age groups from children to the elderly as well as by the handicapped. Conclusions: The NIH Toolbox will provide an opportunity to consistently measure cognition, emotion, motor and sensory function over the life span. As diseases of the elderly frequently have their genesis much earlier in life, this may provide a way to identify the early indicators and risk factors for these diseases. P1-142
METACOGNITIVE MONITORING ABILITIES AND AMYLOID DEPOSITION IMAGING IN NORMAL ELDERLY INDIVIDUALS
Audrey Perrotin1, Beth C. Mormino1, Cindee M. Madison1, Amynta O. Hayenga1, William J. Jagust2, 1Helen Wills Neuroscience Institute, Berkeley, CA, USA; 2Helen Wills Neuroscience Institute; Department of Molecular Imaging and Neuroscience, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Contact e-mail: [email protected] Background: The ability to accurately self-monitor cognitive performance is essential for efficiently regulating one’s cognition (i.e. metacognition). In the context of Alzheimer’s disease (AD), metacognitive processes may help the understanding of memory impairment. To explore potential relationships with the neuropathological hallmark of AD, i.e. beta-amyloid deposition, metacognitive abilities were compared to PiB PET images in healthy elderly subjects. Methods: Thirty-two cognitively normal subjects (age: M¼73.53, SD¼5.6; MMSE: M¼28.97, SD¼1.18) underwent cognitive testing and PiB PET scanning. Cognitive measures included two episodic memory tests (CVLT and WMS-Visual Reproduction) and an executive non-memory dependent test (Stroop). A general memory composite score was also derived from the episodic memory tests. To assess metacognitive monitoring subjects were asked to make judgments about their general memory abilities (off-line monitoring) and about their performance after the completion of the three cognitive tasks (on-line monitoring). Metacognitive accuracy measures were obtained by the absolute difference between judgment and objective performance. PiB PET distribution volume ratio (DVR) images were created using Logan graphical analysis (35-90 minutes post-injection, cerebellar reference region). Correlations were conducted between voxel-wise DVR values and behavioral measures using statistical nonparametric mapping (SnPM5,