- Email: [email protected]
CHOLINERGIC ENHANCEMENT INCREASES REGIONAL CEREBRAL BLOOD FLOW TO THE POSTERIOR CINGULATE CORTEX IN MILD ALZHEIMER’S DISEASE
Poster Presentations: Saturday, July 23, 2016 IC-P-040
USING WHITE MATTER SEED REGIONS PRODUCES STRONGER AND MORE COMPLEX STRUCTURAL NETWORKS IN HEALTHY ELDERLY SUBJECTS AND SUBJECTS WITH ALZHEIMER’S DISEASE
Lauren Zajac, Bang-Bon Koo, Ronald Killiany, Boston University School of Medicine, Boston, MA, USA. Contact e-mail: [email protected] Background: Whole-brain structural networks derived from MRI
data are built from fiber tracts, which are generated using measurements of the orientation of water motion embedded in diffusion tensor imaging (DTI) or high angular resolution diffusion imaging (HARDI) data. These tracts need starting points, or seeds, and ending points, or targets. We investigated how using gray matter (GM) or white matter (WM) regions of interest (ROIs) as seeds impacts structural networks derived from DTI and HARDI data. Methods: Data from healthy elderly controls and individuals with Alzheimer’s disease (AD) were selected from DTI datasets in the ADNI database and HARDI datasets collected at the Center for Biomedical Imaging. These data were used to construct two whole-brain networks for each subject. Probabilistic tracts were formed using WM-ROIs or GM-ROIs as seeds and GM-ROIs as targets. GM-ROIs were defined using the Desikan-Killiany FreeSurfer atlas. WM-ROIs were defined as a strip of voxels one voxel below the gray/white border of each GM-ROI. Comparisons were performed using the Network Based Statistic (NBS) toolbox. Results: In the DTI data, networks derived using WM-ROIs had approximately 400 more probabilistic connections than those derived from GM-ROIs. GM-ROI networks shared 94% of their connections with WM-ROI networks. Within-group NBS revealed a stronger subnetwork in WM-ROI networks compared to GM-ROI networks (p<0.001) in both controls and AD. In the HARDI data, WM-ROI networks had approximately 530 more probabilistic connections than GM-ROI networks. Again, GM-ROI networks shared 94% of their connections with WM-ROI networks. Within-group NBS revealed a stronger subnetwork in WM-ROI networks compared to GM-ROI networks (p¼0.029) in both groups. Between-group NBS performed on networks generated from DTI data revealed a stronger subnetwork in controls compared to AD when using WM-ROI networks (p¼0.004) and GM-ROI networks (p¼0.0326). Conclusions: Generating robust networks is an important prerequisite for network analyses because it prevents artifactual findings that can arise when networks with few and/or weak connections are used. Our analyses using DTI data show that WM-ROI networks are more sensitive to differences between control and AD, and ongoing analyses are exploring whether the same is true in HARDI data. IC-P-041
CHOLINERGIC ENHANCEMENT INCREASES REGIONAL CEREBRAL BLOOD FLOW TO THE POSTERIOR CINGULATE CORTEX IN MILD ALZHEIMER’S DISEASE
Tomomichi Iizuka1, Masashi Kameyama2,3, 1Fukujuji Hospital, Kiyose, Japan; 2National Center for Global Health and Medicine, Tokyo, Japan; 3 Keio University, Tokyo, Japan. Contact e-mail: [email protected] Background: The brain region that shows reductions in regional ce-
rebral blood flow (rCBF) earliest is posterior cingulate cortex (PCC), which is thought to have relation with cognitive function. We made a hypothesis that the PCC hypoperfusion is due to cholinergic dysfunction and can be restored by cholinergic enhancement. This present longitudinal study aimed to detect the restoration of PCC rCBF in response to donepezil, an acetylcholine esterase in-
P35
hibitor. Methods: We evaluated rCBF changes in the PCC, precuneus and anterior cingulate cortex (ACC) using perfusion single photon emission computed tomography (SPECT), statistical analysis and region of interest (ROI) analysis. We allocated 36 patients with mild AD to either responder or non-responder groups based on changes in mini-mental state examination (MMSE) scores. The patients were followed-up for 18 months. Results: The PCC rCBF significantly increased in responders after six months of donepezil therapy. Statistical maps at baseline showed typical decreased pattern of mild AD and obvious rCBF restoration in the bilateral PCC at six months in responders. Changes in MMSE scores and AD assessment scale cognitive scores significantly correlated with rCBF changes in the PCC of responders. Conclusions: Cholinergic enhancement restored PCC rCBF under the 3 conditions of mild AD, responders and short follow-up interval and that increase correlated with improved cognitive function. These findings support our hypothesis that PCC rCBF reflects cholinergic function in AD patients.
IC-P-042
LEFT PREFRONTAL GLOBAL CONNECTIVITY ENHANCES COGNITIVE RESERVE IN ALZHEIMER’S DISEASE
Nicolai Franzmeier1, Michael Ewers2, Alzheimer’s Disease Neuroimaging Initiative, 1Institute for Stroke and Dementia Research, M€unchen, Germany; 2 Institute for Stroke and Dementia Research, Klinikum der Universitaet Muenchen, Ludwig-Maximilians-University Munich, Munich, Germany. Contact e-mail: [email protected] Background: Previous studies suggest that in Alzheimer’s disease
(AD), patients with higher cognitive reserve (CR) can maintain memory performance relatively well in the presence of neural injury such as measured by parietal FDG-PET hypometabolism. However, the functional brain mechanisms that underlie CR are not known. We hypothesized firstly, that higher global connectivity of the left prefrontal cortex (LPFC), a region known to support cognitive control, is associated with higher CR (as measured by education). Secondly, we hypothesized, that higher LPFC connectivity is associated with a reduced effect of parietal FDG-PET hypometabolism onto memory performance in prodromal AD. Methods: Our sample comprised 76 subjects with mild cognitive impairment (MCI) including 44 with a positive amyloid-PET (MCI-Ab+) and 32 with a negative amyloid-PET scan (MCI-Ab-), recruited within the Alzheimer’s Disease Neuroimaging Initiative. We conducted seed-based connectivity analysis in each subject, computing Pearson-Moment correlations of the resting-state fMRI signal between an 8mm spherical ROI in the LPFC (BA 6) and each voxel in the grey matter. To yield the global LPFC
USING WHITE MATTER SEED REGIONS PRODUCES STRONGER AND MORE COMPLEX STRUCTURAL NETWORKS IN HEALTHY ELDERLY SUBJECTS AND SUBJECTS WITH ALZHEIMER’S DISEASE
Lauren Zajac, Bang-Bon Koo, Ronald Killiany, Boston University School of Medicine, Boston, MA, USA. Contact e-mail: [email protected] Background: Whole-brain structural networks derived from MRI
data are built from fiber tracts, which are generated using measurements of the orientation of water motion embedded in diffusion tensor imaging (DTI) or high angular resolution diffusion imaging (HARDI) data. These tracts need starting points, or seeds, and ending points, or targets. We investigated how using gray matter (GM) or white matter (WM) regions of interest (ROIs) as seeds impacts structural networks derived from DTI and HARDI data. Methods: Data from healthy elderly controls and individuals with Alzheimer’s disease (AD) were selected from DTI datasets in the ADNI database and HARDI datasets collected at the Center for Biomedical Imaging. These data were used to construct two whole-brain networks for each subject. Probabilistic tracts were formed using WM-ROIs or GM-ROIs as seeds and GM-ROIs as targets. GM-ROIs were defined using the Desikan-Killiany FreeSurfer atlas. WM-ROIs were defined as a strip of voxels one voxel below the gray/white border of each GM-ROI. Comparisons were performed using the Network Based Statistic (NBS) toolbox. Results: In the DTI data, networks derived using WM-ROIs had approximately 400 more probabilistic connections than those derived from GM-ROIs. GM-ROI networks shared 94% of their connections with WM-ROI networks. Within-group NBS revealed a stronger subnetwork in WM-ROI networks compared to GM-ROI networks (p<0.001) in both controls and AD. In the HARDI data, WM-ROI networks had approximately 530 more probabilistic connections than GM-ROI networks. Again, GM-ROI networks shared 94% of their connections with WM-ROI networks. Within-group NBS revealed a stronger subnetwork in WM-ROI networks compared to GM-ROI networks (p¼0.029) in both groups. Between-group NBS performed on networks generated from DTI data revealed a stronger subnetwork in controls compared to AD when using WM-ROI networks (p¼0.004) and GM-ROI networks (p¼0.0326). Conclusions: Generating robust networks is an important prerequisite for network analyses because it prevents artifactual findings that can arise when networks with few and/or weak connections are used. Our analyses using DTI data show that WM-ROI networks are more sensitive to differences between control and AD, and ongoing analyses are exploring whether the same is true in HARDI data. IC-P-041
CHOLINERGIC ENHANCEMENT INCREASES REGIONAL CEREBRAL BLOOD FLOW TO THE POSTERIOR CINGULATE CORTEX IN MILD ALZHEIMER’S DISEASE
Tomomichi Iizuka1, Masashi Kameyama2,3, 1Fukujuji Hospital, Kiyose, Japan; 2National Center for Global Health and Medicine, Tokyo, Japan; 3 Keio University, Tokyo, Japan. Contact e-mail: [email protected] Background: The brain region that shows reductions in regional ce-
rebral blood flow (rCBF) earliest is posterior cingulate cortex (PCC), which is thought to have relation with cognitive function. We made a hypothesis that the PCC hypoperfusion is due to cholinergic dysfunction and can be restored by cholinergic enhancement. This present longitudinal study aimed to detect the restoration of PCC rCBF in response to donepezil, an acetylcholine esterase in-
P35
hibitor. Methods: We evaluated rCBF changes in the PCC, precuneus and anterior cingulate cortex (ACC) using perfusion single photon emission computed tomography (SPECT), statistical analysis and region of interest (ROI) analysis. We allocated 36 patients with mild AD to either responder or non-responder groups based on changes in mini-mental state examination (MMSE) scores. The patients were followed-up for 18 months. Results: The PCC rCBF significantly increased in responders after six months of donepezil therapy. Statistical maps at baseline showed typical decreased pattern of mild AD and obvious rCBF restoration in the bilateral PCC at six months in responders. Changes in MMSE scores and AD assessment scale cognitive scores significantly correlated with rCBF changes in the PCC of responders. Conclusions: Cholinergic enhancement restored PCC rCBF under the 3 conditions of mild AD, responders and short follow-up interval and that increase correlated with improved cognitive function. These findings support our hypothesis that PCC rCBF reflects cholinergic function in AD patients.
IC-P-042
LEFT PREFRONTAL GLOBAL CONNECTIVITY ENHANCES COGNITIVE RESERVE IN ALZHEIMER’S DISEASE
Nicolai Franzmeier1, Michael Ewers2, Alzheimer’s Disease Neuroimaging Initiative, 1Institute for Stroke and Dementia Research, M€unchen, Germany; 2 Institute for Stroke and Dementia Research, Klinikum der Universitaet Muenchen, Ludwig-Maximilians-University Munich, Munich, Germany. Contact e-mail: [email protected] Background: Previous studies suggest that in Alzheimer’s disease
(AD), patients with higher cognitive reserve (CR) can maintain memory performance relatively well in the presence of neural injury such as measured by parietal FDG-PET hypometabolism. However, the functional brain mechanisms that underlie CR are not known. We hypothesized firstly, that higher global connectivity of the left prefrontal cortex (LPFC), a region known to support cognitive control, is associated with higher CR (as measured by education). Secondly, we hypothesized, that higher LPFC connectivity is associated with a reduced effect of parietal FDG-PET hypometabolism onto memory performance in prodromal AD. Methods: Our sample comprised 76 subjects with mild cognitive impairment (MCI) including 44 with a positive amyloid-PET (MCI-Ab+) and 32 with a negative amyloid-PET scan (MCI-Ab-), recruited within the Alzheimer’s Disease Neuroimaging Initiative. We conducted seed-based connectivity analysis in each subject, computing Pearson-Moment correlations of the resting-state fMRI signal between an 8mm spherical ROI in the LPFC (BA 6) and each voxel in the grey matter. To yield the global LPFC