Authors: Kim, Hee Jin | Im, Kiho | Kwon, Hunki | Lee, Jong Min | Ye, Byoung Seok | Kim, Yeo Jin | Cho, Hanna | Choe, Yearn Seong | Lee, Kyung Han | Kim, Sung Tae | Kim, Jae Seung | Lee, Jae Hong | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: There is growing evidence that the human brain is a large scale complex network. The structural network is reported to be disrupted in cognitively impaired patients. However, there have been few studies evaluating the effects of amyloid and small vessel disease (SVD) markers, the common causes of cognitive impairment, on structural networks. Thus, we evaluated the association between amyloid and SVD burdens and structural networks using diffusion tensor imaging (DTI). Furthermore, we determined if network parameters predict cognitive impairments. Graph theoretical analysis was applied to DTI data from 232 cognitively impaired patients with varying degrees of amyloid and SVD burdens. …All patients underwent Pittsburgh compound-B (PiB) PET to detect amyloid burden, MRI to detect markers of SVD, including the volume of white matter hyperintensities and the number of lacunes, and detailed neuropsychological testing. The whole-brain network was assessed by network parameters of integration (shortest path length, global efficiency) and segregation (clustering coefficient, transitivity, modularity). PiB retention ratio was not associated with any white matter network parameters. Greater white matter hyperintensity volumes or lacunae numbers were significantly associated with decreased network integration (increased shortest path length, decreased global efficiency) and increased network segregation (increased clustering coefficient, increased transitivity, increased modularity). Decreased network integration or increased network segregation were associated with poor performances in attention, language, visuospatial, memory, and frontal-executive functions. Our results suggest that SVD alters white matter network integration and segregation, which further predicts cognitive dysfunction. Show more
Keywords: Amyloid, diffusion tensor imaging, graph theory, small vessel disease, white matter network
DOI: 10.3233/JAD-141623
Citation: Journal of Alzheimer's Disease, vol. 44, no. 3, pp. 963-975, 2015
Authors: Lee, Juyoun | Cho, Hanna | Jeon, Seun | Kim, Hee Jin | Kim, Yeo Jin | Lee, Jeongmin | Kim, Sung Tae | Lee, Jong-Min | Chin, Juhee | Lockhart, Samuel N. | Lee, Ae Young | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: Background: Sex effects on the progression of Alzheimer’s disease (AD) have received less attention than other demographic factors, including onset age and education. Objective: The aim of this study was to investigate whether sex affected cortical thinning in the disease progression of AD. Methods: We prospectively recruited 36 patients with early-stage AD and 14 people with normal cognition. All subjects were assessed with magnetic resonance imaging at baseline, Year 1, Year 3, and Year 5. We performed cortical thickness analyses using surface-based morphometry on magnetic resonance imaging. Results: Women with AD showed more rapid cortical thinning in the left dorsolateral …frontal cortex, left superior temporal gyrus, bilateral temporo-parietal association cortices, bilateral anterior cingulate gyri, bilateral medial frontal cortices, and bilateral occipital cortices over 5 years than men with AD, even though there was no difference in cortical thickness at baseline. In contrast, there were no regions of significantly more rapid atrophy in men with AD. Conclusions: Our findings suggest that women deteriorate faster than men in the progression of AD. Show more
Keywords: Alzheimer’s disease, cognitive reserve, cortical thickness, longitudinal study, sex
DOI: 10.3233/JAD-180049
Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 641-649, 2018
Authors: Kim, Hee Jin | Cha, Jungho | Lee, Jong-Min | Shin, Ji Soo | Jung, Na-Yeon | Kim, Yeo Jin | Choe, Yearn Seong | Lee, Kyung Han | Kim, Sung Tae | Kim, Jae Seung | Lee, Jae Hong | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: Background: Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer’s disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. Objective: The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. Methods: In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(–) subcortical vascular dementia (SVaD), 13 …mixed dementia patients, and 65 normal controls. Results: When the resting-state DMN of PiB(+) AD and PiB(–) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(–) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(–) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(–) SVaD patients were compared, the PiB(–) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(–) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. Conclusions: Our findings suggest that in PiB(+) AD and PiB(–) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden. Show more
Keywords: Alzheimer’s disease, amyloid, central executive network, default mode network, resting-state functional MRI, small vessel disease, subcortical vascular dementia,
DOI: 10.3233/JAD-150637
Citation: Journal of Alzheimer's Disease, vol. 50, no. 3, pp. 709-718, 2016
Authors: Kim, Yeo Jin | Cho, Hanna | Kim, Yun Joong | Ki, Chang-Seok | Chung, Sun Ju | Ye, Byoung Seok | Kim, Hee Jin | Kim, Jung-Hyun | Kim, Sung Tae | Lee, Kyung Han | Jeon, Seun | Lee, Jong-Min | Chin, Juhee | Kim, Jeong-Hun | Na, Duk L. | Seong, Joon-Kyung | Seo, Sang Won
Article Type: Research Article
Abstract: Apolipoprotein E4 (APOE4) is a genetic risk factor for developing Alzheimer's disease (AD). Once AD manifests clinically, however, the effects of APOE4 are less clear. Therefore, we investigated the longitudinal effects of APOE4 on topographical changes in AD patient brain atrophy. We prospectively recruited 35 patients with AD (19 APOE4 carriers and 16 non-carriers), and 14 normal controls, then followed them for five years. We measured hippocampal deformities and cortical thickness. Hippocampal comparison between APOE4 carriers and non-carriers with AD showed carriers had rapid changes in the head and body, while non-carriers had rapid changes in a small portion of …the body. Cortical thickness comparison between APOE4 carriers and non-carriers with AD dementia showed carriers had rapid thinning in the lateral frontal, temporal, and parietal regions, while no region showed more rapid cortical thinning in non-carriers than in carriers. These findings underlined the importance of the APOE4 allele for designing and interpreting future treatment trials in patients with AD dementia. Show more
Keywords: APOE4 allele, cortical thickness, dementia with Alzheimer's disease, hippocampal deformities, longitudinal study
DOI: 10.3233/JAD-141773
Citation: Journal of Alzheimer's Disease, vol. 44, no. 4, pp. 1075-1085, 2015
Authors: Cho, Hanna | Kim, Jeong-Hun | Kim, Changsoo | Ye, Byoung Seok | Kim, Hee Jin | Yoon, Cindy W. | Noh, Young | Kim, Geon Ha | Kim, Yeo Jin | Kim, Jung-Hyun | Kim, Chang-Hun | Kang, Sue J. | Chin, Juhee | Kim, Sung Tae | Lee, Kyung-Han | Na, Duk L. | Seong, Joon-Kyung | Seo, Sang Won
Article Type: Research Article
Abstract: Background: A large number of Alzheimer’s disease (AD) studies have focused on medial temporal and cortical atrophy, while changes in the basal ganglia or thalamus have received less attention. Objective: The aim of this study was to investigate the existence of progressive topographical shape changes in the basal ganglia (caudate nucleus, putamen, and globus pallidus) and thalamus concurrent with AD disease progression over three years. This study also examined whether declines in volumes of the basal ganglia or thalamus might be responsible for cognitive decline in patients with AD. Methods: Thirty-six patients with early stage AD and 14 normal control …subjects were prospectively recruited for this study. All subjects were assessed with neuropsychological tests and MRI at baseline and Years 1 and 3. A longitudinal shape analysis of the basal ganglia and thalamus was performed by employing a boundary surface-based shape analysis method. Results: AD patients exhibited specific regional atrophy in the right caudate nucleus and the bilateral putamen at baseline, and as the disease progressed, regional atrophic changes in the left caudate nucleus were found to conform to a distinct topography after controlling the total brain volume. Volumetric decline of the caudate nucleus and putamen correlated with cognitive decline in frontal function after controlling for age, gender, education, follow-up years, and total brain volume changes. Conclusion: Our findings suggest that shape changes of the basal ganglia occurred regardless of whole brain atrophy as AD progressed and were also responsible for cognitive decline that was observed from the frontal function tests. Show more
Keywords: Alzheimer's disease, basal ganglia, caudate nucleus, globus pallidus, putamen, shape, thalamus
DOI: 10.3233/JAD-132072
Citation: Journal of Alzheimer's Disease, vol. 40, no. 2, pp. 285-295, 2014
Authors: Kim, Hee Jin | Cho, Hanna | Werring, David J. | Jang, Young Kyoung | Kim, Yeo Jin | Lee, Jin San | Lee, Juyoun | Jun, Soomin | Park, Seongbeom | Ryu, Young Hoon | Choi, Jae Yong | Cho, Young Seok | Moon, Seung Hwan | Na, Duk L. | Lyoo, Chul Hyoung | Seo, Sang Won
Article Type: Short Communication
Abstract: Cerebrovascular deposition of amyloid-β, known as cerebral amyloid angiopathy (CAA), is associated with MRI findings of lobar hemorrhage, cerebral microbleeds, and cortical superficial siderosis. Although pathological studies suggest that tau may co-localize with vascular amyloid, this has not yet been investigated in CAA in vivo . Three patients with probable CAA underwent 11 C-Pittsburgh Compound B (PiB) PET or 18 F-florbetaben PET to evaluate amyloid burden, and 18 F-AV-1451 PET to evaluate paired helical filament tau burden. Regions that had cerebral microbleeds or cortical superficial siderosis largely overlapped with those showing increased 18 F-AV-1451. Our preliminary study raised the possibility …that lobar cerebral microbleeds, and cortical superficial siderosis, which are characteristic markers of vascular amyloid, may be associated with local production of paired helical filament tau. Show more
Keywords: Cerebral amyloid angiopathy, cortical superficial siderosis, 18F-AV-1451 PET, lobar cerebral microbleeds, tau
DOI: 10.3233/JAD-161139
Citation: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 711-716, 2017