Authors: Cho, Hanna | Seo, Sang Won | Kim, Jung-Hyun | Suh, Mee Kyung | Lee, Jae-Hong | Choe, Yearn Seong | Lee, Kyung-Han | Kim, Jae Seung | Kim, Geon Ha | Noh, Young | Ye, Byoung Seok | Kim, Hee Jin | Yoon, Cindy W. | Chin, Juhee | Na, Duk L.
Article Type: Research Article
Abstract: Background: Patients with early-onset Alzheimer’s disease (EOAD) may differ from those with late-onset Alzheimer’s disease (LOAD) in cognitive impairment profiles and clinical course. Postmortem studies also reported that EOAD has a greater pathologic burden than LOAD. We examined the effects of age at onset on the burden and distribution of amyloid plaques in patients with AD, using a statistical parametric mapping (SPM) and regions of interest (ROIs) analyses of the Pittsburgh compound B (PiB)-PET. Methods: We initially recruited 72 patients with AD who had completed the [11 C] PiB-PET scan, but four patients were excluded due to familial AD or …incomplete MRI data. Of the 68 patients, 61 were classified as PiB-positive (PiB+) and seven as PiB-negative (PiB–) using the measured global PiB uptake ratio values. Of the 61 patients with PiB+ AD, in order to maximize the effect of onset age, we excluded 20 patients in their 60 s. Thus among the remaining 41 patients, the amyloid deposition of only 17 patients with EOAD (age onset <60 years) and 24 patients with LOAD (onset age ≥70 years) were compared. Results: There were no significant differences in the global mean PiB index between EOAD and LOAD patients, whereas SPM and ROIs analyses showed that those with EOAD retained higher levels of PiB in the bilateral basal ganglia, bilateral thalamus, left superior temporal cortex, and left cuneus compared to those with LOAD. Conclusion: Our findings demonstrated that EOAD patients differed from those with LOAD in the topography of amyloid deposition, which may partly account for the findings from previous studies that extrapyramidal symptoms and frontal dysfunction are more common in EOAD than in LOAD patients. Show more
Keywords: Alzheimer's disease, amyloid, early onset, onset age, Pittsburgh compound B (PiB)-PET
DOI: 10.3233/JAD-121927
Citation: Journal of Alzheimer's Disease, vol. 35, no. 4, pp. 813-821, 2013
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: Noh, Young | Seo, Sang Won | Jeon, Seun | Lee, Jong Min | Kim, Jung-Hyun | Kim, Geon Ha | Cho, Hanna | Yoon, Cindy W. | Kim, Hee Jin | Ye, Byoung Seok | Kim, Sung Tae | Choe, Yearn Seong | Lee, Kyung-Han | Kim, Jae Seung | Ewers, Michael | Weiner, Michael W. | Lee, Jae-Hong | Werring, David J. | Kang, Dae Ryong | Kim, Chang Soo | Na, Duk L.
Article Type: Research Article
Abstract: Previous preclinical studies have suggested a close relationship between cerebrovascular disease (CVD) and Alzheimer's disease. However, a direct correlation between CVD and amyloid burden has not yet been shown in humans. If there is a relationship between CVD and amyloid burden, it is possible that the apolipoprotein E4 (APOE4) genotype may have an effect on this relationship because APOE4 is a risk factor for the development of AD. We therefore evaluated the effects of APOE4 on the relationship between white matter hyperintensities (WMH), a marker of CVD, and amyloid burden, measured by 11 C-Pittsburgh compound B (PiB) PET. We recruited …53 patients with subcortical vascular cognitive impairments, who had both WMH on MRI and amyloid deposition assessed by PiB PET. Twenty-two of these patients were APOE4 carriers (41.5%). In the APOE4 non-carriers, a significant positive correlation was shown between the volume of WMH and PiB retention (β = 7.0 × 10−3 , p = 0.034) while no significant correlation was found in APOE4 carriers (β = −9.0 × 10−3 , p = 0.085). Statistical parametric mapping analyses in APOE4 non-carriers showed that WMH were associated with PiB retention in the bilateral medial occipitotemporal gyrus, cuneus, and superior cerebellum. Our results suggested that WMH are correlated with amyloid burden especially in the posterior brain regions in APOE4 non-carriers. However, this correlation was not observed in APOE4 carriers, perhaps because in these subjects the influence of APOE4 overrides the effect of CVD. Show more
Keywords: Alzheimer's disease, amyloid burden, apolipoprotein E4, cerebrovascular disease
DOI: 10.3233/JAD-130461
Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 877-886, 2014
Authors: Noh, Young | Seo, Sang Won | Jeon, Seun | Lee, Jong Min | Kim, Jae Seung | Lee, Jae-Hong | Kim, Jung-Hyun | Kim, Geon Ha | Ye, Byoung Seok | Cho, Hanna | Kim, Hee Jin | Yoon, Cindy W | Choe, Yearn Seong | Lee, Kyung-Han | Weiner, Michael W. | Na, Duk L.
Article Type: Research Article
Abstract: Background: Some patients clinically diagnosed with subcortical vascular cognitive impairment (SVCI) have co-morbidity with AD pathology. Objective: We investigated topographical differences in amyloid burden between SVCI and Alzheimer’s disease type cognitive impairment (ADCI) using [11 C] Pittsburgh compound B (PiB) positron emission tomography (PET). The purpose of this study was to investigate the role of cerebrovascular disease (CVD) in amyloid deposition. Methods: We recruited 44 patients with SVCI and 44 patients with ADCI (amnestic mild cognitive impairment or Alzheimer’s disease) with absent or minimal white matter hyperintensities, all with PiB-positive PET scans [PiB+]. As controls, we included 13 participants with …normal cognition and PiB-negative scans. We divided the SVCI and ADCI patients into three groups according to global PiB retention ratio of SVCI, and then compared the tertiles in terms of the distribution of PiB retention using statistical parametric mapping analyses. Lobar to global PiB retention ratio and asymmetry indices were also compared between SVCI and ADCI groups Results: Compared to PiB+ ADCI patients, PiB+ SVCI patients exhibited: 1) increased left-right asymmetry, and increased anterior-posterior difference; and 2) increased PiB retention in the parietal cortex, the occipital cortex and the precuneus-posterior cingulate cortex. In contrast, ADCI patients showed increased PiB retention in the striatum. When stratified by level of PiB retention, each group showed different characteristics. Conclusion: Our results showed that the distribution of amyloid deposition differed between patients with PiB+ SVCI and ADCI. These suggest that CVD contribute to and alter the known progression pattern in amyloid deposition in Alzheimer’s disease. Show more
Keywords: Alzheimer’s disease, cerebrovascular disease, magnetic resonance imaging, positron emission tomography, vascular dementia ∥
DOI: 10.3233/JAD-150832
Citation: Journal of Alzheimer's Disease, vol. 54, no. 3, pp. 1015-1026, 2016
