Authors: Lyoo, Chul Hyoung | Cho, Hanna | Choi, Jae Yong | Hwang, Mi Song | Hong, Sang Kyoon | Kim, Yun Joong | Ryu, Young Hoon | Lee, Myung Sik
Article Type: Short Communication
Abstract: We studied topographic distribution of tau and amyloid-β in a patient with variant Alzheimer’s disease with spastic paraparesis (VarAD) by comparing AD patients. The proband developed progressive memory impairment, dysarthria, and spastic paraparesis at age 23. Heterozygous missense mutation (L166P) was found in exon 6 of presenilin-1 gene. The proband showed prominently increased amyloid binding in striatum and cerebellum and asymmetrical tau binding in the primary sensorimotor cortex contralateral to the side more affected by spasticity. We suspect that upper motor neuron dysfunctions may be attributed to excessive abnormal tau accumulation rather than amyloid-β in the primary motor cortex.
Keywords: Alzheimer’s disease, amyloid, PET, spastic paraplegia, tau protein
DOI: 10.3233/JAD-151052
Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 671-675, 2016
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 | 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: Cho, Eun Bin | Seo, Sang Won | Kim, HoJeong | Lee, Jong-Min | Yoon, Uicheul | Im, Kiho | Kim, Geon Ha | Noh, Young | Cho, Hanna | Yoon, Cindy W. | Kim, Hee Jin | Na, Duk L.
Article Type: Research Article
Abstract: There are some studies identifying the association between kidney dysfunction and cognitive impairment through various mechanisms including small vessel disease. However, results concerning the relationship between kidney dysfunction and cortical atrophy have been inconsistent. Thus, we aimed to evaluate the relationship among kidney dysfunction, small vessel disease, and cortical thinning in probable Alzheimer's disease (AD) dementia patients. Patients consisted of 162 subjects with probable AD dementia who underwent high-resolution T1-weighted volumetric magnetic resonance imaging (MRI) scans using the same scanner. The estimated glomerular filtration rate (GFR) was calculated and divided into the quartiles of patients for comparison. Volume of white …matter hyperintensities (WMH) was automatically measured. Two neurologists counted the number of lacunes. Cortical thickness was measured using a surface-based method. GFR was not associated with WMH and the number of lacunes. However, the lowest quartile group of GFR (GFR 1) had cortical thinning in each lobe, compared to the highest quartile group of GFR (GFR 4). The topography of cortical thinning in the GFR 1 group was distributed predominantly in temporoparietal regions, compared to GFR 4. After further adjustment of small vessel disease MRI markers, the association between GFR and the cortical thinning remained. Our findings suggested that kidney dysfunction, represented by GFR, was related to temporoparietal thinning independent of small vessel disease in probable AD dementia patients. Show more
Keywords: Alzheimer's disease, cortical thinning, glomerular filtration rate, kidney function
DOI: 10.3233/JAD-2012-121180
Citation: Journal of Alzheimer's Disease, vol. 33, no. 4, pp. 961-968, 2013
Clinical Characteristic in Primary Progressive Aphasia in Relation to Alzheimer’s Disease Biomarkers
Authors: Kang, Sung Hoon | Cho, Hanna | Shin, Jiho | Kim, Hang-Rai | Noh, Young | Kim, Eun-Joo | Lyoo, Chul Hyoung | Jang, Hyemin | Kim, Hee Jin | Koh, Seong-Beom | Na, Duk L. | Suh, Mee Kyung | Seo, Sang Won
Article Type: Research Article
Abstract: Background: Primary progressive aphasia (PPA) is associated with amyloid-β (Aβ) pathology. However, clinical feature of PPA based on Aβ positivity remains unclear. Objective: We aimed to assess the prevalence of Aβ positivity in patients with PPA and compare the clinical characteristics of patients with Aβ-positive (A+) and Aβ-negative (A–) PPA. Further, we applied Aβ and tau classification system (AT system) in patients with PPA for whom additional information of in vivo tau biomarker was available. Methods: We recruited 110 patients with PPA (41 semantic [svPPA], 27 non-fluent [nfvPPA], 32 logopenic [lvPPA], and 10 unclassified [ucPPA]) who underwent Aβ-PET imaging at …multi centers. The extent of language impairment and cortical atrophy were compared between the A+ and A–PPA subgroups using general linear models. Results: The prevalence of Aβ positivity was highest in patients with lvPPA (81.3%), followed by ucPPA (60.0%), nfvPPA (18.5%), and svPPA (9.8%). The A+ PPA subgroup manifested cortical atrophy mainly in the left superior temporal/inferior parietal regions and had lower repetition scores compared to the A–PPA subgroup. Further, we observed that more than 90% (13/14) of the patients with A+ PPA had tau deposition. Conclusion: Our findings will help clinicians understand the patterns of language impairment and cortical atrophy in patients with PPA based on Aβ deposition. Considering that most of the A+ PPA patents are tau positive, understanding the influence of Alzheimer’s disease biomarkers on PPA might provide an opportunity for these patients to participate in clinical trials aimed for treating atypical Alzheimer’s disease. Show more
Keywords: Amyloid-β, biomarker, language, primary progressive aphasia, tau
DOI: 10.3233/JAD-210392
Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 633-645, 2021
Authors: Yoo, Han Soo | Kim, Han-Kyeol | Lee, Jae-Hoon | Chun, Joong-Hyun | Lee, Hye Sun | Grothe, Michel J. | Teipel, Stefan | Cavedo, Enrica | Vergallo, Andrea | Hampel, Harald | Ryu, Young Hoon | Cho, Hanna | Lyoo, Chul Hyoung
Article Type: Research Article
Abstract: Background: Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer’s disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. Objective: To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. Methods: In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [Aβ]-negative cognitively unimpaired, 6 Aβ-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, 18 F-florbetaben PET for Aβ, 18 F-flortaucipir PET for tau, and detailed cognitive testing longitudinally. We investigated …the baseline and longitudinal association of BF volume with Aβ and tau standardized uptake value ratio and cognition. Results: Cross-sectionally, lower BF volume was not independently associated with higher cortical Aβ, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster Aβ accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline Aβ and tau burden. Conclusions: Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function. Show more
Keywords: Alzheimer’s disease, amyloid-beta, basal forebrain, cognition, tau
DOI: 10.3233/JAD-230975
Citation: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 145-159, 2024
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
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: 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
