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, Si Eun | Woo, Sookyoung | Kim, Seon Woo | Chin, Juhee | Kim, Hee Jin | Lee, Byung In | Park, Jinse | Park, Kyung Won | Kang, Do-Young | Noh, Young | Ye, Byoung Seok | Yoo, Han Soo | Lee, Jin San | Kim, Yeshin | Kim, Seung Joo | Cho, Soo Hyun | Na, Duk L. | Lockhart, Samuel N. | Jang, Hyemin | Seo, Sang Won
Article Type: Research Article
Abstract: Background: Most clinical trials focus on amyloid-β positive (Aβ+) amnestic mild cognitive impairment (aMCI), but screening failures are high because only a half of patients with aMCI are positive on Aβ PET. Therefore, it becomes necessary for clinicians to predict which patients will have Aβ biomarker. Objective: We aimed to compare clinical factors, neuropsychological (NP) profiles, and apolipoprotein E (APOE ) genotype between Aβ+ aMCI and Aβ–aMCI and to develop a clinically useful prediction model of Aβ positivity on PET (PET-Aβ+) in aMCI using a nomogram. Methods: We recruited 523 aMCI patients who underwent Aβ PET imaging in a nation-wide …multicenter cohort. The results of NP measures were divided into following subgroups: 1) Stage (Early and Late-stage), 2) Modality (Visual, Verbal, and Both), 3) Recognition failure, and 4) Multiplicity (Single and Multiple). A nomogram for PET-Aβ+ in aMCI patients was constructed using a logistic regression model. Results: PET-Aβ+ had significant associations with NP profiles for several items, including high Clinical Dementia Rating Scale Sum of Boxes score (OR 1.47, p = 0.013) and impaired memory modality (impaired both visual and verbal memories compared with visual only, OR 3.25, p = 0.001). Also, presence of APOE ɛ 4 (OR 4.14, p < 0.001) was associated with PET-Aβ+. These predictors were applied to develop the nomogram, which showed good prediction performance (C-statistics = 0.79). Its prediction performances were 0.77/0.74 in internal/external validation. Conclusions: The nomogram consisting of NP profiles, especially memory domain, and APOE ɛ 4 genotype may provide a useful predictive model of PET-Aβ+ in patients with aMCI. Show more
Keywords: Amnestic mild cognitive impairment, amyloid PET positivity, neuropsychological tests, nomogram, prediction
DOI: 10.3233/JAD-180048
Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 681-691, 2018
Authors: Kim, Seung Joo | Jung, Na-Yeon | Kim, Young Ju | Park, Seong Beom | Kim, KoWoon | Kim, Yeshin | Jang, Hyemin | Kim, Si Eun | Cho, Soo Hyun | Kim, Jun Pyo | Jung, Young Hee | Woo, Sook-Young | Kim, Seon Woo | Lockhart, Samuel N. | Kim, Eun-Joo | Kim, Hee Jin | Lee, Jong-Min | Chin, Juhee | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: Background: Frontal behavioral impairment (FrBI) is commonly observed in various degenerative diseases and refers to various behavioral symptoms. Objective: We investigated the effects of the presence of FrBI on cortical thickness, and the longitudinal neuropsychological changes in people in the predementia stage. Methods: A total of 794 individuals completed neuropsychological tests and the Frontal Behavioral Inventory (FBI) Questionnaire, and underwent magnetic resonance (MR) scanning. Participants were analyzed and grouped into non-FrBI (FBI = 0) or FrBI (FBI≥1). Cortical thickness was measured on MR images using a surface-based method. Results: In total, 281 people with subjective cognitive decline (SCD) and 513 with amnestic …mild cognitive impairment (aMCI) were assessed for FrBI. Relative to people without FrBI, those with FrBI presented reduced cortical thickness in the frontal, anterior temporal and lateral parietal regions (p < 0.05, FDR corrected). People with FrBI developed Alzheimer’s disease, rather than behavioral variant frontotemporal dementia, as observed over seven years. Mixed effects models reported that people with FrBI have greater cognitive decline than those with non-FrBI in multiple domains, including language, memory, and executive functions (p < 0.05, FDR corrected). Furthermore, while negative FrBI symptoms (e.g., deficit behaviors) were associated with greater declines in multiple domains, positive FrBI symptoms (e.g., disinhibition symptoms) were related to declines in visuospatial function and verbal memory. Finally, the occurrence of both types of symptoms correlated with multi-domain cognitive decline. Conclusions: FrBI predicted worse clinical outcomes, including reduced cortical thickness and cognitive decline, which are not necessarily specific to frontal dysfunction. Show more
Keywords: Cognitive decline, cortical thickness, frontotemporal dementia, neuropsychiatric symptoms, neuropsychological tests
DOI: 10.3233/JAD-190007
Citation: Journal of Alzheimer's Disease, vol. 69, no. 1, pp. 213-225, 2019
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: Jang, Hyemin | Ye, Byoung Seok | Woo, Sookyoung | Kim, Sun Woo | Chin, Juhee | Choi, Seong Hye | Jeong, Jee Hyang | Yoon, Soo Jin | Yoon, Bora | Park, Kyung Won | Hong, Yun Jeong | Kim, Hee Jin | Lockhart, Samuel N. | Na, Duk L. | Seo, Sang Won
Article Type: Correction
DOI: 10.3233/JAD-179010
Citation: Journal of Alzheimer's Disease, vol. 61, no. 2, pp. 825-825, 2018
Authors: Jang, Hyemin | Ye, Byoung Seok | Woo, Sookyoung | Kim, Sun Woo | Chin, Juhee | Choi, Seong Hye | Jeong, Jee Hyang | Yoon, Soo Jin | Yoon, Bora | Park, Kyung Won | Hong, Yun Jeong | Kim, Hee Jin | Lockhart, Samuel N. | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: Background: Patients with amnestic mild cognitive impairment (aMCI) have an increased risk of dementia. However, conversion rate varies. Therefore, predicting the dementia conversion in these patients is important. Objective: We aimed to develop a nomogram to predict dementia conversion in aMCI subjects using neuropsychological profiles. Methods: A total of 338 aMCI patients from two hospital-based cohorts were used in analysis. All patients were classified into 1) verbal, visual, or both, 2) early or late, and 3) single or multiple-domain aMCI according to the modality, severity of memory dysfunction, and multiplicity of involved cognitive domains, respectively. Patients were followed up, and …conversion to dementia within 3 years was defined as the primary outcome. Our patients were divided into a training data set and a validation data set. The associations of potential covariates with outcome were tested, and nomogram was constructed by logistic regression model. We also developed another model with APOE data, which included 242 patients. Results: In logistic regression models, both modalities compared with visual only (OR 4.44, 95% CI 1.83–10.75, p = 0.001), late compared to early (OR 2.59, 95% CI 1.17–5.72, p = 0.019), and multiple compared to single domain (OR 3.51, 95% CI 1.62–7.60, p = 0.002) aMCI were significantly associated with dementia conversion within 3 years. A nomogram incorporating these clinical variables was constructed on the training data set and validated on the validation data set. Both nomograms with and without APOE data showed good prediction performance (c-statistics ≥ 0.75). Conclusions: This study showed that several neuropsychological profiles of aMCI are significantly associated with imminent dementia conversion, and a nomogram incorporating these clinical subtypes is simple and useful to help to predict disease progression. Show more
Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, nomogram, prediction model
DOI: 10.3233/JAD-170507
Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1579-1587, 2017
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
The Heterogeneity and Natural History of Mild Cognitive Impairment of Visual Memory Predominant Type
Authors: Ye, Byoung Seok | Chin, Juhee | Kim, Seong Yoon | Lee, Jung-Sun | Kim, Eun-Joo | Lee, Yunhwan | Hong, Chang Hyung | Choi, Seong Hye | Park, Kyung Won | Ku, Bon D. | Moon, So Young | Kim, SangYun | Han, Seol-Hee | Lee, Jae-Hong | Cheong, Hae-Kwan | Park, Sun Ah | Jeong, Jee Hyang | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: We evaluate the longitudinal outcomes of amnestic mild cognitive impairment (aMCI) according to the modality of memory impairment involved. We recruited 788 aMCI patients and followed them up. aMCI patients were categorized into three groups according to the modality of memory impairment: Visual-aMCI, only visual memory impaired; Verbal-aMCI, only verbal memory impaired; and Both-aMCI, both visual and verbal memory impaired. Each aMCI group was further categorized according to the presence or absence of recognition failure. Risk of progression to dementia was compared with pooled logistic regression analyses while controlling for age, gender, education, and interval from baseline. Of the sample, …219 (27.8%) aMCI patients progressed to dementia. Compared to the Visual-aMCI group, Verbal-aMCI (OR = 1.98, 95% CI = 1.19–3.28, p = 0.009) and Both-aMCI (OR = 3.05, 95% CI = 1.97–4.71, p < 0.001) groups exhibited higher risks of progression to dementia. Memory recognition failure was associated with increased risk of progression to dementia only in the Visual-aMCI group, but not in the Verbal-aMCI and Both-aMCI groups. The Visual-aMCI without recognition failure group were subcategorized into aMCI with depression, small vessel disease, or accelerated aging, and these subgroups showed a variety of progression rates. Our findings underlined the importance of heterogeneous longitudinal outcomes of aMCI, especially Visual-aMCI, for designing and interpreting future treatment trials in aMCI. Show more
Keywords: Alzheimer's disease, amnesia, mild cognitive impairment, neuropsychology
DOI: 10.3233/JAD-140318
Citation: Journal of Alzheimer's Disease, vol. 43, no. 1, pp. 143-152, 2015