Authors: Lee, Wha Jin | Han, Cheol E. | Aganj, Iman | Seo, Sang Won | Seong, Joon-Kyung
Article Type: Research Article
Abstract: Recent advances in neuroimaging technology have shown that rich club organization in human brain networks plays a crucial role in global communication and cognitive functionality. In this study, we investigated rich club organization within white matter structural brain networks in two common types of dementia, Alzheimer’s disease (AD) and subcortical vascular dementia (SVaD). We recruited 30 AD patients ([11C] Pittsburgh compound-B (PiB) PET positive), 39 SVaD patients (PiB negative), and 72 age-, gender-, and education-matched cognitively normal (CN) subjects. Rich club organization was significantly disrupted in both dementia patient groups, which exhibited higher rich club coefficients than the CN group. …Rich club organization in the patient groups was primarily disrupted over the left frontal and left middle temporal areas when compared to the CN group. The number of rich club nodes was significantly reduced in the dementia groups, which was more severe in SVaD (p = 0.0107, permutation-based t -test). Although rich club organization was disrupted both in the patient groups, its disruption pattern is different between them. The rich-club connections normalized by degree-and-strength preserved random networks were significantly increased in the dementia groups with SVaD more severely, and feeder connections were reduced more significantly than in AD. Furthermore, SVaD patients exhibited more sporadic disruption in white matter connectivity than AD patients, with local connections showing a more significant degree of deterioration. Combined with the distinct disruption in rich club nodes, these findings may imply a differing role for rich club organization in AD and SVaD, due to different pathological mechanisms. Show more
Keywords: Alzheimer’s disease, diffusion tensor imaging, diffusion tractography, subcortical vascular dementia
DOI: 10.3233/JAD-180027
Citation: Journal of Alzheimer's Disease, vol. 63, no. 3, pp. 977-987, 2018
Authors: Kim, Jinhee | Jang, Hyemin | Park, Yu-hyun | Youn, Jinyoung | Seo, Sang Won | Kim, Hee Jin | Na, Duk L.
Article Type: Research Article
Abstract: Background: Age at onset was suggested as one possible risk factor for motor dysfunction in Alzheimer’s disease (AD). Objective: We investigated the association of motor symptoms with cognition or neurodegeneration in patients with AD, and whether this association differs by the age at onset. Methods: We included 113 amyloid positive AD patients and divided them into early-onset AD (EOAD) and late-onset AD (LOAD), who underwent the Unified Parkinson’s Disease Rating Scale (UPDRS)-Part III (=UPDRS) scoring, Mini-Mental State Examination (MMSE)/Clinical Deterioration Rating Sum-of-Boxes (CDR-SOB), and magnetic resonance image (MRI). Multiple linear regression was used to evaluate the association of UPDRS and …MMSE/CDR-SOB or MRI neurodegeneration measures, and whether the association differs according to the group. Results: The prevalence of motor symptoms and their severity did not differ between the groups. Lower MMSE (β= –1.1, p < 0.001) and higher CDR-SOB (β= 2.0, p < 0.001) were significantly associated with higher UPDRS. There was no interaction effect between MMSE/CDR-SOB and AD group on UPDRS. Global or all regional cortical thickness and putaminal volume were negatively associated with UPDRS score, but the interaction effect of neurodegeneration and AD group on UPDRS score was significant only in parietal lobe (p for interaction = 0.035), which showed EOAD to have a more pronounced association between parietal thinning and motor symptoms. Conclusion: Our study suggested that the severity of motor deterioration in AD is related to the severity of cognitive impairment itself rather than age at onset, and motor symptoms might occur through multiple mechanisms including cortical and subcortical atrophy. Show more
Keywords: Alzheimer’s disease, neuropsychological tests, parkinsonian disorders
DOI: 10.3233/JAD-220745
Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 345-354, 2023
Authors: Moon, Hasom | Ham, Hongki | Yun, Jihwan | Shin, Daeun | Lee, Eun Hye | Kim, Hee Jin | Seo, Sang Won | Na, Duk L. | Jang, Hyemin
Article Type: Research Article
Abstract: Background: Amyloid-β (Aβ) commonly coexists and impacts prognosis in subcortical vascular cognitive impairment (SVCI). Objective: This study aimed to examine the differences in clinical and neuroimaging variables between Aβ-positive and Aβ-negative SVCI and to propose a prediction model for Aβ positivity in clinically diagnosed SVCI patients. Methods: A total of 130 patients with SVCI were included in model development, and a separate cohort of 70 SVCI patients was used in external validation. The variables for the prediction model were selected by comparing the characteristics of the Aβ-negative and Aβ-positive SVCI groups. The final model was determined using a stepwise method. …The model performance was evaluated using the receiver operating characteristic (ROC) curve and a calibration curve. A nomogram was used for visualization. Results: Among 130 SVCI patients, 70 (53.8%) were Aβ-positive. The Aβ-positive SVCI group was characterized by older age, tendency to be in the dementia stage, a higher prevalence of APOE ɛ 4, a lower prevalence of lacune, and more severe medial temporal atrophy (MTA). The final prediction model, which excluded MTA grade following the stepwise method for variable selection, demonstrated good accuracy in distinguishing between Aβ-positive and Aβ-negative SVCI, with an area under the curve (AUC) of 0.80. The external validation demonstrated an AUC of 0.71. Conclusions: The findings suggest that older age, dementia stage, APOE ɛ 4 carrier, and absence of lacunes may be predictive of Aβ positivity in clinically diagnosed SVCI patients. Show more
Keywords: Alzheimer’s disease, amyloid-β, dementia, mild cognitive impairment, subcortical vascular cognitive impairment
DOI: 10.3233/JAD-240196
Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1117-1127, 2024
Authors: Jang, Hyemin | Park, Yu-hyun | Choe, Young Sim | Kang, Sung Hoon | Kang, Eun-Sook | Lee, Seunghoon | Seo, Sang Won | Kim, Hee Jin | Na, Duk L.
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) and normal pressure hydrocephalus (NPH) commonly coexist. Objective: We aimed to characterize an overlapping syndrome of AD and NPH that presents with gait disturbance, ventriculomegaly on magnetic resonance imaging, and significant amyloid deposition on positron emission tomography (PET). Methods: Of 114 patients who underwent cerebrospinal fluid (CSF) drainage for a possible diagnosis of NPH between 2015 and 2020 in Samsung Medical Center, we identified 24 patients (21.1%) with the NPH patients with amyloid deposition on PET, which we referred to as hydrocephalic AD in this study. We compared their clinical and imaging findings with those of …123 typical AD without hydrocephalic signs/symptoms. We also investigated the frequency and potential predictors of the tap test response in hydrocephalic AD. Results: Evans’ index was 0.36±0.03, and a disproportionately enlarged subarachnoid space was present in 54.2% of the hydrocephalic AD patients. The mean age (75.2±7.3 years) and the APOE4 frequency (68.2%) did not differ from those of AD controls. However, the hydrocephalic AD patients showed better memory and language performance, and a thinner cingulate cortex. About 42% of the hydrocephalic AD patients responded to the tap test, of whom seven underwent shunt surgery. Cognition did not improve, whereas gait improved after shunt surgery in all. Conclusion: Hydrocephalic AD has different neuropsychological and imaging characteristics from typical AD. Future studies are warranted to further investigate the effect of CSF removal on their clinical course and to elucidate the pathophysiological interaction between amyloid and NPH. Show more
Keywords: Alzheimer’s disease, cerebrospinal fluid, hydrocephalus, MRI, PET
DOI: 10.3233/JAD-215110
Citation: Journal of Alzheimer's Disease, vol. 85, no. 4, pp. 1467-1479, 2022
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
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, Yeshin | Jang, Hyemin | Kim, Seung Joo | Cho, Soo Hyun | Kim, Si Eun | Kim, Sung Tae | Kim, Hee Jin | Moon, Seung Hwan | Ewers, Michael | Im, Kiho | Kwon, Hunki | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: Late life depression is related to pathologic burdens, such as cerebral small vascular disease (CSVD) and amyloid, which are associated with brain network changes and cortical thinning. To examine the associations of various CSVD imaging markers, amyloid, and network changes with depression in cognitively impaired patients, we prospectively recruited 228 cognitively impaired patients having various degrees of amyloid and CSVD who underwent diffuse tensor image and PiB PET. Greater CSVD burden was associated with greater Geriatric Depression Scale (GDS) (white matter hyperintensities, WMH: p = 0.025, lacunes: p < 0.001) but not with amyloid (p = 0.095), and cortical thinning (p = 0.630) was …not associated with greater GDS. The changes in white matter networks were related to GDS with decreasing integration (global efficiency: p < 0.001) and increasing segregation (clustering coefficient: p = 0.009). The network changes mediated the relationships of WMH and lacunes with GDS. Our findings provide insight to better understand how CSVD burdens contribute to depression in cognitively impaired patients having varying degrees of amyloid and vascular burdens. Show more
Keywords: Depression, network, small vessel disease
DOI: 10.3233/JAD-180394
Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 597-605, 2018
Authors: Lee, Jin San | Kim, Seonwoo | Yoo, Heejin | Park, Seongbeom | Jang, Young Kyoung | Kim, Hee Jin | Kim, Ko Woon | Kim, Yeshin | Jang, Hyemin | Park, Key-Chung | Yaffe, Kristine | Yang, Jin-Ju | Lee, Jong-Min | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: Background/Objective: In this study, we investigated a long-term trajectory of brain aging (from the 20 s to over-80) in cognitively normal (CN) individuals. We further determined whether differences in sex, education years, and apolipoprotein E ε 4 status affect age-related cortical thinning. Methods: A total of 2,944 CN individuals who underwent high-resolution (3.0-Tesla) magnetic resonance imaging were included in this study. Cortical thickness was measured using a surface-based method. Multiple linear regression analyses were performed to evaluate age-related cortical thinning and related factors. Results: Compared to those in their 20 s/30 s, participants in their 40 s showed thinning primarily …in the medial and lateral frontal and inferior parietal regions, and cortical thinning occurred across most of the cortices with increasing age. Notably, the precuneus, inferior temporal and lateral occipital regions were relatively spared until later in life. Male and lower education years were associated with greater cortical thinning with distinct regional specificity. Conclusion: Our findings provide an important clue to understanding the mechanism of age-related cognitive decline and new strategies for preventing the acceleration of pathological brain aging. Show more
Keywords: Alzheimer’s disease, cognitive disorders, dementia, magnetic resonance imaging
DOI: 10.3233/JAD-170537
Citation: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1237-1246, 2018
Authors: Jang, Hyemin | Kim, Jong Hun | Choi, Seong Hye | Lee, Yunhwan | Hong, Chang Hyung | Jeong, Jee Hyang | Han, Hyun Jeong | Moon, So Young | Park, Kyung Won | Han, Seol-Hee | Park, Kee Hyung | Kim, Hee Jin | Na, Duk L. | Seo, Sang Won
Article Type: Research Article
Abstract: Background: A relationship between body weight, cognitive impairment, and the onset of Alzheimer’s disease (AD) was recently reported. However, to our knowledge, no studies have investigated the relationship between body weight and mortality in Asian AD patients. Objective: We evaluated the relationship between body mass index (BMI) and mortality rate in Korean AD cohorts. Methods: Participants were consecutively included from two Korean representative registries: 579 AD patients from Samsung Medical Center and 1911 AD patients from the Clinical Research Center for Dementia of South Korea study. We combined these two AD cohorts to evaluate the association between BMI and mortality. …BMI was used to categorize the participants into underweight, normal-weight, overweight, and obesity subgroups. All deaths were confirmed through the nationwide mortality database of Statistics Korea. Results: 53 of 181 (29.3%), 208 of 1,127 (18.5%), 88 of 626 (14.1%), and 115 of 556 (20.7%) patients died in the underweight, normal-weight, overweight, and obese subgroups during 43.7 months of follow-up. The time-dependent cox proportional hazards model showed that, relative to the normal-weight subgroup, the underweight group had higher mortality (HR 1.82 (95% CI, 1.07–3.09)) while overweight group had lower mortality rate (HR 0.60 (95% CI, 0.38–0.95)) The effects of underweight and overweight were prominent in younger and older elderly group, respectively. However, there were no interactive effects of dementia severity or gender and BMI on survival rate. Conclusion: Relative to AD patients of normal weight, those who were underweight had an increased mortality rate, and overweight predicted decreased mortality in AD patients. Furthermore, our findings may help facilitate mortality stratification in AD patients by using baseline BMI. Show more
Keywords: Alzheimer’s disease, body mass index, mortality, obesity, survival analysis
DOI: 10.3233/JAD-142790
Citation: Journal of Alzheimer's Disease, vol. 46, no. 2, pp. 399-406, 2015