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: Banerjee, Gargi | Jang, Hyemin | Kim, Hee Jin | Kim, Sung Tae | Kim, Jae Seung | Lee, Jae Hong | Im, Kiho | Kwon, Hunki | Lee, Jong Min | Na, Duk L. | Seo, Sang Won | Werring, David John
Article Type: Research Article
Abstract: Background: Recent evidence suggests that combining individual imaging markers of cerebral small vessel disease (SVD) may more accurately reflect its overall burden and better correlate with clinical measures. Objective: We wished to establish the clinical relevance of the total SVD score in a memory clinic population by investigating the association with SVD score and cognitive performance, cortical atrophy, and structural network measures, after adjusting for amyloid-β burden. Methods: We included 243 patients with amnestic mild cognitive impairment (MCI), Alzheimer’s disease dementia, subcortical vascular MCI, or subcortical vascular dementia. All underwent MR and [11 C] PiB-PET scanning and had standardized cognitive …testing. Multiple linear regression was used to evaluate the relationships between SVD score and cognition, cortical thickness, and structural network measures. Path analyses were performed to evaluate whether network disruption mediates the effects of SVD score on cortical thickness and cognition. Results: Total SVD score was associated with the performance of frontal (β – 4.31, SE 2.09, p = 0.040) and visuospatial (β – 0.95, SE 0.44, p = 0.032) tasks, and with reduced cortical thickness in widespread brain regions. Total SVD score was negatively correlated with nodal efficiency, as well as changes in brain network organization, with evidence of reduced integration and increasing segregation. Path analyses showed that the associations between SVD score and frontal and visuospatial scores were partially mediated by decreases in their corresponding nodal efficiency and cortical thickness. Conclusion: Total SVD burden has clinical relevance in a memory clinic population and correlates with cognition, and cortical atrophy, as well as structural network disruption. Show more
Keywords: Alzheimer’s disease, cerebral small vessel diseases, cognitive dysfunction, magnetic resonance imaging, positron-emission tomography, vascular dementia
DOI: 10.3233/JAD-170943
Citation: Journal of Alzheimer's Disease, vol. 63, no. 4, pp. 1485-1497, 2018
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