Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories

Hee Jin Kim, Jin Ju Yang, Hunki Kwon, Changsoo Kim, Jong Min Lee, Phillip Chun, Yeo Jin Kim, Na Yeon Jung, Juhee Chin, Seonwoo Kim, Sook Young Woo, Yearn Seong Choe, Kyung Han Lee, Sung Tae Kim, Jae Seung Kim, Jae Hong Lee, Michael W. Weiner, Duk L. Na, Sang Won Seo

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

See Cohen (doi:10.1093/aww183) for a scientific commentary on this article. Amyloid-β and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-β and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-β and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized β = -0.79, P < 0.001; visual memory test, unstandardized β = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized β = -0.05, P = 0.002; Stroop colour test, unstandardized β = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized β = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized β = 0.21, P = 0.010) and time-varying nodal efficiency (standardized β = 0.17, P = 0.024). Time-varying lacune number (standardized β = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized β = 0.17, P = 0.021). Finally, time-varying lacune number (β = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized β = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-β and lacunes have distinct paths, and that amyloid-β or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-β and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.

Original languageEnglish
Pages (from-to)2516-2527
Number of pages12
JournalBrain
Volume139
Issue number9
DOIs
Publication statusPublished - 2016 Sep 1

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Amyloid
Cerebral Small Vessel Diseases
Stroop Test
Executive Function
Color
Multimodal Imaging
Efficiency
Diffusion Tensor Imaging
Neuropsychological Tests
Positron-Emission Tomography
Blood Vessels
Cognitive Dysfunction
Magnetic Resonance Imaging
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Brain

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Kim, H. J., Yang, J. J., Kwon, H., Kim, C., Lee, J. M., Chun, P., ... Seo, S. W. (2016). Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories. Brain, 139(9), 2516-2527. https://doi.org/10.1093/brain/aww148
Kim, Hee Jin ; Yang, Jin Ju ; Kwon, Hunki ; Kim, Changsoo ; Lee, Jong Min ; Chun, Phillip ; Kim, Yeo Jin ; Jung, Na Yeon ; Chin, Juhee ; Kim, Seonwoo ; Woo, Sook Young ; Choe, Yearn Seong ; Lee, Kyung Han ; Kim, Sung Tae ; Kim, Jae Seung ; Lee, Jae Hong ; Weiner, Michael W. ; Na, Duk L. ; Seo, Sang Won. / Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories. In: Brain. 2016 ; Vol. 139, No. 9. pp. 2516-2527.
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abstract = "See Cohen (doi:10.1093/aww183) for a scientific commentary on this article. Amyloid-β and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-β and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-β and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized β = -0.79, P < 0.001; visual memory test, unstandardized β = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized β = -0.05, P = 0.002; Stroop colour test, unstandardized β = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized β = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized β = 0.21, P = 0.010) and time-varying nodal efficiency (standardized β = 0.17, P = 0.024). Time-varying lacune number (standardized β = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized β = 0.17, P = 0.021). Finally, time-varying lacune number (β = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized β = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-β and lacunes have distinct paths, and that amyloid-β or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-β and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.",
author = "Kim, {Hee Jin} and Yang, {Jin Ju} and Hunki Kwon and Changsoo Kim and Lee, {Jong Min} and Phillip Chun and Kim, {Yeo Jin} and Jung, {Na Yeon} and Juhee Chin and Seonwoo Kim and Woo, {Sook Young} and Choe, {Yearn Seong} and Lee, {Kyung Han} and Kim, {Sung Tae} and Kim, {Jae Seung} and Lee, {Jae Hong} and Weiner, {Michael W.} and Na, {Duk L.} and Seo, {Sang Won}",
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Kim, HJ, Yang, JJ, Kwon, H, Kim, C, Lee, JM, Chun, P, Kim, YJ, Jung, NY, Chin, J, Kim, S, Woo, SY, Choe, YS, Lee, KH, Kim, ST, Kim, JS, Lee, JH, Weiner, MW, Na, DL & Seo, SW 2016, 'Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories', Brain, vol. 139, no. 9, pp. 2516-2527. https://doi.org/10.1093/brain/aww148

Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories. / Kim, Hee Jin; Yang, Jin Ju; Kwon, Hunki; Kim, Changsoo; Lee, Jong Min; Chun, Phillip; Kim, Yeo Jin; Jung, Na Yeon; Chin, Juhee; Kim, Seonwoo; Woo, Sook Young; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Weiner, Michael W.; Na, Duk L.; Seo, Sang Won.

In: Brain, Vol. 139, No. 9, 01.09.2016, p. 2516-2527.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories

AU - Kim, Hee Jin

AU - Yang, Jin Ju

AU - Kwon, Hunki

AU - Kim, Changsoo

AU - Lee, Jong Min

AU - Chun, Phillip

AU - Kim, Yeo Jin

AU - Jung, Na Yeon

AU - Chin, Juhee

AU - Kim, Seonwoo

AU - Woo, Sook Young

AU - Choe, Yearn Seong

AU - Lee, Kyung Han

AU - Kim, Sung Tae

AU - Kim, Jae Seung

AU - Lee, Jae Hong

AU - Weiner, Michael W.

AU - Na, Duk L.

AU - Seo, Sang Won

PY - 2016/9/1

Y1 - 2016/9/1

N2 - See Cohen (doi:10.1093/aww183) for a scientific commentary on this article. Amyloid-β and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-β and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-β and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized β = -0.79, P < 0.001; visual memory test, unstandardized β = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized β = -0.05, P = 0.002; Stroop colour test, unstandardized β = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized β = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized β = 0.21, P = 0.010) and time-varying nodal efficiency (standardized β = 0.17, P = 0.024). Time-varying lacune number (standardized β = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized β = 0.17, P = 0.021). Finally, time-varying lacune number (β = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized β = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-β and lacunes have distinct paths, and that amyloid-β or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-β and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.

AB - See Cohen (doi:10.1093/aww183) for a scientific commentary on this article. Amyloid-β and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-β and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-β and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized β = -0.79, P < 0.001; visual memory test, unstandardized β = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized β = -0.05, P = 0.002; Stroop colour test, unstandardized β = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized β = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized β = 0.21, P = 0.010) and time-varying nodal efficiency (standardized β = 0.17, P = 0.024). Time-varying lacune number (standardized β = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized β = 0.17, P = 0.021). Finally, time-varying lacune number (β = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized β = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-β and lacunes have distinct paths, and that amyloid-β or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-β and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.

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