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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 
 BRAIN, Vol.139(9) : 2516-2527, 2016 
Journal Title
Issue Date
Aged ; Amyloid beta-Peptides/metabolism* ; Aniline Compounds* ; Cerebral Cortex*/diagnostic imaging ; Cerebral Cortex*/metabolism ; Cerebral Cortex*/physiopathology ; Cerebral Small Vessel Diseases*/diagnostic imaging ; Cerebral Small Vessel Diseases*/metabolism ; Cerebral Small Vessel Diseases*/physiopathology ; Cognitive Dysfunction*/diagnostic imaging ; Cognitive Dysfunction*/metabolism ; Cognitive Dysfunction*/physiopathology ; Executive Function/physiology* ; Female ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging/methods* ; Male ; Memory Disorders*/diagnostic imaging ; Memory Disorders*/metabolism ; Memory Disorders*/physiopathology ; Positron-Emission Tomography/methods* ; Stroke, Lacunar/diagnostic imaging ; Stroke, Lacunar/metabolism ; Stroke, Lacunar/physiopathology ; Thiazoles*
amyloid-β ; cerebral small vessel disease ; cognitive trajectory ; downstream imaging markers ; mild cognitive impairment
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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1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Soo(김창수) ORCID logo https://orcid.org/0000-0002-5940-5649
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