Distinctive Mediating Effects of Subcortical Structure Changes on the Relationships Between Amyloid or Vascular Changes and Cognitive Decline

Na-Yeon Jung; Jeong-Hyeon Shin; Hee Jin Kim; Hyemin Jang; Seung Hwan Moon; Seung Joo Kim; Yeshin Kim; Soo Hyun Cho; Ko Woon Kim; Jun Pyo Kim; Young Hee Jung; Sung Tae Kim; Eun-Joo Kim; Duk L Na; Jacob W Vogel; Sangjin Lee; Joon-Kyung Seong; Sang Won Seo

doi:10.3389/fneur.2021.762251

Distinctive Mediating Effects of Subcortical Structure Changes on the Relationships Between Amyloid or Vascular Changes and Cognitive Decline

Front Neurol. 2021 Dec 7:12:762251. doi: 10.3389/fneur.2021.762251. eCollection 2021.

Authors

Na-Yeon Jung¹, Jeong-Hyeon Shin², Hee Jin Kim^{3

4}, Hyemin Jang^{3

4}, Seung Hwan Moon⁵, Seung Joo Kim⁶, Yeshin Kim⁷, Soo Hyun Cho⁸, Ko Woon Kim⁹, Jun Pyo Kim^{3

4}, Young Hee Jung¹⁰, Sung Tae Kim¹¹, Eun-Joo Kim¹², Duk L Na^{3

4}, Jacob W Vogel¹³, Sangjin Lee¹⁴, Joon-Kyung Seong², Sang Won Seo^{3

4}

Affiliations

¹ Department of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Yangsan, South Korea.
² School of Biomedical Engineering, Korea University, Seoul, South Korea.
³ Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁴ Neuroscience Center, Samsung Medical Center, Seoul, South Korea.
⁵ Department of Nuclear Medicine, Samsung Medical Center, Seoul, South Korea.
⁶ Department of Neurology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea.
⁷ Department of Neurology, Kangwon National University College of Medicine, Chuncheon-si, South Korea.
⁸ Department of Neurology, Chonnam National University Medical School and Hospital, Gwangju, South Korea.
⁹ Department of Neurology, Chonbuk National University Medical School and Hospital, Jeonju, South Korea.
¹⁰ Department of Neurology, Myongji Hospital, College of Medicine, Hanyang University, Goyang, South Korea.
¹¹ Department of Radiology, Samsung Medical Center, Seoul, South Korea.
¹² Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine, Pusan, South Korea.
¹³ Montreal Neurological Institute, McGill University, Montrèal, QC, Canada.
¹⁴ Graduate School, Department of Statistics, Pusan National University, Busan, South Korea.

Abstract

Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aβ) and lacune with cognitive function in patients with mild cognitive impairment (MCI). Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB) PET for 3 years. The mediation effect of subcortical structure on the association of PiB or lacunes with cognitive function was analyzed using mixed effects models. Results: Volume changes in the amygdala and hippocampus partially mediated the effect of PiB changes on memory function (direct effect = -0.168/-0.175, indirect effect = -0.081/-0.077 for amygdala/hippocampus) and completely mediated the effect of PiB changes on clinical dementia rating scale sum of the box (CDR-SOB) (indirect effect = 0.082/0.116 for amygdala/hippocampus). Volume changes in the thalamus completely mediated the effect of lacune on memory, frontal executive functions, and CDR-SOB (indirect effect = -0.037, -0.056, and 0.047, respectively). Conclusions: Our findings provide a better understanding of the distinct role of subcortical structures in the mediation of the relationships of amyloid or vascular changes with a decline in specific cognitive domains.

Keywords: amyloid; cognition; lacune; mediation; subcortical structure.