Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer's Disease

Eun-Chong Lee; Jae Myeong Kang; Seongho Seo; Ha-Eun Seo; Sang-Yoon Lee; Kee Hyung Park; Duk L Na; Young Noh; Joon-Kyung Seong

doi:10.3389/fnagi.2020.563559

Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer's Disease

Front Aging Neurosci. 2020 Oct 26:12:563559. doi: 10.3389/fnagi.2020.563559. eCollection 2020.

Authors

Eun-Chong Lee¹, Jae Myeong Kang², Seongho Seo³, Ha-Eun Seo⁴, Sang-Yoon Lee³, Kee Hyung Park⁵, Duk L Na^{6

7}, Young Noh^{5

8}, Joon-Kyung Seong^{1

9}

Affiliations

¹ School of Biomedical Engineering, Korea University, Seoul, South Korea.
² Department of Psychiatry, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea.
³ Department of Neuroscience, College of Medicine, Gachon University, Incheon, South Korea.
⁴ Neuroscience Research Institute, Gachon University, Incheon, South Korea.
⁵ Department of Neurology, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea.
⁶ Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁷ Neuroscience Center, Samsung Medical Center, Seoul, South Korea.
⁸ Department of Health Science and Technology, GAIHST, Gachon University, Incheon, South Korea.
⁹ Department of Artificial Intelligence, Korea University, Seoul, South Korea.

Abstract

The objectives of this study were to compare the topographical subcortical shape and to investigate the effects of tau or amyloid burden on atrophic patterns in early onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). One hundred and sixty-one participants (53 EOAD, 44 LOAD, 33 young controls, and 31 older controls) underwent [18F]THK5351 positron emission tomography (PET), [18F]flutemetamol (FLUTE) PET, and 3T MRI scans. We used surface-based analysis to evaluate subcortical structural shape, permutation-based statistics for group comparisons, and Spearman's correlations to determine associations with THK, FLUTE, cortical thickness, and neuropsychological test results. When compared to their age-matched controls, EOAD patients exhibited shape reduction in the bilateral amygdala, hippocampus, caudate, and putamen, while in LOAD patients, the bilateral amygdala and hippocampus showed decreased shapes. In EOAD, widespread subcortical shrinkage, with less association of the hippocampus, correlated with THK retention and cortical thinning, while in LOAD patients, subcortical structures were limited which had significant correlation with THK or mean cortical thickness. Subcortical structural shape showed less correlation with FLUTE global retention in both EOAD and LOAD. Multiple cognitive domains, except memory function, correlated with the bilateral amygdala, caudate, and putamen in EOAD patients, while more restricted regions in the subcortical structures were correlated with neuropsychological test results in LOAD patients. Subcortical structures were associated with AD hallmarks in EOAD. However, the correlation was limited in LOAD. Moreover, relationship between subcortical structural atrophy and cognitive decline were quite different between EOAD and LOAD. These findings suggest that the effects of Alzheimer's pathologies on subcortical structural changes in EOAD and LOAD and they may have different courses of pathomechanism.

Keywords: Alzheimer’s disease; amyloid; cortical thickness; magnetic resonance imaging; positron emission tomography; subcortical shape analysis; tau.