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Association of β-Amyloid and Basal Forebrain With Cortical Thickness and Cognition in Alzheimer and Lewy Body Disease Spectra

 Han Soo Yoo  ;  Seun Jeon  ;  Enrica Cavedo  ;  MinJin Ko  ;  Mijin Yun  ;  Phil Hyu Lee  ;  Young H Sohn  ;  Michel J Grothe  ;  Stefan Teipel  ;  Harald Hampel  ;  Alan C Evans  ;  Byoung Seok Ye 
 NEUROLOGY, Vol.98(9) : e947-e957, 2022-03 
Journal Title
Issue Date
Alzheimer Disease* / complications ; Alzheimer Disease* / diagnostic imaging ; Amyloid beta-Peptides / metabolism ; Basal Forebrain* / metabolism ; Brain / metabolism ; Cognition ; Cognitive Dysfunction* ; Cross-Sectional Studies ; Humans ; Lewy Body Disease* / complications ; Lewy Body Disease* / diagnostic imaging ; Positron-Emission Tomography
Objective: Cholinergic degeneration and β-amyloid contribute to brain atrophy and cognitive dysfunction in Alzheimer disease (AD) and Lewy body disease (LBD), but their relationship has not been comparatively evaluated.

Methods: In this cross-sectional study, we recruited 28 normal controls (NC), 55 patients with AD mild cognitive impairment (MCI), 34 patients with AD dementia, 28 patients with LBD MCI, and 51 patients with LBD dementia. Participants underwent cognitive evaluation, brain MRI to measure the basal forebrain (BF) volume and global cortical thickness (CTh), and 18F-florbetaben (FBB) PET to measure the standardized uptake value ratio (SUVR). Using general linear models and path analyses, we evaluated the association of FBB-SUVR and BF volume with CTh or cognitive dysfunction in the AD spectrum (AD and NC) and LBD spectrum (LBD and NC), respectively. Covariates included age, sex, education, deep and periventricular white matter hyperintensities, intracranial volume, hypertension, diabetes, and hyperlipidemia.

Results: BF volume mediated the association between FBB-SUVR and CTh in both the AD and LBD spectra, while FBB-SUVR was associated with CTh independently of BF volume only in the LBD spectrum. Significant correlation between voxel-wise FBB-SUVR and CTh was observed only in the LBD group. FBB-SUVR was independently associated with widespread cognitive dysfunction in both the AD and LBD spectra, especially in the memory domain (standardized beta [B] for AD spectrum = -0.60, B for LBD spectrum = -0.33). In the AD spectrum, BF volume was associated with memory dysfunction (B = 0.18), and CTh was associated with language (B = 0.21) and executive (B = 0.23) dysfunction. In the LBD spectrum, however, BF volume and CTh were independently associated with widespread cognitive dysfunction.

Conclusions: There is a common β-amyloid-related degenerative mechanism with or without the mediation of BF in the AD and LBD spectra, while the association of BF atrophy with cognitive dysfunction is more profound and there is localized β-amyloid-cortical atrophy interaction in the LBD spectrum.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Ye, Byoung Seok(예병석) ORCID logo https://orcid.org/0000-0003-0187-8440
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Jeon, Seun(전세운) ORCID logo https://orcid.org/0000-0003-2817-3352
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