Association of Basal Forebrain Volume with Amyloid, Tau, and Cognition in Alzheimer’s Disease

Article type: Research Article

Authors: Yoo, Han Soo^a | Kim, Han-Kyeol^a | Lee, Jae-Hoon^b | Chun, Joong-Hyun^c | Lee, Hye Sun^d | Grothe, Michel J.^e | Teipel, Stefan^{f; g} | Cavedo, Enrica^h | Vergallo, Andrea^h | Hampel, Harald^h | Ryu, Young Hoon^b | Cho, Hanna^{a; *; 1} | Lyoo, Chul Hyoung^{a; *; 1}

Affiliations: [a] Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea | [b] Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea | [c] Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea | [d] Department of Biostatistics, Yonsei University College of Medicine, Seoul, Republic of Korea | [e] Reina Sofia Alzheimer Center, CIEN Foundation-ISCIII, Madrid, Spain | [f] Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)-Rostock/Greifswald, Rostock, Germany | [f] Department of Psychosomatic Medicine, University Medicine Rostock, Germany | [h] Sorbonne University Alzheimer Precision Medicine, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

Correspondence: [*] Correspondence to: Chul Hyoung Lyoo, MD, PhD, Professor, Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, 20 Eonjuro 63-gil, Gangnam-gu, Seoul, South Korea. Tel.:+82 2 2019 3326; Fax:+82 2 3462 5904; E-mail: [email protected] and Hanna Cho, MD, PhD, Associate Professor, Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, 20 Eonjuro 63-gil, Gangnam-gu, Seoul, South Korea. Tel.:+82 2 2019 3327; Fax:+82 2 3462 5904; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer’s disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. Objective:To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. Methods:In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [Aβ]-negative cognitively unimpaired, 6 Aβ-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, 18F-florbetaben PET for Aβ, 18F-flortaucipir PET for tau, and detailed cognitive testing longitudinally. We investigated the baseline and longitudinal association of BF volume with Aβ and tau standardized uptake value ratio and cognition. Results:Cross-sectionally, lower BF volume was not independently associated with higher cortical Aβ, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster Aβ accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline Aβ and tau burden. Conclusions:Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function.

Keywords: Alzheimer’s disease, amyloid-beta, basal forebrain, cognition, tau

DOI: 10.3233/JAD-230975

Journal: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 145-159, 2024