Metabolic Asymmetry Relates to Clinical Characteristics and Brain Network Abnormalities in Alzheimer’s Disease

Article type: Research Article

Authors: Lin, Huamei^{a; b; 1} | Pan, Tingting^{c; 1} | Wang, Min^{d; 1} | Ge, Jingjie^{a; b} | Lu, Jiaying^{a; b} | Ju, Zizhao^{a; b} | Chen, Keliang^{b; e} | Zhang, Huiwei^{a; b} | Guan, Yihui^{a; b} | Zhao, Qianhua^{b; e} | Shan, Baoci^c | Nie, Binbin^{c; 2; *} | Zuo, Chuantao^{a; b; 2; *} | Wu, Ping^{a; b; 2; *}

Affiliations: [a] Deparment of Nuclear Medicine / PET Center, Huashan Hospital, Fudan University, Shanghai, China | [b] National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China | [c] Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High EnergyPhysics, Chinese Academy of Sciences, Beijing, China | [d] Institute of Biomedical Engineering, School of Communication and Information Engineering, Shanghai University, Shanghai, China | [e] Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Ping Wu, Huashan Hospital, Fudan University, No. 518 East Wuzhong Road, Shanghai, China. Tel.: +86 021 64283265; E-mail: wupingpet@fudan.edu.cn; ORCID: 0000-0002-2758-1218 and Chuantao Zuo, Huashan Hospital, Fudan University, No. 518 East Wuzhong Road, Shanghai, China. Tel.: +86 021 64283265; E-mail: zuochuantao2000@126.com; ORCID: 0000-0002-8856-7217 and Binbin Nie, Chinese Academy of Sciences, 19B Yuquan Road, Shijingshan Distinct, Beijing, China. Tel.: +1 86 010 88236872; E-mail: niebb@ihep.ac.cn.

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

Note: [2] Equally-contributed senior authors

Abstract: Background:Metabolic asymmetry has been observed in Alzheimer’s disease (AD), but different studies have inconsistent viewpoints. Objective:To analyze the asymmetry of cerebral glucose metabolism in AD and investigate its clinical significance and potential metabolic network abnormalities. Methods:Standardized uptake value ratios (SUVRs) were obtained from 18F-FDG positron emission tomography (PET) images of all participants, and the asymmetry indices (AIs) were calculated according to the SUVRs. AD group was divided into left/right-dominant or bilateral symmetric hypometabolism (AD-L/AD-R or AD-BI) when more than half of the AIs of the 20 regions of interest (ROIs) were < –2SD, >2SD, or between±1SD. Differences in clinical features among the three AD groups were compared, and the abnormal network characteristics underlying metabolic asymmetry were explored. Results:In AD group, the proportions of AD-L, AD-R, and AD-BI were 28.4%, 17.9%, and 18.5%, respectively. AD-L/AD-R groups had younger age of onset and faster rate of cognitive decline than AD-BI group (p < 0.05). The absolute values of AIs in half of the 20 ROIs became higher at follow-up than at baseline (p < 0.05). Compared with those in AD-BI group, metabolic connection strength of network, global efficiency, cluster coefficient, degree centrality and local efficiency were lower, but shortest path length was longer in AD-L and AD-R groups (p < 0.05). Conclusion:Asymmetric and symmetric hypometabolism may represent different clinical subtypes of AD, which may provide a clue for future studies on the heterogeneity of AD and help to optimize the design of clinical trials.

Keywords: Alzheimer’s disease, cerebral glucose hypometabolism, graph theory, metabolic asymmetry, metabolic connectivity, Mini-Mental State Examination

DOI: 10.3233/JAD-221258

Journal: Journal of Alzheimer's Disease, vol. 93, no. 4, pp. 1395-1406, 2023