Perivascular Space Predicts Brain Hypometabolism of Individuals with Underlying Amyloid Pathology

Article type: Research Article

Authors: Shi, Xiaolei^{a; b; *} | Zhou, Nan^{b; c} | Sun, Bin^{b; c} | Wu, Yongshun^d | Hu, Yachun^{b; e} | Ning, Yuping^{a; b; f; *} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China | [b] Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China | [c] The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China | [d] The Department of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China | [e] Department of Neurology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China | [f] The First School of Clinical Medicine, Southern Medical University, Guangzhou, China

Correspondence: [*] Correspondence to: Yuping Ning, Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders; The First School of Clinical Medicine, Southern Medical University, Guangzhou, China. E-mail: ningjeny@126.com and Xiaolei Shi, Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China. E-mail:shixl@gzhmu.edu.cn.

Note: [1] Data used in this article were obtained from the ADNI database (http://adni.loni.usc.edu), which is easily available for download from the Laboratory of Neuroimaging (LONI) website to the research public. As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how-to-apply/ADNI-Acknowledgement-List.pdf

Abstract: Background:Reduced signal on fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valid proxy for neurodegeneration in Alzheimer’s disease (AD). Perivascular space (PVS) is believed to be associated with AD pathology and cognitive decline. Objective:This study aimed to investigate the associations of PVS with FDG-PET and cognitive performance based on the burden of amyloid pathology. Methods:We used magnetic resonance imaging (MRI) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). MRI-visible PVS in basal ganglia (BG) and centrum semi-oval (CSO) were visually classified as: none/mild, moderate or frequent/severe. The association of PVS with brain FDG-PET was explored based on the burden of amyloid pathology, where a cerebrospinal fluid (CSF) t-tau/Aβ42 with the ratio≥0.27 was defined as high amyloid pathology. Moreover, the relationships between PVS and cognitive performance variables (ADNI-MEM and ADNI-EF) were studied. Results:For participants with higher tau/Aβ42 ratio, CSO-PVS severity was independently associated with lower FDG-PET. There were significant interaction effects between moderate or frequent/severe CSO-PVS and time on FDG decline in people with high amyloid pathology. The interaction between CSO-PVS and time (follow-up) was consistently associated with ADNI-MEM and ADNI-EF decline in individuals with high amyloid pathology. Conclusion:The study established the differential utility of PVS in BG and CSO for predicting brain metabolism. These findings suggest that CSO-PVS serves as a contributing factor to brain metabolism and cognitive decline associated with amyloid pathology.

Keywords: Amyloid, basal ganglia, centrum semi-oval, metabolism, perivascular space

DOI: 10.3233/JAD-220426

Journal: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1329-1337, 2022