Comparison of Diagnostic Performances Between Cerebrospinal Fluid Biomarkers and Amyloid PET in a Clinical Setting

Article type: Research Article

Authors: Jung, Na-Yeon^{a; b; 1} | Kim, Eun Soo^{c; 1} | Kim, Hyang-Sook^b | Jeon, Sumin^d | Lee, Myung Jun^d | Pak, Kyoungjune^e | Lee, Jae-Hyeok^{a; b} | Lee, Young Min^f | Lee, Kangyoon^f | Shin, Jin-Hong^{a; b} | Ko, Jun Kyeung^g | Lee, Jae Meen^g | Yoon, Jin A.^h | Hwang, Chungsuⁱ | Choi, Kyung-Unⁱ | Lee, Eun Chong^j | Seong, Joon-Kyung^j | Huh, Gi Yeong^k | Kim, Dae-Seong^{a; b} | Kim, Eun-Joo^{d; *}

Affiliations: [a] Department of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea | [b] Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea | [c] Department of Anesthesia and Pain Medicine, Pusan National University Hospital, School of Medicine, Pusan National University, Busan, Republic of Korea | [d] Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, Republic of Korea | [e] Department of Nuclear Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea | [f] Department of Psychiatry, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea | [g] Department of Neurosurgery, Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea | [h] Department of Rehabilitation Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea | [i] Department of Pathology, Pusan National University School of Medicine, Yangsan, Republic of Korea | [j] School of Biomedical Engineering, Korea University, Seoul, Republic of Korea | [k] Department of Forensic Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea

Correspondence: [*] Correspondence to: Eun-Joo Kim, MD, Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, 179 Gudeok-ro, Seo-gu, Busan, 49241, Korea. Tel.: +82 51 240 7717; Fax: +82 51 245 2783; E-mail: [email protected].

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

Abstract:  The diagnostic performances of cerebrospinal fluid (CSF) biomarkers and amyloid positron emission tomography (PET) were compared by examining the association and concordance or discordance between CSF Aβ1-42 and amyloid PET, after determining our own cut-off values for CSF Alzheimer’s disease (AD) biomarkers. Furthermore, we evaluated the ability of CSF biomarkers and amyloid PET to predict clinical progression. CSF Aβ1-42, t-tau, and p-tau levels were analyzed in 203 individuals [27 normal controls, 38 mild cognitive impairment (MCI), 62 AD dementia, and 76 patients with other neurodegenerative diseases] consecutively recruited from two dementia clinics. We used both visual and standardized uptake value ratio (SUVR)-based amyloid PET assessments for analyses. The association of CSF biomarkers with amyloid PET SUVR, hippocampal atrophy, and cognitive function were investigated by linear regression analysis, and the risk of conversion from MCI to AD dementia was assessed using a Cox proportional hazards model. CSF p-tau/Aβ1-42 and t-tau/Aβ1-42 exhibited the best diagnostic accuracies among the CSF AD biomarkers examined. Correlations were observed between CSF biomarkers and global SUVR, hippocampal volume, and cognitive function. Overall concordance and discordance between CSF Aβ1-42 and amyloid PET was 77% and 23%, respectively. Baseline positive CSF Aβ1-42 for MCI demonstrated a 5.6-fold greater conversion risk than negative CSF Aβ1-42 .  However, amyloid PET findings failed to exhibit significant prognostic value. Therefore, despite presence of a significant correlation between the CSF Aβ1-42 level and SUVR of amyloid PET, and a relevant concordance between CSF Aβ1-42 and amyloid PET, baseline CSF Aβ1-42 better predicted AD conversion.

Keywords: Alzheimer disease, amyloid, cerebrospinal fluid, mild cognitive impairment, positron emission tomography, tau

DOI: 10.3233/JAD-191109

Journal: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 473-490, 2020