Association of Subjective Cognitive Decline with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study

Article type: Research Article

Authors: Wen, Chen^a | Bi, Yan-Lin^b | Hu, Hao^a | Huang, Shu-Yi^c | Ma, Ya-Hui^a | Hu, He-Ying^a | Tan, Lan^{a; *} | Yu, Jin-Tai^{c; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [b] Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao University, China | [c] From Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Prof. Jin-Tai Yu, MD, PhD, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: [email protected]; Dr. Lan Tan, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, No.5 Donghai Middle Road, Qingdao, China. E-mail: [email protected].

Abstract: Background: Subjective cognitive decline (SCD) might occur at the early stages of dementia. Individuals with SCD have an increased risk of subsequent objective cognitive decline and greater rates of progression to dementia. Objective: We aimed to explore the associations between SCD and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in cognitively normal individuals. Methods: A total of 1,099 cognitively normal elders with available data on CSF biomarkers of AD pathology (Aβ42, P-tau, and T-tau) were included in our analysis. Linear regression was used to examine the associations of SCD status and SCD severity with CSF biomarkers. Additionally, a review was conducted to discuss the associations between SCD and CSF biomarkers of AD pathology. Results: After adjustments for covariates, SCD and SCD severity showed significant associations with CSF Aβ42 (SCD: β= –0.0003, p = 0.0263; SCD severity: β= –0.0004, p = 0.0046), CSF T-tau/Aβ42 ratio (SCD: β= 0.1080, p = 0.0064; SCD severity: β= 0.1129, p = 0.0009) and CSF P-tau/Aβ42 ratio (SCD: β= 0.0167, p = 0.0103; SCD severity: β= 0.0193, p = 0.0006) rather than T-tau and P-tau compared with cognitively normal individuals. In the review, a total of 28 studies were finally included after reviewing 174 articles. CSF Aβ42 was lower in SCD than cognitively normal (CN) individuals, but higher than those with objective cognitive decline. However, CSF tau pathology showed no difference between SCD and CN. Conclusion: The results indicated that pathophysiological changes in CSF Aβ pathology occurred in individuals with SCD, which provide new insights into early intervention of AD.

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarker, subjective cognitive decline

DOI: 10.3233/JAD-215178

Journal: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1143-1151, 2022