Associations between cerebrospinal fluid markers and cognition in ageing and dementia: A systematic review

• Published in: The European journal of neuroscience Vol. 56; no. 9; pp. 5650 - 5713
• Main Authors: Saunders, Tyler S., Gadd, Danni A., Spires‐Jones, Tara L., King, Declan, Ritchie, Craig, Muniz‐Terrera, Graciela
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.11.2022; John Wiley and Sons Inc
• Subjects: Aging; Alzheimer disease; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Clinical trials; Cognition; Cognition & reasoning; Cognitive ability; cognitive aging; Cognitive Dysfunction - diagnosis; Dementia; Dementia disorders; Frontotemporal dementia; Humans; Neurodegenerative diseases; Neurogranin; Pentraxins; Reviews; Special Issue Review; Standardization; Systematic review; tau Proteins - cerebrospinal fluid; dementia; cognition; Alzheimer disease; biomarkers; cerebrospinal fluid; cognitive aging
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.15656

A biomarker associated with cognition in neurodegenerative dementias would aid in the early detection of disease progression, complement clinical staging and act as a surrogate endpoint in clinical trials. The current systematic review evaluates the association between cerebrospinal fluid protein markers of synapse loss and neuronal injury and cognition. We performed a systematic search which revealed 67 studies reporting an association between cerebrospinal fluid markers of interest and neuropsychological performance. Despite the substantial heterogeneity between studies, we found some evidence for an association between neurofilament‐light and worse cognition in Alzheimer's diseases, frontotemporal dementia and typical cognitive ageing. Moreover, there was an association between cerebrospinal fluid neurogranin and cognition in those with an Alzheimer's‐like cerebrospinal fluid biomarker profile. Some evidence was found for cerebrospinal fluid neuronal pentraxin‐2 as a correlate of cognition across dementia syndromes. Due to the substantial heterogeneity of the field, no firm conclusions can be drawn from this review. Future research should focus on improving standardization and reporting as well as establishing the importance of novel markers such as neuronal pentraxin‐2 and whether such markers can predict longitudinal cognitive decline. We conducted a systematic review of studies examining the association between cerebrospinal fluid markers and neuropsychological performance. Despite substantial heterogeneity in the field, there was some evidence of an association between cognition and neurofilament‐light and neurogranin. Risk of bias in the field requires improvement (Created with Biorender.com).