Cerebrospinal Fluid S100B and Alzheimer’s Disease Biomarkers in Hip Fracture Patients with Delirium

Abstract

Objectives: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. Methods: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method. A consensus-based diagnosis of prefracture dementia was made using all available information. CSF was drawn at the onset of spinal anesthesia. S100B and phosphorylated tau (P-tau) concentrations were measured using electrochemiluminescence immunoassay and enzyme-linked immunosorbent assays, respectively. Results: In the hip fracture population (n = 98) there was no significant difference in CSF S100B concentrations between patients with ongoing preoperative (i.e., prevalent) delirium (n = 36, median [interquartile range] 1.11 μg/L [0.91–1.29]) and patients who never developed delirium (n = 46, 1.08 μg/L [0.92–1.28], p = 0.92). In patients without preoperative delirium, those who developed delirium postoperatively (i.e., incident delirium) (n = 16, 1.38 μg/L [1.08–1.62]) had higher concentrations of S100B than the 46 who never did (p = 0.013). This difference was confined to patients with pathological concentrations of P-tau (≥60 ng/L, n = 38). We also found that P-tau and S100B were correlated in CSF in the elective surgery patients. Conclusions: CSF S100B was elevated in patients with incident delirium who also had pathological levels of the Alzheimer disease biomarker P-tau, suggesting vulnerability caused by a preexisting process of astrocytic activation and tau pathology.

Association of glial and neuronal degeneration markers with Alzheimer‘s disease cerebrospinal fluid profile and cognitive functions

“…Neither CSF S100B nor GFAP have been much studied in terms of correlation with CSF core AD markers. Hov et al [32] found similar results among elective surgery patients free from dementia and delirium, with S100B positively correlating with P-tau but not with Aβ 42 in CSF. Ishiki et al [33] did not nd an association between GFAP and the core AD markers within a sample of healthy subjects and dementia patients.…”

“…and GFAP with core AD markers in CSF. Hov et al [32] found an association between S100B and P-tau but not Aβ 42 among elective surgery patients free from dementia and delirium. Ishiki et al [33] did not nd an association between CSF GFAP and core markers within a dementia cohort.…”

CSF sTREM2 in delirium—relation to Alzheimer’s disease CSF biomarkers Aβ42, t-tau and p-tau

“…Thus, stratification of delirium-afflicted patients suggests that CSF sTREM2 increases transiently prior to delirium onset, but then declines. An early but transient glial response in delirium is supported by increased levels of other CSF biomarkers of immune responses in incident delirium, such as neopterin [ 40 ] and astroglia-derived S-100β [ 41 ]. Thus, CSF sTREM2 is a promising biomarker of microglial activation that is presumably more usable to detect transient responses, which is consistent with TREM2 having a rapid cell surface turnover (< 1 h) [ 42 ].…”

Neurofilament Light in Serum and Cerebrospinal Fluid of Hip Fracture Patients with Delirium

“…Dissimilar study populations as well as lack of tissue specificity for both S100B and neuron-specific enolase may partly explain the divergent reports. Only a minority of the published studies [13, 14, 16] have been performed in cerebrospinal fluid (CSF) and, since extracerebral sources of S100B and neuron-specific enolase may influence blood levels, serum changes may not solely reflect upon brain damage [23]. One preliminary study on serum phosphorylated neurofilament-heavy, a structural protein in neurons, found an association between phosphorylated neurofilament-heavy and delirium severity [24].…”