Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults

It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-ꞵ (Aꞵ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in two samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein [FABP3], total-tau, neurogranin, and neurofilament light [NFL] (n=189, scans=721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by Aꞵ42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers

Cerebrospinal fluid levels of neopterin are elevated in delirium after hip fracture

Background: The inflammatory cell product neopterin is elevated in serum before and during delirium. This suggests a role for disordered cell-mediated immunity or oxidative stress. Cerebrospinal fluid (CSF) neopterin levels reflect brain neopterin levels more closely than serum levels. Here we hypothesized that CSF neopterin levels would be higher in delirium. Methods: In this prospective cohort study, 139 elderly patients with acute hip fracture were recruited in Oslo and Edinburgh. Delirium was diagnosed with the confusion assessment method performed daily pre-operatively and on the first 5 days post-operatively. Paired CSF and blood samples were collected at the onset of spinal anaesthesia. Neopterin levels were measured using high-performance liquid chromatography. Results: Sixty-four (46 %) of 139 hip fracture patients developed delirium perioperatively. CSF neopterin levels were higher in delirium compared to controls (median 29.6 vs 24.7 nmol/mL, p = 0.003), with highest levels in patients who developed delirium post-operatively. Serum neopterin levels were also higher in delirium (median 37.0 vs 27. 1 nmol/mL, p = 0.003). CSF neopterin remained significantly associated with delirium after controlling for relevant risk factors. Higher neopterin levels were associated with poorer outcomes (death or new institutionalization) 1 year after surgery (p = 0.02 for CSF and p = 0.03 for serum). Conclusions: This study is the first to examine neopterin in CSF from patients with delirium. Our findings suggest potential roles for activation of cell-mediated immune responses or oxidative stress in the delirium process. High levels of serum or CSF neopterin in hip fracture patients may also be useful in predicting poor outcomes