Cerebrospinal fluid biomarker examination as a tool to discriminate behavioral variant frontotemporal dementia from primary psychiatric disorders

INTRODUCTION To prospectively determine the diagnostic value of cerebrospinal fluid (CSF) levels total-tau (tau) to amyloid-β1-42 ratio (Aβ1-42) ratio (tau/Aβ1-42 ratio), phosphorylated-tau (p-tau) to tau ratio (p-tau/tau ratio), neurofilament light chain (NfL) and YKL40 in the late-onset frontal lobe syndrome, in particular for the differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) versus primary psychiatric disorders (PSY). METHOD We included patients with a multidisciplinary 2-year-follow-up diagnosis of probable/definite bvFTD (n = 22) or PSY (n = 25), who underwent a detailed neuropsychiatric clinical examination, neuropsychological test battery, and magnetic resonance imaging at baseline. In all cases, CSF was collected through lumbar puncture at baseline. We compared CSF biomarker levels between the two groups and measured the diagnostic accuracy for probable/definite bvFTD, using the follow-up diagnosis as the reference standard. RESULTS The best discriminators between probable/definite bvFTD and PSY were the levels of CSF NfL (area under the curve [AUC] 0.93, P < .001, 95% confidence interval [CI] 0.85-1.00), p-tau/tau ratio (AUC 0.87, P < .001, 95% CI 0.77-0.97), and YKL40 (AUC 0.82, P = .001, 95% CI 0.68-0.97). The combination of these three biomarkers had a sensitivity of 91% (95% CI 66%-100%) at a specificity of 83% (95% CI 65%-95%) with an AUC of 0.94 (P < .001, 95% CI 0.87-1.00) for bvFTD. CSF tau/Aβ1-42 ratio was less accurate in differentiating between bvFTD and PSY. DISCUSSION We found a good diagnostic accuracy for higher levels of CSF NfL and YKL40 and reduced p-tau/tau ratio in distinguishing bvFTD from PSY. We advocate the use of these CSF biomarkers as potential additional tools to neuroimaging in the diagnosis of bvFTD versus PSY.