Highlights
- •Accurate diagnosis of behavioural variant frontotemporal dementia is challenging.
- •bvFTD is commonly misdiagnosed, and distinguishing from non-progressor mimics is challenging.
- •The biomarker of neuronal injury, neurofilament light, improves diagnostic confidence in bvFTD.
Abstract
Background: Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non-neurodegenerative
‘non-progressor’ mimics of frontal lobe dysfunction, can be one of the most challenging
clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL),
could reduce misdiagnosis and delay.
Methods: Cerebrospinal fluid (CSF) NfL, amyloid beta 1–42 (AB42), total and phosphorylated
tau (T-tau, P-tau) levels were examined in patients with an initial diagnosis of bvFTD.
Based on follow-up information, patients were categorised as Progressors or Non-Progressors:
further subtyped into Non-Progressor Revised (non-neurological/neurodegenerative final
diagnosis), and Non-Progressor Static (static deficits, not fully explained by non-neurological/neurodegenerative
causes).
Results: Forty-three patients were included: 20 Progressors, 23 Non-Progressors (15 Non-Progressor
Revised, 8 Non-Progressor Static), and 20 controls. NfL concentrations were lower
in Non-Progressors (Non-Progressors Mean, M = 554 pg/mL, 95%CI:[461, 675], Non-Progressor
Revised M = 459 pg/mL, 95%CI:[385, 539], and Non-Progressor Static M = 730 pg/mL,
95%CI:[516, 940]), compared to Progressors (M = 2397 pg/mL, 95%CI:[1607, 3332]). NfL
distinguished Progressors from Non-Progressors with the highest accuracy (area under
the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive
value, 88% accuracy). Non-Progressor Static tended to have higher T-tau and P-tau
levels compared to Non-Progressor Revised Diagnoses.
Conclusion: This study demonstrated strong diagnostic utility of CSF NfL to distinguish bvFTD
from non-progressor variants, at baseline, with high accuracy, in a real-world clinical
setting. This has important clinical implications, to improve outcomes for patients
and clinicians facing this challenging clinical dilemma, healthcare services, and
clinical trials. Further research is required to investigate heterogeneity within
the non-progressor group and potential diagnostic algorithms, and prospective studies
are underway assessing plasma NfL.
Keywords
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Article Info
Publication History
Published online: September 30, 2022
Accepted:
September 25,
2022
Received in revised form:
September 5,
2022
Received:
June 19,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
