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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)99-106
Number of pages8
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume7
DOIs
Publication statusPublished - 1 Apr 2017

Cite this

@article{8accdff5c5714d7da30911beb52dcc0a,
title = "Cerebrospinal fluid biomarker examination as a tool to discriminate behavioral variant frontotemporal dementia from primary psychiatric disorders",
abstract = "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.",
keywords = "Biomarker, Cerebrospinal fluid, Frontotemporal dementia, Neurofilament, p/t ratio, Psychiatric disorders, YKL40",
author = "Vijverberg, {Everard G.B.} and Annemiek Dols and Krudop, {Welmoed A.} and {Del Campo Milan}, Marta and Kerssens, {Cora J.} and Flora Gossink and Prins, {Niels D.} and Stek, {Max L.} and Philip Scheltens and Teunissen, {Charlotte E.} and Pijnenburg, {Yolande A.L.}",
year = "2017",
month = "4",
day = "1",
doi = "10.1016/j.dadm.2017.01.009",
language = "English",
volume = "7",
pages = "99--106",
journal = "Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring",
issn = "2352-8729",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Cerebrospinal fluid biomarker examination as a tool to discriminate behavioral variant frontotemporal dementia from primary psychiatric disorders

AU - Vijverberg, Everard G.B.

AU - Dols, Annemiek

AU - Krudop, Welmoed A.

AU - Del Campo Milan, Marta

AU - Kerssens, Cora J.

AU - Gossink, Flora

AU - Prins, Niels D.

AU - Stek, Max L.

AU - Scheltens, Philip

AU - Teunissen, Charlotte E.

AU - Pijnenburg, Yolande A.L.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - Biomarker

KW - Cerebrospinal fluid

KW - Frontotemporal dementia

KW - Neurofilament

KW - p/t ratio

KW - Psychiatric disorders

KW - YKL40

UR - http://www.scopus.com/inward/record.url?scp=85015215973&partnerID=8YFLogxK

U2 - 10.1016/j.dadm.2017.01.009

DO - 10.1016/j.dadm.2017.01.009

M3 - Article

VL - 7

SP - 99

EP - 106

JO - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

JF - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

SN - 2352-8729

ER -