Diagnostic Accuracy of MRI and Additional [18F]FDG-PET for Behavioral Variant Frontotemporal Dementia in Patients with Late Onset Behavioral Changes

Vijverberg, Everard G.B.; Wattjes, Mike P.; Dols, Annemiek; Krudop, Welmoed; Möller, Christiane; Peters, Anne L.; Kerssens, Cora J.; Gossink, Flora; Prins, Niels D.; Stek, Max L.; Scheltens, Philip; Berckel, Bart N.M. van; Barkhof, Frederik; Pijnenburg, Yolande A.L.

doi:10.3233/jad-160285

Cited by 69 publications

(64 citation statements)

References 55 publications

(49 reference statements)

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“…Combining these CSF biomarkers showed a sensitivity of 91% with a specificity of 83% for probable/definite bvFTD. This results in a similar or even higher diagnostic accuracy for bvFTD than frontotemporal changes on neuroimaging [4,37,38]. Thus, we advocate the use of CSF, in particular, these three biomarkers, in the diagnostic process of patients with changes in the regulation of social, interpersonal, and personal conduct and cognitive impairment.…”

Section: Discussionmentioning

confidence: 93%

“…For example, the neuropsychiatric feature apathy is frequently present in both bvFTD and primary psychiatric disorders [3]. Although bvFTD and primary psychiatric disorders can often be discriminated through imaging techniques, these investigations have a relatively low sensitivity (magnetic resonance imaging [MRI]) or specificity ([ 18 F]‐fluorodeoxyglucose–positron emission tomography ([ 18 F]FDG‐PET)) [4]. Therefore, ancillary biomarkers that are able to distinguish between bvFTD and primary psychiatric disorders at a higher accuracy are needed.…”

Section: Introductionmentioning

confidence: 99%

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

Vijverberg

Dols

Krudop

et al. 2017

Alz & Dem Diag Ass & Dis Mo

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IntroductionTo 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).MethodWe 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.ResultsThe 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.DiscussionWe 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.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Vijverberg

Dols

Krudop

et al. 2017

Alz & Dem Diag Ass & Dis Mo

Self Cite

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“…Although FDG-PET often can be useful in helping to differentiate bvFTD from AD, frontotemporal hypometabolism can occur in frontal variants of AD as well as in primary psychiatric disorders, both of which can clinically resemble bvFTD. 107,108 There have been some recent exciting advances in the development of PET tracers designed to bind tau paired helical filaments (PHF), allowing one to see in vivo tau distribution. One such tracer that has been the most studied is 18 F-AV1451.…”

Section: Other Imaging Modalities In Bvftdmentioning

confidence: 99%

Neuroimaging in Dementia

et al. 2017

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Although the diagnosis of dementia still is primarily based on clinical criteria, neuroimaging is playing an increasingly important role. This is in large part due to advances in techniques that can assist with discriminating between different syndromes. Magnetic resonance imaging remains at the core of differential diagnosis, with specific patterns of cortical and subcortical changes having diagnostic significance. Recent developments in molecular PET imaging techniques have opened the door for not only antemortem but early, even preclinical, diagnosis of underlying pathology. This is vital, as treatment trials are underway for pharmacological agents with specific molecular targets, and numerous failed trials suggest that earlier treatment is needed. This article provides an overview of classic neuroimaging findings as well as new and cutting-edge research techniques that assist with clinical diagnosis of a range of dementia syndromes, with an emphasis on studies using pathologically proven cases.

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“…However, these criteria reported a sensitivity of 85% and specificity of 27% for possible bvFTD diagnosis in a clinically relevant cohort of patients with mixed behavioral changes, reaching 82% specificity when adding a compatible MRI scan (38). Within a cohort with late onset behavioral disorders, 70% sensitivity and 93% specificity have been reported for structural MRI alone for bvFTD assessed by an experienced neuroradiologist (8). The latter results have comparable positive and negative likelihood ratios to ours, even though our method does not rely on the expertise of the radiological observer.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the aforementioned heterogeneity in pathology and heritability, as well as the syndromic overlap with psychiatric disorders and other dementias, a confirmed bvFTD diagnosis is often difficult to achieve in the absence of a dominant genetic mutation. Indeed, although brain imaging with magnetic resonance imaging (MRI) is paramount to increase the level of diagnostic confidence, it lacks sensitivity, particularly in the initial stages of the disease, leading to erroneous or late diagnosis (7,8).…”

Section: Introductionmentioning

confidence: 99%

Data-driven algorithm for the diagnosis of behavioral variant frontotemporal dementia

Manera

Dadar

Swieten

et al. 2019

Preprint

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Abbreviations FTD: frontotemporal dementia GRN: progranulin MAPT: microtubule-associated protein tau C9orf72 : chromosome 9 open reading frame 72 bvFTD: behavioural variant of frontotemporal dementia MRI: magnetic resonance imaging CNCs: cognitively normal controls DBM: deformation-based morphometry FTLDNI: frontotemporal lobar degeneration neuroimaging initiative T1-w: T1 weighted GENFI: Genetic frontotemporal dementia initiative MMSE: Mini mental state examination MOCA: Montreal cognitive assessment FTLD-CDR: Frontotemporal lobar degeneration Clinical Dementia Rating score CGI: Clinical global impression FRS: Frontotemporal dementia rating scale FDR: False Discovery Rate PCA: Principal component analysis PCs: Principal components SF: Semantic fluency ROC: Receiver operating characteristic curves AUC: Area under the curve LR+: positive likelihood ratio LR-: negative likelihood ratio Abstract INTRODUCTION: Brain structural imaging is paramount for the diagnosis of behavioral variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis. METHODS:A total of 515 subjects from two different bvFTD databases (training and validation cohorts) were included to perform voxel-wise deformation-based morphometry analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from morphometric differences in isolation and together with bedside cognitive scores. RESULTS:Average ten-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In a separate validation cohort of genetically confirmed bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added cognitive scores. DISCUSSION:The random forest classifier developed can accurately predict bvFTD at the individual subject level.

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Diagnostic Accuracy of MRI and Additional [18F]FDG-PET for Behavioral Variant Frontotemporal Dementia in Patients with Late Onset Behavioral Changes

Cited by 69 publications

References 55 publications

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

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

Neuroimaging in Dementia

Data-driven algorithm for the diagnosis of behavioral variant frontotemporal dementia

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