Detecting frontotemporal dementia syndromes using MRI biomarkers

Marie Bruun, Juha Koikkalainen, Hanneke F. M. Rhodius-Meester, Marta Baroni, Le Gjerum, Mark van Gils, Hilkka Soininen, Anne M. Remes, P. ivi Hartikainen, Gunhild Waldemar, Patrizia Mecocci, Frederik Barkhof, Yolande Pijnenburg, Wiesje M. van der Flier, Steen G. Hasselbalch, Jyrki Lötjönen, Kristian S. Frederiksen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another. Methods: In this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200). Results: The anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index. Conclusion: This study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.
Original languageEnglish
Article number101711
JournalNeuroImage: Clinical
Volume22
Early online date4 Feb 2019
DOIs
Publication statusPublished - 2019

Cite this

Bruun, Marie ; Koikkalainen, Juha ; Rhodius-Meester, Hanneke F. M. ; Baroni, Marta ; Gjerum, Le ; van Gils, Mark ; Soininen, Hilkka ; Remes, Anne M. ; Hartikainen, P. ivi ; Waldemar, Gunhild ; Mecocci, Patrizia ; Barkhof, Frederik ; Pijnenburg, Yolande ; van der Flier, Wiesje M. ; Hasselbalch, Steen G. ; Lötjönen, Jyrki ; Frederiksen, Kristian S. / Detecting frontotemporal dementia syndromes using MRI biomarkers. In: NeuroImage: Clinical. 2019 ; Vol. 22.
@article{1efcbf4bb1424208ba5114c4496bbf9d,
title = "Detecting frontotemporal dementia syndromes using MRI biomarkers",
abstract = "Background: Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another. Methods: In this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48{\%} females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95{\%}. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200). Results: The anterior vs. posterior index performed with an AUC of 83{\%} for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59{\%}, Specificity = 95{\%}, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85{\%}, Sensitivity = 79{\%}, Specificity = 92{\%}, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85{\%}, Sensitivity = 82{\%}, Specificity = 80{\%}, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index. Conclusion: This study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.",
author = "Marie Bruun and Juha Koikkalainen and Rhodius-Meester, {Hanneke F. M.} and Marta Baroni and Le Gjerum and {van Gils}, Mark and Hilkka Soininen and Remes, {Anne M.} and Hartikainen, {P. ivi} and Gunhild Waldemar and Patrizia Mecocci and Frederik Barkhof and Yolande Pijnenburg and {van der Flier}, {Wiesje M.} and Hasselbalch, {Steen G.} and Jyrki L{\"o}tj{\"o}nen and Frederiksen, {Kristian S.}",
note = "Copyright {\circledC} 2019. Published by Elsevier Inc.",
year = "2019",
doi = "10.1016/j.nicl.2019.101711",
language = "English",
volume = "22",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",

}

Bruun, M, Koikkalainen, J, Rhodius-Meester, HFM, Baroni, M, Gjerum, L, van Gils, M, Soininen, H, Remes, AM, Hartikainen, PI, Waldemar, G, Mecocci, P, Barkhof, F, Pijnenburg, Y, van der Flier, WM, Hasselbalch, SG, Lötjönen, J & Frederiksen, KS 2019, 'Detecting frontotemporal dementia syndromes using MRI biomarkers' NeuroImage: Clinical, vol. 22, 101711. https://doi.org/10.1016/j.nicl.2019.101711, https://doi.org/10.1016/j.nicl.2019.101711

Detecting frontotemporal dementia syndromes using MRI biomarkers. / Bruun, Marie; Koikkalainen, Juha; Rhodius-Meester, Hanneke F. M.; Baroni, Marta; Gjerum, Le; van Gils, Mark; Soininen, Hilkka; Remes, Anne M.; Hartikainen, P. ivi; Waldemar, Gunhild; Mecocci, Patrizia; Barkhof, Frederik; Pijnenburg, Yolande; van der Flier, Wiesje M.; Hasselbalch, Steen G.; Lötjönen, Jyrki; Frederiksen, Kristian S.

In: NeuroImage: Clinical, Vol. 22, 101711, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Detecting frontotemporal dementia syndromes using MRI biomarkers

AU - Bruun, Marie

AU - Koikkalainen, Juha

AU - Rhodius-Meester, Hanneke F. M.

AU - Baroni, Marta

AU - Gjerum, Le

AU - van Gils, Mark

AU - Soininen, Hilkka

AU - Remes, Anne M.

AU - Hartikainen, P. ivi

AU - Waldemar, Gunhild

AU - Mecocci, Patrizia

AU - Barkhof, Frederik

AU - Pijnenburg, Yolande

AU - van der Flier, Wiesje M.

AU - Hasselbalch, Steen G.

AU - Lötjönen, Jyrki

AU - Frederiksen, Kristian S.

N1 - Copyright © 2019. Published by Elsevier Inc.

PY - 2019

Y1 - 2019

N2 - Background: Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another. Methods: In this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200). Results: The anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index. Conclusion: This study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.

AB - Background: Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another. Methods: In this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200). Results: The anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index. Conclusion: This study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30743135

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DO - 10.1016/j.nicl.2019.101711

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JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

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