Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disorders

Lize C. Jiskoot; Lucy L. Russell; Caroline V. Greaves; Esther van Schaik; Esther van den Berg; Jackie M. Poos; Liset de Boer; Laura Donker Kaat; Harro Seelaar; Yolande A.L. Pijnenburg; John C. van Swieten; Jonathan D. Rohrer

doi:10.1007/s00415-023-11596-3

Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disorders

Lize C. Jiskoot^*, Lucy L. Russell, Caroline V. Greaves, Esther van Schaik, Esther van den Berg, Jackie M. Poos, Liset de Boer, Laura Donker Kaat, Harro Seelaar, Yolande A.L. Pijnenburg, John C. van Swieten, Jonathan D. Rohrer

^*Corresponding author for this work

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Abstract

Most neuropsychiatric symptoms (NPS) common in frontotemporal dementia (FTD) are currently not part of the Neuropsychiatric Inventory (NPI). We piloted an FTD Module that included eight extra items to be used in conjunction with the NPI. Caregivers of patients with behavioural variant FTD (n = 49), primary progressive aphasia (PPA; n = 52), Alzheimer’s dementia (AD; n = 41), psychiatric disorders (n = 18), presymptomatic mutation carriers (n = 58) and controls (n = 58) completed the NPI and FTD Module. We investigated (concurrent and construct) validity, factor structure and internal consistency of the NPI and FTD Module. We performed group comparisons on item prevalence, mean item and total NPI and NPI with FTD Module scores, and multinomial logistic regression to determine its classification abilities. We extracted four components, together explaining 64.1% of the total variance, of which the largest indicated the underlying dimension ‘frontal-behavioural symptoms’. Whilst apathy (original NPI) occurred most frequently in AD, logopenic and non-fluent variant PPA, the most common NPS in behavioural variant FTD and semantic variant PPA were loss of sympathy/empathy and poor response to social/emotional cues (part of FTD Module). Patients with primary psychiatric disorders and behavioural variant FTD showed the most severe behavioural problems on both the NPI as well as the NPI with FTD Module. The NPI with FTD Module correctly classified more FTD patients than the NPI alone. By quantifying common NPS in FTD the NPI with FTD Module has large diagnostic potential. Future studies should investigate whether it can also prove a useful addition to the NPI in therapeutic trials.

Original language	English
Pages (from-to)	2674-2687
Number of pages	14
Journal	Journal of Neurology
Volume	270
Issue number	5
Early online date	22 Feb 2023
DOIs	https://doi.org/10.1007/s00415-023-11596-3
Publication status	Published - May 2023

Bibliographical note

Funding Information:
The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI Grant (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX Grant (2019-02248), the Dioraphte Foundation [Grant Numbers 09-02-00], the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organization for Scientific Research (NWO) (Grant HCMI 056-13-018), ZonMw Memorabel (Deltaplan Dementie; project numbers 733050103 and 733050813), and JPND PreFrontAls Consortium (project number 733051042). JMP is supported by a fellowship award from Alzheimer Nederland (WE.15-2019.02).

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© 2023, The Author(s).

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Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disordersFinal published version, 1.62 MBLicence: CC BY

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Jiskoot, L. C., Russell, L. L., Greaves, C. V., van Schaik, E., van den Berg, E., Poos, J. M., de Boer, L., Donker Kaat, L., Seelaar, H., Pijnenburg, Y. A. L., van Swieten, J. C., & Rohrer, J. D. (2023). Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disorders. Journal of Neurology, 270(5), 2674-2687. Advance online publication. https://doi.org/10.1007/s00415-023-11596-3

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title = "Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disorders",

abstract = "Most neuropsychiatric symptoms (NPS) common in frontotemporal dementia (FTD) are currently not part of the Neuropsychiatric Inventory (NPI). We piloted an FTD Module that included eight extra items to be used in conjunction with the NPI. Caregivers of patients with behavioural variant FTD (n = 49), primary progressive aphasia (PPA; n = 52), Alzheimer{\textquoteright}s dementia (AD; n = 41), psychiatric disorders (n = 18), presymptomatic mutation carriers (n = 58) and controls (n = 58) completed the NPI and FTD Module. We investigated (concurrent and construct) validity, factor structure and internal consistency of the NPI and FTD Module. We performed group comparisons on item prevalence, mean item and total NPI and NPI with FTD Module scores, and multinomial logistic regression to determine its classification abilities. We extracted four components, together explaining 64.1% of the total variance, of which the largest indicated the underlying dimension {\textquoteleft}frontal-behavioural symptoms{\textquoteright}. Whilst apathy (original NPI) occurred most frequently in AD, logopenic and non-fluent variant PPA, the most common NPS in behavioural variant FTD and semantic variant PPA were loss of sympathy/empathy and poor response to social/emotional cues (part of FTD Module). Patients with primary psychiatric disorders and behavioural variant FTD showed the most severe behavioural problems on both the NPI as well as the NPI with FTD Module. The NPI with FTD Module correctly classified more FTD patients than the NPI alone. By quantifying common NPS in FTD the NPI with FTD Module has large diagnostic potential. Future studies should investigate whether it can also prove a useful addition to the NPI in therapeutic trials.",

author = "Jiskoot, {Lize C.} and Russell, {Lucy L.} and Greaves, {Caroline V.} and {van Schaik}, Esther and {van den Berg}, Esther and Poos, {Jackie M.} and {de Boer}, Liset and {Donker Kaat}, Laura and Harro Seelaar and Pijnenburg, {Yolande A.L.} and {van Swieten}, {John C.} and Rohrer, {Jonathan D.}",

note = "Funding Information: The Dementia Research Centre is supported by Alzheimer{\textquoteright}s Research UK, Alzheimer{\textquoteright}s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer{\textquoteright}s Society and Alzheimer{\textquoteright}s Research UK. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI Grant (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX Grant (2019-02248), the Dioraphte Foundation [Grant Numbers 09-02-00], the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organization for Scientific Research (NWO) (Grant HCMI 056-13-018), ZonMw Memorabel (Deltaplan Dementie; project numbers 733050103 and 733050813), and JPND PreFrontAls Consortium (project number 733051042). JMP is supported by a fellowship award from Alzheimer Nederland (WE.15-2019.02). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

doi = "10.1007/s00415-023-11596-3",

language = "English",

volume = "270",

pages = "2674--2687",

journal = "Journal of Neurology",

issn = "0340-5354",

publisher = "D. Steinkopff-Verlag",

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}

Jiskoot, LC, Russell, LL, Greaves, CV, van Schaik, E, van den Berg, E , Poos, JM, de Boer, L, Donker Kaat, L , Seelaar, H, Pijnenburg, YAL, van Swieten, JC & Rohrer, JD 2023, 'Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disorders', Journal of Neurology, vol. 270, no. 5, pp. 2674-2687. https://doi.org/10.1007/s00415-023-11596-3

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T1 - Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disorders

AU - Jiskoot, Lize C.

AU - Russell, Lucy L.

AU - Greaves, Caroline V.

AU - van Schaik, Esther

AU - van den Berg, Esther

AU - Poos, Jackie M.

AU - de Boer, Liset

AU - Donker Kaat, Laura

AU - Seelaar, Harro

AU - Pijnenburg, Yolande A.L.

AU - van Swieten, John C.

AU - Rohrer, Jonathan D.

N1 - Funding Information: The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI Grant (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX Grant (2019-02248), the Dioraphte Foundation [Grant Numbers 09-02-00], the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organization for Scientific Research (NWO) (Grant HCMI 056-13-018), ZonMw Memorabel (Deltaplan Dementie; project numbers 733050103 and 733050813), and JPND PreFrontAls Consortium (project number 733051042). JMP is supported by a fellowship award from Alzheimer Nederland (WE.15-2019.02). Publisher Copyright: © 2023, The Author(s).

PY - 2023/5

Y1 - 2023/5

N2 - Most neuropsychiatric symptoms (NPS) common in frontotemporal dementia (FTD) are currently not part of the Neuropsychiatric Inventory (NPI). We piloted an FTD Module that included eight extra items to be used in conjunction with the NPI. Caregivers of patients with behavioural variant FTD (n = 49), primary progressive aphasia (PPA; n = 52), Alzheimer’s dementia (AD; n = 41), psychiatric disorders (n = 18), presymptomatic mutation carriers (n = 58) and controls (n = 58) completed the NPI and FTD Module. We investigated (concurrent and construct) validity, factor structure and internal consistency of the NPI and FTD Module. We performed group comparisons on item prevalence, mean item and total NPI and NPI with FTD Module scores, and multinomial logistic regression to determine its classification abilities. We extracted four components, together explaining 64.1% of the total variance, of which the largest indicated the underlying dimension ‘frontal-behavioural symptoms’. Whilst apathy (original NPI) occurred most frequently in AD, logopenic and non-fluent variant PPA, the most common NPS in behavioural variant FTD and semantic variant PPA were loss of sympathy/empathy and poor response to social/emotional cues (part of FTD Module). Patients with primary psychiatric disorders and behavioural variant FTD showed the most severe behavioural problems on both the NPI as well as the NPI with FTD Module. The NPI with FTD Module correctly classified more FTD patients than the NPI alone. By quantifying common NPS in FTD the NPI with FTD Module has large diagnostic potential. Future studies should investigate whether it can also prove a useful addition to the NPI in therapeutic trials.

AB - Most neuropsychiatric symptoms (NPS) common in frontotemporal dementia (FTD) are currently not part of the Neuropsychiatric Inventory (NPI). We piloted an FTD Module that included eight extra items to be used in conjunction with the NPI. Caregivers of patients with behavioural variant FTD (n = 49), primary progressive aphasia (PPA; n = 52), Alzheimer’s dementia (AD; n = 41), psychiatric disorders (n = 18), presymptomatic mutation carriers (n = 58) and controls (n = 58) completed the NPI and FTD Module. We investigated (concurrent and construct) validity, factor structure and internal consistency of the NPI and FTD Module. We performed group comparisons on item prevalence, mean item and total NPI and NPI with FTD Module scores, and multinomial logistic regression to determine its classification abilities. We extracted four components, together explaining 64.1% of the total variance, of which the largest indicated the underlying dimension ‘frontal-behavioural symptoms’. Whilst apathy (original NPI) occurred most frequently in AD, logopenic and non-fluent variant PPA, the most common NPS in behavioural variant FTD and semantic variant PPA were loss of sympathy/empathy and poor response to social/emotional cues (part of FTD Module). Patients with primary psychiatric disorders and behavioural variant FTD showed the most severe behavioural problems on both the NPI as well as the NPI with FTD Module. The NPI with FTD Module correctly classified more FTD patients than the NPI alone. By quantifying common NPS in FTD the NPI with FTD Module has large diagnostic potential. Future studies should investigate whether it can also prove a useful addition to the NPI in therapeutic trials.

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Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disorders

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