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

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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.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00415-023-11596-3.

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Most cited references 52

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Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.

Katya Rascovsky, John R. Hodges, David Knopman … (2011)

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

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Author and article information

Contributors

Lize C. Jiskoot:

ORCID: http://orcid.org/0000-0002-1120-1858

l.c.jiskoot@erasmusmc.nl

Journal

Journal ID (nlm-ta): J Neurol

Journal ID (iso-abbrev): J Neurol

Title: Journal of Neurology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0340-5354

ISSN (Electronic): 1432-1459

Publication date (Electronic): 22 February 2023

Publication date PMC-release: 22 February 2023

Publication date (Print): 2023

Volume: 270

Issue: 5

Pages: 2674-2687

Affiliations

[1 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Neurology and Alzheimer Center Erasmus MC, , Erasmus MC University Medical Center, ; Room NF-331, Dr. Molenwaterplein 40, 3015 CE Rotterdam, The Netherlands

[2 ]GRID grid.83440.3b, ISNI 0000000121901201, Dementia Research Centre, Department of Neurodegenerative Disease, , University College London Queen Square Institute of Neurology, ; London, UK

[3 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Clinical Genetics, , Erasmus Medical Center, ; Rotterdam, The Netherlands

[4 ]GRID grid.509540.d, ISNI 0000 0004 6880 3010, Department of Neurology, , Amsterdam University Medical Centre, ; Amsterdam, The Netherlands

[5 ]GRID grid.83440.3b, ISNI 0000000121901201, Dementia Research Centre (DRC), National Hospital for Neurology and Neurosurgery, , University College London (UCL), ; 8-11 Queen Square, Box 16, London, WC1N 3BG UK

Author information

Lize C. Jiskoot http://orcid.org/0000-0002-1120-1858

Article

Publisher ID: 11596

DOI: 10.1007/s00415-023-11596-3

PMC ID: 10129920

PubMed ID: 36811680

SO-VID: f4486803-b610-4e4b-b9a9-1c4e4a16e109

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 19 December 2022

Date revision received : 26 January 2023

Date accepted : 28 January 2023

Funding

Funded by: Alzheimer’s Research UK

Funded by: Alzheimer’s Society

Funded by: Brain Research UK

Funded by: FundRef http://dx.doi.org/10.13039/501100001320, Wolfson Foundation;

Funded by: NIHR UCL/H Biomedical Research Centre

Funded by: the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility

Funded by: FundRef http://dx.doi.org/10.13039/501100017510, UK Dementia Research Institute;

Funded by: Miriam Marks Brain Research UK Senior Fellowship

Funded by: MRC Clinician Scientist Fellowship

Award ID: MR/M008525/1

Award Recipient : Jonathan D. Rohrer

Funded by: NIHR Rare Disease Translational Research Collaboration

Award ID: BRC149/NS/MH

Award Recipient : Jonathan D. Rohrer

Funded by: MRC UK GENFI grant

Award ID: MR/M023664/1

Funded by: the Bluefield Project

Funded by: JPND GENFI-PROX grant

Award ID: 2019-02248

Funded by: the Dioraphte Foundation

Award ID: 09-02-00

Funded by: the Association for Frontotemporal Dementias Research

Award ID: 2009

Funded by: NWO

Award ID: HCMI 056-13-018

Funded by: ZonMw Memorabel

Award ID: 733050103

Award ID: 733050813

Funded by: JPND PreFrontAls Consortium

Award ID: 733051042

Funded by: FundRef http://dx.doi.org/10.13039/501100010969, Alzheimer Nederland;

Award ID: WE.15-2019.02

Award Recipient : Jackie M. Poos

Custom metadata

ScienceOpen disciplines: Neurology

Keywords: neuropsychiatric symptoms,neuropsychiatric inventory,dementia,ftd,classification

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ScienceOpen disciplines: Neurology

Keywords: neuropsychiatric symptoms, neuropsychiatric inventory, dementia, ftd, classification

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

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Karger: Neurology and Neuroscience

Most cited references 52

"Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.

The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.

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