Development of a diagnostic checklist to identify functional cognitive disorder versus other neurocognitive disorders

Verónica Cabreira¹, Jane Alty², Sonja Antic³, Rui Araujo^{4

5}, Selma Aybek⁶, Harriet A Ball⁷, Gaston Baslet^{8

9}, Rohan Bhome^{10

11}, Jan Coebergh¹², Bruno Dubois^{13

14}, Mark Edwards¹⁵, Sasa R Filipovic¹⁶, Kristian Steen Frederiksen^{17

18}, Thomas Harbo³, Bradleigh Hayhow^{19

20}, Robert Howard²¹, Jonathan Huntley^{21

22}, Jeremy Darryl Isaacs²³, Curt LaFrance^{24

25}, Andrew Larner²⁶, Francesco Di Lorenzo²⁷, James Main²⁸, Elizabeth Mallam²⁹, Camillo Marra³⁰, João Massano^{4

5}, Emer R McGrath³¹, Isabel Portela Moreira³², Flavio Nobili³³, Suvankar Pal^{34

35}, Catherine M Pennington^{1

35}, Miguel Tábuas-Pereira^{36

37}, David Perez³⁸, Stoyan Popkirov³⁹, Dane Rayment⁴⁰, Martin Rossor⁴¹, Mirella Russo⁴², Isabel Santana^{36

43}, Jonathan Schott⁴⁴, Emmi P Scott⁴⁵, Ricardo Taipa⁴⁶, Tiago Teodoro⁴⁷, Michele Tinazzi⁴⁸, Svetlana Tomic⁴⁹, Sofia Toniolo⁵⁰, Caroline Winther Tørring³, Tim Wilkinson¹, Martin Zeidler⁵¹, Lisbeth Frostholm^{52

53}, Laura McWhirter¹, Jon Stone¹, Alan Carson¹

Affiliations

¹ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
² Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia.
³ Neurology, Aarhus Universitetshospital, Aarhus, Denmark.
⁴ Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal.
⁵ Clinical Neurosciences and Mental Health, University of Porto Faculty of Medicine, Porto, Portugal.
⁶ Neurology, University of Fribourg Faculty of Science and Medicine, Fribourg, Switzerland.
⁷ University of Bristol Faculty of Health Sciences, Bristol Medical School, Bristol, UK.
⁸ Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁹ Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Dementia Research Centre, University College London, London, UK.
¹¹ Centre for Medical Image Computing, University College London, London, UK.
¹² St George's University of London, London, London, UK.
¹³ Department of Neurology, Institut de la mémoire et de la maladie d'Alzheimer, Centre de Référence 'Démences Rares', Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.
¹⁴ ICM-INSERM 1127, FrontLab, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
¹⁵ Department of Basic and Clinical Neuroscience, King's College London Institute of Psychiatry Psychology and Neuroscience, London, UK.
¹⁶ Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
¹⁷ Clinical Trial Unit, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁸ Department of Clinical Medicine, University of Copenhagen, Kobenhavn, Denmark.
¹⁹ Neurology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
²⁰ School of Medicine, The University of Notre Dame Australia, Perth, Western Australia, Australia.
²¹ Division of Psychiatry, University College London, London, UK.
²² Camden and Islington NHS Foundation Trust, London, UK.
²³ Department of Neurology, St George's Hospital, London, UK.
²⁴ Alpert Medical School Area Health Education Centre, Providence, Rhode Island, USA.
²⁵ Neuropsychiatry and Behavioral Neurology, Rhode Island Hospital, Providence, Rhode Island, USA.
²⁶ Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
²⁷ Department of Clinical and Behavioural Neurology, Fondazione Santa Lucia Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy.
²⁸ Bristol Dementia Wellbeing Service, Devon Partnership NHS Trust, Bristol, UK.
²⁹ North Bristol NHS Trust, Westbury on Trym, UK.
³⁰ Universita Cattolica del Sacro Cuore Sede di Roma, Roma, Italy.
³¹ University of Galway School of Medicine, Galway, Ireland.
³² Neurology Department, Private Hospital of Gaia of the Trofa Saúde Group, Vila Nova de Gaia, Portugal.
³³ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
³⁴ Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK.
³⁵ Neurology, NHS Forth Valley, Stirling, UK.
³⁶ Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
³⁷ University of Coimbra Faculty of Medicine, Coimbra, Portugal.
³⁸ Neurology and Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁹ Department of Neurology, University Hospital Essen, Essen, Germany.
⁴⁰ Rosa Burden Centre for Neuropsychiatry, Southmead Hospital, Bristol, UK.
⁴¹ Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
⁴² Department of Sciences, Department of Neuroscience, Imaging and Clinical Sciences, Gabriele d'Annunzio University of Chieti and Pescara, Chieti, Italy.
⁴³ Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.
⁴⁴ Dementia Research Centre, Institute of Neurology, London, UK.
⁴⁵ Medical University of South Carolina, Charleston, South Carolina, USA.
⁴⁶ Neuropathology Unit, Centro Hospitalar Universitário de Santo António, Porto, Portugal.
⁴⁷ Neurology, St George's University of London, London, UK.
⁴⁸ Department of Neurosciences, Biomedicine and Movement, University of Verona, Verona, Italy.
⁴⁹ Neurology, University Hospital Center, Osijek, Croatia.
⁵⁰ Cognitive Disorder Clinic, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
⁵¹ Neurology, NHS Fife, Kirkcaldy, UK.
⁵² Department of Clinical Medicine, Aarhus Universitetshospital, Aarhus, Denmark.
⁵³ Department of Functional Disorders and Psychosomatics, Aarhus Universitetshospital, Aarhus, Denmark.

PMID: 40034653
PMCID: PMC11873336
DOI: 10.1136/bmjno-2024-000918

Development of a diagnostic checklist to identify functional cognitive disorder versus other neurocognitive disorders

Verónica Cabreira et al. BMJ Neurol Open. 2025.

. 2025 Feb 27;7(1):e000918.

doi: 10.1136/bmjno-2024-000918. eCollection 2025.

Authors

Affiliations

¹ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
² Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia.
³ Neurology, Aarhus Universitetshospital, Aarhus, Denmark.
⁴ Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal.
⁵ Clinical Neurosciences and Mental Health, University of Porto Faculty of Medicine, Porto, Portugal.
⁶ Neurology, University of Fribourg Faculty of Science and Medicine, Fribourg, Switzerland.
⁷ University of Bristol Faculty of Health Sciences, Bristol Medical School, Bristol, UK.
⁸ Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁹ Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Dementia Research Centre, University College London, London, UK.
¹¹ Centre for Medical Image Computing, University College London, London, UK.
¹² St George's University of London, London, London, UK.
¹³ Department of Neurology, Institut de la mémoire et de la maladie d'Alzheimer, Centre de Référence 'Démences Rares', Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.
¹⁴ ICM-INSERM 1127, FrontLab, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
¹⁵ Department of Basic and Clinical Neuroscience, King's College London Institute of Psychiatry Psychology and Neuroscience, London, UK.
¹⁶ Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
¹⁷ Clinical Trial Unit, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁸ Department of Clinical Medicine, University of Copenhagen, Kobenhavn, Denmark.
¹⁹ Neurology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
²⁰ School of Medicine, The University of Notre Dame Australia, Perth, Western Australia, Australia.
²¹ Division of Psychiatry, University College London, London, UK.
²² Camden and Islington NHS Foundation Trust, London, UK.
²³ Department of Neurology, St George's Hospital, London, UK.
²⁴ Alpert Medical School Area Health Education Centre, Providence, Rhode Island, USA.
²⁵ Neuropsychiatry and Behavioral Neurology, Rhode Island Hospital, Providence, Rhode Island, USA.
²⁶ Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
²⁷ Department of Clinical and Behavioural Neurology, Fondazione Santa Lucia Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy.
²⁸ Bristol Dementia Wellbeing Service, Devon Partnership NHS Trust, Bristol, UK.
²⁹ North Bristol NHS Trust, Westbury on Trym, UK.
³⁰ Universita Cattolica del Sacro Cuore Sede di Roma, Roma, Italy.
³¹ University of Galway School of Medicine, Galway, Ireland.
³² Neurology Department, Private Hospital of Gaia of the Trofa Saúde Group, Vila Nova de Gaia, Portugal.
³³ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
³⁴ Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK.
³⁵ Neurology, NHS Forth Valley, Stirling, UK.
³⁶ Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
³⁷ University of Coimbra Faculty of Medicine, Coimbra, Portugal.
³⁸ Neurology and Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁹ Department of Neurology, University Hospital Essen, Essen, Germany.
⁴⁰ Rosa Burden Centre for Neuropsychiatry, Southmead Hospital, Bristol, UK.
⁴¹ Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
⁴² Department of Sciences, Department of Neuroscience, Imaging and Clinical Sciences, Gabriele d'Annunzio University of Chieti and Pescara, Chieti, Italy.
⁴³ Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.
⁴⁴ Dementia Research Centre, Institute of Neurology, London, UK.
⁴⁵ Medical University of South Carolina, Charleston, South Carolina, USA.
⁴⁶ Neuropathology Unit, Centro Hospitalar Universitário de Santo António, Porto, Portugal.
⁴⁷ Neurology, St George's University of London, London, UK.
⁴⁸ Department of Neurosciences, Biomedicine and Movement, University of Verona, Verona, Italy.
⁴⁹ Neurology, University Hospital Center, Osijek, Croatia.
⁵⁰ Cognitive Disorder Clinic, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
⁵¹ Neurology, NHS Fife, Kirkcaldy, UK.
⁵² Department of Clinical Medicine, Aarhus Universitetshospital, Aarhus, Denmark.
⁵³ Department of Functional Disorders and Psychosomatics, Aarhus Universitetshospital, Aarhus, Denmark.

PMID: 40034653
PMCID: PMC11873336
DOI: 10.1136/bmjno-2024-000918

Abstract

Background: Functional cognitive disorder (FCD) poses a diagnostic challenge due to its resemblance to other neurocognitive disorders and limited biomarker accuracy. We aimed to develop a new diagnostic checklist to identify FCD versus other neurocognitive disorders.

Methods: The clinical checklist was developed through mixed methods: (1) a literature review, (2) a three-round Delphi study with 45 clinicians from 12 countries and (3) a pilot discriminative accuracy study in consecutive patients attending seven memory services across the UK. Items gathering consensus were incorporated into a pilot checklist. Item redundancy was evaluated with phi coefficients. A briefer checklist was produced by removing items with >10% missing data. Internal validity was tested using Cronbach's alpha. Optimal cut-off scores were determined using receiver operating characteristic curve analysis.

Results: A full 11-item checklist and a 7-item briefer checklist were produced. Overall, 239 patients (143 FCD, 96 non-FCD diagnoses) were included. The checklist scores were significantly different across subgroups (FCD and other neurocognitive disorders) (F(2, 236)=313.3, p<0.001). The area under the curve was excellent for both the full checklist (0.97, 95% CI 0.95 to 0.99) and its brief version (0.96, 95% CI 0.93 to 0.98). Optimal cut-off scores corresponded to a specificity of 97% and positive predictive value of 91% for identifying FCD. Both versions showed good internal validity (>0.80).

Conclusions: This pilot study shows that a brief clinical checklist may serve as a quick complementary tool to differentiate patients with neurodegeneration from those with FCD. Prospective blind large-scale validation in diverse populations is warranted.Cite Now.

Keywords: ALZHEIMER'S DISEASE; COGNITION; DEMENTIA.

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Conflict of interest statement

LM receives funding from the Scottish Government Chief Scientist Office. LM provides independent medical testimony in court cases regarding patients with functional disorders, is secretary of the British Neuropsychiatry Association, and receives research funding from the Scottish Government Chief Scientist Office. JSch reports personal fees from UptoDate, outside the submitted work, runs a self-help website for patients with functional neurological symptoms (www. neurosymptoms.org) which is free and has no advertising, provides independent medical testimony in personal injury and negligence cases regarding patients with functional disorders and is secretary of the International Functional Neurological Disorder Society. He is a Chief Scientists Office NHS Research Scotland Career Researcher. AC is a director of a limited personal services company that provides independent medical testimony in court cases on a range of neuropsychiatric topics on a 50% pursuer 50% defender basis, a paid associate editor of the Journal of Neurology Neurosurgery and Psychiatry, and unpaid president elect of the International Functional Neurological Disorder Society. DP has received honoraria for continuing medical education lectures in FND; royalties from Springer for a functional movement disorder textbook and honoraria from Elsevier for a functional neurological disorder textbook; is on the editorial boards of Brain and Behavior (paid), Epilepsy.

Figures

Figure 1. Schematic representation of checklist development. In light grey, published studies from our group that informed the checklist development stage. In orange, studies covered in this article. FCD, functional cognitive disorder.

Figure 2. (A, B) Bar plots with distribution of scores across FCD and non-FCD groups, for the full (A) and brief (B) versions of the checklist; (C) distribution of the full checklist scores across diagnostic groups (n≥5 only). AD, Alzheimer’s disease; bvFTD, behavioural variant of frontotemporal dementia; FCD, functional cognitive disorder; MCI, mild cognitive impairment; PPA, primary progressive aphasia.

Figure 3. ROC curves for FCD versus other neurocognitive diagnoses (n=239). Full checklist (11 items) on the left, and brief version (7 items) on the right, with FCD as positive state. Coordinates of the ROC curve used to determine cut-off values under the respective curve. A cut-off point maximising specificity and +PV, while keeping a reasonable sensitivity was chosen (grey row). AUC, area under the curve; FCD, functional cognitive disorder; +PV, positive predictive value; −PV, negative predictive value; ROC, receiver operating characteristic.

See this image and copyright information in PMC

References

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Development of a diagnostic checklist to identify functional cognitive disorder versus other neurocognitive disorders

Affiliations

Development of a diagnostic checklist to identify functional cognitive disorder versus other neurocognitive disorders

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Miscellaneous