Cited by 5,221Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

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

Open access
Rascovsky, Katya, Hodges, John R., Knopman, David, Mendez, Mario F., Kramer, Joel H., Neuhaus, John, van Swieten, John C., Seelaar, Harro +38 more·2011·Brain

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/brain/awr179

Cites

179 of 179 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Frontotemporal dementia is caused by frontotemporal lobar degeneration (FTLD), which features abnormal aggregation of tau (FTLD-tau) or transactivating DNA-binding protein 43.

    “Frontotemporal dementia is caused by frontotemporal lobar degeneration (FTLD), which features abnormal aggregation of the microtubule associated protein consisting of tau (FTLD-tau) or the transactivating DNA-binding protein 43.16,18–20”

    From Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia (2020) · cites this paper as [19]

    The section headed “Development of the Proposed Classification of PPA and Its Variants” (page unavailable) identifies tau-positive and TDP-43-positive FTLD pathology, supporting the protein-pathology portion of the claim. It discusses primary progressive aphasia, however, and also identifies Alzheimer pathology as a possible cause; it does not establish that frontotemporal dementia as a whole is caused by FTLD or that these are its only pathological forms. (LLM, conf=0.79)

    Experimental — accuracy not yet measured
  • In bvFTD, language dysfunction is initially absent, unlike other frontotemporal dementia phenotypes (progressive nonfluent aphasia and semantic dementia).

    “In bvFTD, language dysfunction is initially absent, unlike other frontotemporal dementia phenotypes, namely progressive nonfluent aphasia and semantic dementia [17].”

    From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [17]

    The indexed section headed “Classification of primary progressive aphasia and its variants” describes language impairments in the nonfluent and semantic variants (page not provided). It does not establish that language dysfunction is initially absent in bvFTD, which is the central contrast in the citing sentence. (LLM, conf=0.78)

    Experimental — accuracy not yet measured
  • The machine learning model was trained on a mainly sporadic cohort and tested in a held-out population of genetic bvFTD to ensure generalizability.

    “To ensure the generalizability of the results, the machine learning model was trained on a mainly sporadic cohort and tested in a held-out population of genetic bvFTD, therefore relying on one of the gold standards for diagnosis (i.e., definite bvFTD). 7”

    From MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia (2021) · cites this paper as [7]

    The supplied passages are labeled as a paper on primary progressive aphasia, despite the cited DOI being identified as a bvFTD paper. Searches for machine-learning training, a mainly sporadic cohort, held-out genetic bvFTD cases, and definite bvFTD returned no passage addressing the claim; the available text discusses definite pathology for PPA instead. (LLM, conf=0.75)

    Experimental — accuracy not yet measured
  • The performance of the classifier is superior to the performance reported for standard diagnostic methods currently used in clinical practice.

    “The performance of our classifier is superior than the performance reported in several articles that have analyzed the standard diagnostic methods currently used in the clinical practice.”

    From MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia (2021) · cites this paper as [7]

    The indexed passages are labelled as a paper on primary progressive aphasia, despite the cited DOI being for Rascovsky et al. The Discussion passage addresses consistency of diagnostic criteria across centres, but none of the available passages reports the performance of standard clinical diagnostic methods for comparison with the citing authors’ classifier. Searches for revised behavioural-variant frontotemporal dementia criteria and diagnostic sensitivity returned only the aphasia passages; no page numbers were supplied. (LLM, conf=0.76)

    Experimental — accuracy not yet measured
  • Within a pathology-confirmed cohort, the sensitivity of the revised diagnostic criteria for bvFTD was 86% for possible diagnosis and 75% for probable bvFTD with neuroimaging support.

    “Within a pathology-confirmed cohort, the sensitivity reported for the revised diagnostic criteria for bvFTD was 86% for possible diagnosis and 75% for probable bvFTD (with neuroimaging support). 7”

    From MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia (2021) · cites this paper as [7]

    The indexed passages are labelled as sections of “Classification of primary progressive aphasia and its variants” and discuss PPA criteria, not sensitivity of bvFTD criteria. Searches for 86%, 75%, and possible and probable bvFTD found no passage reporting the claimed results. The available copy therefore cannot verify the figures or the pathology-confirmed cohort. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 46

  1. [1]1. Pick A. Uber die Beziehungen der senilen Hirnatrophie zur Aphasie. Prager Medizinische Wochenschrift 1892;17: 165-167.
  2. [2]2. Serieux P. Sur un cas de surdite verbale pure. Rev Med 1893;13:733-750.
  3. [3]3. Mesulam MM. Slowly progressive aphasia without gener- alized dementia. Ann Neurol 1982;11:592-598.
  4. [4]4. Mesulam MM, Weintraub S. Spectrum of primary pro- gressive aphasia. Baillieres Clin Neurol 1992;1:583-609.
  5. [5]5. Warrington EK. The selective impairment of semantic memory. Q J Exp Psychol 1975;27:635-657.
  6. [6]6. Snowden JS, Goulding PJ, Neary D. Semantic dementia: a form of circumscribed cerebral atrophy. Behav Neurol 1989;2:167-182.
  7. [7]7. Hodges JR, Patterson K, Oxbury S, Funnell E. Semantic dementia: progressive fluent aphasia with temporal lobe atrophy. Brain 1992;115:1783-1806.
  8. [8]8. Grossman M, Mickanin J, Onishi K, et al. Progressive non-fluent aphasia: language, cognitive and PET measures contrasted with probable Alzheimer's disease. J Cogn Neu- rosci 1996;8:135-154.
  9. [10]10. Grossman M, Ash S. Primary progressive aphasia: a review. Neurocase 2004;10:3-18.
  10. [11]11. Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary pro- gressive aphasia. Ann Neurol 2004;55:335-346.
  11. [12]12. Nestor PJ, Graham NL, Fryer TD, Williams GB, Patter- son K, Hodges JR. Progressive non-fluent aphasia is associ- ated with hypometabolism centered on the left anterior insula. Brain 2003;126:2406 -2418.
  12. [13]13. Josephs KA, Duffy JR, Strand EA, et al. Clinicopathologi- cal and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006;129:1385-1398.
  13. [14]14. Mummery CJ, Patterson K, Price CJ, Ashburner J, Frack- owiak RS, Hodges JR. A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atro- phy and semantic memory. Ann Neurol 2000;47:36 -45.
  14. [16]16. Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal de- mentia. Brain 2005;128:1996 -2005.
  15. [18]18. Forman MS, Farmer J, Johnson JK, et al. Frontotemporal dementia: clinicopathological correlations. Ann Neurol 2006;59:952-962.
  16. [19]19. Knibb JA, Xuereb JH, Patterson K, Hodges JR. Clinical and pathological characterization of progressive aphasia. Ann Neurol 2006;59:156 -165.
  17. [20]20. Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and frontotemporal pathology in subsets of primary pro- gressive aphasia. Ann Neurol 2008;63:709 -719.
  18. [21]21. Davies RR, Hodges JR, Kril JJ, Patterson K, Halliday GM, Xuereb JH. The pathological basis of semantic dementia. Brain 2005;128:1984 -1995.
  19. [22]22. Grossman M, Wood EM, Moore P, et al. TDP-43 patho- logic lesions and clinical phenotype in frontotemporal lo- bar degeneration with ubiquitin-positive inclusions. Arch Neurol 2007;64:1449 -1454.
  20. [23]23. Nestor PJ, Balan K, Cheow HK, et al. Nuclear imaging can predict pathologic diagnosis in progressive nonfluent aphasia. Neurology 2007;68:238 -239.
  21. [24]24. Rabinovici GD, Jagust WJ, Furst AJ, et al. Abeta amyloid and glucose metabolism in three variants of primary pro- gressive aphasia. Ann Neurol 2008;64:388 -401.
  22. [25]25. Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron 2009;62:42-52.
  23. [26]26. Snowden JS, Pickering-Brown SM, Mackenzie IR, et al. Progranulin gene mutations associated with frontotempo- ral dementia and progressive non-fluent aphasia. Brain 2006;129:3091-3102.
  24. [27]27. Mesulam M, Johnson N, Krefft TA, et al. Progranulin mutations in primary progressive aphasia: the PPA1 and PPA3 families. Arch Neurol 2007;64:43-47.
  25. [28]28. van Swieten J, Spillantini MG. Hereditary frontotemporal dementia caused by tau gene mutations. Brain Pathol 2007;17:63-73.
  26. [29]29. Krefft TA, Graff-Radford NR, Dickson DW, Baker M, Castellani RJ. Familial primary progressive aphasia. Alzhei- mer Dis Assoc Disord 2003;17:106 -112.
  27. [30]30. Snowden JS, Pickering-Brown SM, Du Plessis D, et al. Pro- gressive anomia revisited: focal degeneration associated with progranulin gene mutation. Neurocase 2007;13:366 -377.
  28. [32]32. Mesulam MM. Primary progressive aphasia. Ann Neurol 2001;49:425-432.
  29. [33]33. Mesulam MM. Primary progressive aphasia: a language- based dementia. N Engl J Med 2003;349:1535-1542.
  30. [34]34. Mesulam M, Weineke C, Rogalski E, Cobia D, Thomp- son C, Weintraub S. Quantitative template for subtyping primary progressive aphasia. Arch Neurol 2009;66:1545- 1551.
  31. [35]35. Libon DJ, Xie SX, Wang X, et al. Neuropsychological de- cline in frontotemporal lobar degeneration: a longitudinal analysis. Neuropsychology 2009;23:337-346.
  32. [36]36. Ogar JM, Dronkers NF, Brambati SM, Miller BL, Gorno- Tempini ML. Progressive nonfluent aphasia and its char- acteristic motor speech deficits. Alzheimer Dis Assoc Disord 2007;21:S23-S30.
  33. [37]37. Hodges JR, Patterson K. Nonfluent progressive aphasia and semantic dementia: a comparative neuropsychological study. J Int Neuropsychol Soc 1996;2:511-524.
  34. [38]38. Peelle JE, Troiani V, Gee J, et al. Sentence comprehension and voxel-based morphometry in progressive nonfluent aphasia, semantic dementia, and nonaphasic frontotempo- ral dementia. J Neurolinguistics 2008;21:418 -432.
  35. [39]39. Bozeat S, Lambon Ralph MA, Patterson K, Garrard P, Hodges JR. Non-verbal semantic impairment in semantic dementia. Neuropsychologia 2000;38:1207-1215.
  36. [41]41. Adlam AL, Patterson K, Rogers TT, et al. Semantic de- mentia and fluent primary progressive aphasia: two sides of the same coin? Brain 2006;129:3066 -3080.
  37. [42]42. Evans JJ, Heggs AJ, Antoun N, Hodges JR. Progressive prosopagnosia associated with selective right temporal lobe atrophy: a new syndrome? Brain 1995;118:1-13.
  38. [43]43. Gainotti G. Different patterns of famous people recogni- tion disorders in patients with right and left anterior tem- poral lesions: a systematic review. Neuropsychologia 2007; 45:1591-1607.
  39. [44]44. Yi HA, Moore P, Grossman M. Reversal of the concrete- ness effect for verbs in patients with semantic dementia. Neuropsychology 2007;21:9 -19.
  40. [45]45. Seeley WW, Bauer AM, Miller BL, et al. The natural his- tory of temporal variant frontotemporal dementia. Neurol- ogy 2005;64:1384 -1390.
  41. [46]46. Wilson SM, Brambati SM, Henry RG, et al. The neural basis of surface dyslexia in semantic dementia. Brain 2009; 132:71-86.
  42. [47]47. Meteyard L, Patterson K. The relation between content and structure in language production: an analysis of speech errors in semantic dementia. Brain Lang 2009;110:121- 134.
  43. [48]48. Galton CJ, Patterson K, Graham K, et al. Differing pat- terns of temporal atrophy in Alzheimer's disease and se- mantic dementia. Neurology 2001;57:216 -225.
  44. [49]49. Rosen HJ, Kramer JH, Gorno-Tempini ML, Schuff N, Weiner M, Miller BL. Patterns of cerebral atrophy in pri- mary progressive aphasia. Am J Geriatr Psychiatry 2002; 10:89 -97.
  45. [50]50. Gorno-Tempini ML, Brambati SM, Ginex V, et al. The logopenic/phonological variant of primary progressive aphasia. Neurology 2008;71:1227-1234.
  46. [51]51. Ash S, Moore P, Vesely L, et al. Non-fluent speech in frontotemporal lobar degeneration. Journal of Neurolin- guistics 2009;22:370 -383.

Cited by

Sorted by citations

Authors
Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., van Swieten, J. C., Seelaar, H., Dopper, E. G. P., Onyike, C. U., Hillis, A. E., Josephs, K. A., Boeve, B. F., Kertesz, A., Seeley, W. W., Rankin, K. P., Johnson, J. K., Gorno-Tempini, M.-L., Rosen, H., Prioleau-Latham, C. E., Lee, A., Kipps, C. M., Lillo, P., Piguet, O., Rohrer, J. D., Rossor, M. N., Warren, J. D., Fox, N. C., Galasko, D., Salmon, D. P., Black, S. E., Mesulam, M., Weintraub, S., Dickerson, B. C., Diehl-Schmid, J., Pasquier, F., Deramecourt, V., Lebert, F., Pijnenburg, Y., Chow, T. W., Manes, F., Grafman, J., Cappa, S. F., Freedman, M., Grossman, M., & Miller, B. L.
Affiliations
  • University of Pennsylvania (US)
  • UNSW Sydney (AU)
  • Mayo Clinic (US)
  • University of California, Los Angeles (US)
  • University of California, San Francisco (US)
  • Erasmus MC (NL)
  • Johns Hopkins University (US)
  • Western University (CA)
  • University Hospital Southampton NHS Foundation Trust (GB)
  • UCL Queen Square Institute of Neurology (GB)
  • University of California San Diego (US)
  • Sunnybrook Health Science Centre (CA)
  • Northwestern University (US)
  • Université de Lille (FR)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • University of Toronto (CA)
  • Favaloro University (AR)
  • Kessler Foundation (US)
  • Vita-Salute San Raffaele University (IT)
Venue
Brain
Published
2011-08-02
Volume
134
Issue
9
Pages
2456-2477
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
OpenAlex
W2128030851
Cited by
5,221
References
179
Citations by year
2026: 333 · 2025: 445 · 2024: 486 · 2023: 427 · 2022: 456 · 2021: 460 · 2020: 459 · 2019: 355 · 2018: 338 · 2017: 325 · 2016: 293 · 2015: 276 · 2014: 225 · 2013: 208 · 2012: 115
FWCI
122.40
Type
journal article
Language
en
Open access
Locations
  • Brain (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • Iris (University of Trento) (submittedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Alzheimer's Association
  • Bristol-Myers Squibb (AG17586)
  • Eli Lilly and Company (AG17586)
  • Pfizer (AG17586)
  • GlaxoSmithKline
  • Sanofi
  • Heart and Stroke Foundation of Canada
  • Baxter International
  • Wellcome Trust (091673)
  • Canadian Stroke Network
  • Myriad Genetics
  • Alzheimer Society
  • National Institute for Health and Care Research (NF-SI-0508-10123)
  • University of Cambridge
  • University of Oxford
  • Elan
  • Fonds Wetenschappelijk Onderzoek (P6/29)
  • Eisai
  • KU Leuven
  • Vlaamse regering
  • H. Lundbeck A/S
  • National Institutes of Health (DC008552, AG016574, AG023501, AG019724, NS53488, AG06786, AG 17586, AG13854, AG15116, AG16574, AG32953)
  • Canadian Institutes of Health Research (13129)
  • Natural Sciences and Engineering Research Council of Canada
  • National Institute on Aging (AG13854, P50‐AG16574, R01-AG15116, U01AG06786, RO1 AG15866, AG 16574, P01 AG-17586, U01AG006786, R01AG015116, P01AG017586, AG17586, R01AG034499, R01AG032306, AG019724, P01-AG32953, P01AG032953, P01AG019724, P50AG023501, P50AG016574)
  • National Institute on Deafness and Other Communication Disorders (AG13854, DC008552, R01DC005375)
  • National Institute of Neurological Disorders and Stroke (R01-NS44266, R01NS047691, R01NS044266)
  • National Center for Research Resources (UL1RR025741)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
behavioral variant frontotemporal dementia, diagnostic criteria, sensitivity, frontotemporal lobar degeneration, disinhibition, apathy, hyperorality, dysexecutive syndrome, functional disability, neuroimaging, diagnostic accuracy
MeSH terms
Aged, Behavior, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Sensitivity and Specificity, Reproducibility of Results, Guidelines as Topic, Frontotemporal Dementia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review