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Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia
Open accessAbstract
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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In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measured
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“All patients (n = 96) were clinically evaluated by expert neurologists (M.G., D.J.I.) at the time of recording at the frontotemporal degeneration center (FTDC) in the neurology department of the Hospital of the University of Pennsylvania, and they were classified at a weekly consensus meeting at the FTDC using established clinical criteria.”
From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [27]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“the atrophy of specific brain regions shown by structural MRI is an important part of the diagnostic criteria for FTD and AD (McKhann et al., 2011; Rascovsky et al., 2011)”
From Deep Learning-Based Classification and Voxel-Based Visualization of Frontotemporal Dementia and Alzheimer's Disease (2021) · cites this paper as Rascovsky et al., 2011
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Based on these criteria, a degree of probability of underlying frontotemporal lobar degeneration can be attributed to cases presenting with at least three of five behavioural criteria and one cognitive criterion.”
From Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations (2022) · cites this paper as [3]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The clinical diagnosis of behavioural variant frontot emporal dementia is based on consensus diagnostic criteria that have been derived from an international cohort of 406 pathologically verified cases of frontotemporal dementia.3”
From Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations (2022) · cites this paper as [3]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Atrophy in the frontal or temporal lobes, which can be either symmetrical or very focal or asymmetrical, supports the clinical suspicion of frontotemporal dementia.3,4”
From Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations (2022) · cites this paper as [3]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“lack of support is more concerning for these carers especially when behavioural symptoms are severe (Gorno-Tempini et al. , 2011; Rascovsky et al. , 2011)”
From Which interventions work for dementia family carers?: an updated systematic review of randomized controlled trials of carer interventions. (2018) · cites this paper as Rascovsky et al., 2011
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Contrary to popular belief, executive dysfunction is not always the most prominent deficit in bvFTD and may not even be present on formal neuropsychological test results in the early stages (Pachana et al. , 1996; Kipps et al. , 2008; Rascovsky et al. , 2011).”
From Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders (2020) · cites this paper as Rascovsky et al. , 2011
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The presence of pathological atrophy in frontal or anterior temporal areas increases the bvFTD diagnostic certainty from 'possible' to 'probable' in current diagnostic criteria (Rascovsky et al. , 2011), which increases the specificity from 82% to 95% (Harris et al. , 2013).”
From Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders (2020) · cites this paper as Rascovsky et al. , 2011
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In addition, many of the DSM-5 specific dementia categories have separate criteria sets for 'Probable' and 'Possible' , which in most cases have been adapted from the neurological literature 88-91 .”
From An organization‐ and category‐level comparison of diagnostic requirements for mental disorders in ICD ‐11 and DSM ‐5 (2021) · cites this paper as [91]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“While semantic (category) fluency is usually impaired to a greater degree in fvAD, phonemic (letter) fluency is more affected in bvFTD [17].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [17]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The clinical diagnosis of bvFTD is currently based on the presence of behavioral changes antedating cognitive deficits with a sensitivity of 76–95% and specificity of 82–95% [16, 17].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [17]
Experimental — accuracy not yet measuredIn the citing paper
“Frontotemporal dementia (FTD) is a neurodegenerative disorder that predominantly affects the frontal and/or temporal lobes and presents with a spectrum of social, behavioral, language, psychiatric, and motor problems. 1 , 2 , 3”
From Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study (2024) · cites this paper as [2]
In the citing paper
“The development of the DSM-5 criteria for the various subtypes involved extensive discussions with experts from diverse fields to harmonize the DSM criteria with criteria developed by other expert groups, such as the NIA-AA, 20,27 the frontotemporal dementia expert group, 28,29 the consortium on DLB, 30 the VASCOG working group, 31 the Movement Disorder Study Task Force on Parkinson Disease 32 and”
From Classifying neurocognitive disorders: the DSM-5 approach (2014) · cites this paper as [29]
In the citing paper
“These criteria are consistent with those published by external expert groups, 28,29 but it must be pointed out that the identification of frontotemporal degeneration as the aetiology for mild neurocognitive disorder in the absence of genetic and/or neuroimaging evidence is not yet established.”
From Classifying neurocognitive disorders: the DSM-5 approach (2014) · cites this paper as [29]
In the citing paper
“Second, patients received diagnoses based on established clinical criteria only,37,38 without testing for ATN biomarkers in AD such as the deposition of amyloid-β and tau proteins established via Positron Emission Tomography, CSF, or plasma in AD.94, 95, 96, 97”
From Altered spatiotemporal brain dynamics of interoception in behavioural-variant frontotemporal dementia (2025) · cites this paper as [37]
In the citing paper
“The diagnosis was concluded in a multidisciplinary meeting using consensus criteria for probable FTD, PPD (DSM-V), and AD [25,31,32].”
In the citing paper
“Final diagnoses were based on internationally established criteria [12, 46, 49–52].”
In the citing paper
“Two reviewers (JF and DP) evaluated the overall methodological quality of the full text papers taking into account eligibility criteria of (I) high diagnostic accuracy [i.e., probable or definite bvFTD by international diagnostic criteria (Rascovsky et al., 2011)]; (II) sample size; (III) follow-up time; (IIII) use of appropriate outcome measures, when weighing research evidence.”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Rascovsky et al., 2011
In the citing paper
“In current international diagnostic criteria, the cognitive profile of bvFTD is characterized by executive deficits, with relative sparing of memory and visuospatial functioning (Rascovsky et al., 2011).”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Rascovsky et al., 2011
In the citing paper
“Since bvFTD is marked by typical frontal and (anterior) temporal atrophy, hypometabolism or hypoperfusion (Rascovsky et al., 2011), the use of neuroimaging offers an essential measure of disease progression.”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Rascovsky et al., 2011
In the citing paper
“A logopenic variant of PPA (lvPPA) has also been described, but is usually associated with AD pathology.”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [5]
In the citing paper
“In current clinical practice, the place of CSF analysis is to exclude AD pathology and verify neurodegeneration—it does not have utility for affirmative diagnosis of FTD. 5”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [5]
In the citing paper
“Clinically, bvFTD is characterised by profound changes to behaviour and personality, with early brain atrophy observed in the ventromedial prefrontal cortex and insula (Rascovsky et al., 2011), extending to the temporal lobes and subcortical regions with disease progression (Landin-Romero et al., 2017).”
From Thinking versus feeling: How interoception and cognition influence emotion recognition in behavioural-variant frontotemporal dementia, Alzheimer's disease, and Parkinson's disease (2023) · cites this paper as Rascovsky et al., 2011
In the citing paper
“Diagnosis was established by the multidisciplinary teams at each research institute based on current consensus diagnostic criteria (McKhann et al., 2011; Postuma et al., 2015; Rascovsky et al., 2011).”
From Thinking versus feeling: How interoception and cognition influence emotion recognition in behavioural-variant frontotemporal dementia, Alzheimer's disease, and Parkinson's disease (2023) · cites this paper as Rascovsky et al., 2011
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Self-citationIncidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries
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Hypersexual behavior in frontotemporal dementia: a comparison with early-onset Alzheimer’s disease
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Kynurenic Acid Levels are Increased in the CSF of Alzheimer’s Disease Patients
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“Among them, the atrophy of specific brain regions shown by structural MRI is an important part of the diagnostic criteria for FTD and AD (McKhann et al., 2011; Rascovsky et al., 2011), and magnetic resonance scanning has become a standard procedure in the clinical workflow.”
BackgroundApathy: A neurocircuitry model based on frontotemporal dementia
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Self-citationLongitudinal change in everyday function and behavioral symptoms in frontotemporal dementia
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Self-citationAllostatic interoceptive overload in frontotemporal dementia
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Self-citationMagnetic resonance elastography of frontotemporal dementia
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Self-citationApathy in Frontotemporal Degeneration: Neuroanatomical Evidence of Impaired Goal-directed Behavior
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Self-citationPlasma tau is increased in frontotemporal dementia
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Meta-analytic review of memory impairment in behavioral variant frontotemporal dementia
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Self-citationProgression in Behavioral Variant Frontotemporal Dementia: A Longitudinal Study
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Self-citationPoly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers
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Self-citationAllostatic Interoceptive Overload Across Psychiatric and Neurological Conditions
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Self-citationO’Connor (2017) · doi:10.1212/wnl.0000000000004215 · Cited by 60
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Self-citationAssessing the “social brain” in dementia: applying TASIT-S
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“Diagnosis for bvFTD and AD was determined by consensus between the behavioural neurologist, neuropsychologist and occupational therapist according to current consensus criteria (McKhann et al. 2011; Rascovsky et al. 2011).”
Self-citationAutomatic measurement of prosody in behavioral variant FTD
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Self-citationDopper, E. G. P., Chalos, V., Ghariq, E., den Heijer, T., Hafkemeijer, A., Jiskoot, L. C., de Koning, I., Seelaar, H., van Minkelen, R., van Osch, M. J. P., et al. (2016) · NeuroImage: Clinical · doi:10.1016/j.nicl.2016.08.001 · Cited by 57
Self-citationReorganisation of brain networks in frontotemporal dementia and progressive supranuclear palsy
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Energy expenditure in frontotemporal dementia: a behavioural and imaging study
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Self-citationBiomarkers for diseases with TDP-43 pathology
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Hafkemeijer, A., Möller, C., Dopper, E. G. P., Jiskoot, L. C., van den Berg-Huysmans, A. A., van Swieten, J. C., van der Flier, W. M., Vrenken, H., Pijnenburg, Y. A. L., Barkhof, F., et al. (2016) · Journal of Alzheimer’s Disease · doi:10.3233/jad-150695 · Cited by 57
Self-citationBachli, M. B., Sedeño, L., Ochab, J. K., Piguet, O., Kumfor, F., Reyes, P., Torralva, T., Roca, M., Cardona, J. F., Campo, C. G., et al. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2019.116456 · Cited by 57
Self-citationTemporal irreversibility of large-scale brain dynamics in Alzheimer's disease
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Metadata
- 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)
- ORCID
- Hodges, John R.
- Knopman, David
- Mendez, Mario F.
- Kramer, Joel H.
- Neuhaus, John
- Seelaar, Harro
- Dopper, Elise G. P.
- Onyike, Chiadi U.
- Hillis, Argye E.
- Josephs, Keith A.
- Boeve, Bradley F.
- Kertesz, Andrew
- Seeley, William W.
- Rankin, Katherine P.
- Johnson, Julene K.
- Kipps, Christopher M.
- Lillo, Patricia
- Piguet, Olivier
- Rohrer, Jonathan D.
- Rossor, Martin N.
- Warren, Jason D.
- Fox, Nick C.
- Galasko, Douglas
- Salmon, David P.
- Black, Sandra E.
- Mesulam, Marsel
- Pasquier, Florence
- Deramecourt, Vincent
- Lebert, Florence
- Pijnenburg, Yolande
- Chow, Tiffany W.
- Manes, Facundo
- Grafman, Jordan
- Cappa, Stefano F.
- Freedman, Morris
- Grossman, Murray
- Miller, Bruce L.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-08-02
- Volume
- 134
- Issue
- 9
- Pages
- 2456-2477
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3170532
- 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
- bronze
- doi.org
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical 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 ›
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