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Classification of primary progressive aphasia and its variants
Open accessAbstract
This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA--nonfluent/agrammatic, semantic, and logopenic--were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as "imaging-supported" if the expected pattern of atrophy is found and "with definite pathology" if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.
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“Patients with primary progressive aphasias presenting as agrammatic, semantic or logopenic variants most commonly have frontotemporal lobar degeneration, but hippocampal sparing AD can also present in this manner [7, 102].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [102]
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
“One of the non‐amnestic AD presentations, logopenic variant primary progressive aphasia (lvPPA), is characterized by slow speaking rate with frequent partial words or false starts and frequent, long pauses due to word‐finding difficulties.”
From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [9]
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
“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 [9]
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
“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 [4]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Although separate clinical criteria have been defined for each variant of primary progressive aphasia, 4 on a clinical basis these disorders can be challenging to differentiate.”
From Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations (2022) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Consensus criteria for the primary progressive aphasia variants have also been described.4”
From Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations (2022) · cites this paper as [4]
The 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 Gorno-Tempini et al., 2011
Experimental — accuracy not yet measuredIn the citing paper
“However, the diagnostic criteria for svPPA and earlier criteria for FTD and semantic dementia (SD) allude to RATL involvement.”
From Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study (2024) · cites this paper as [3]
In the citing paper
“A separate variant with predominant right anterior temporal lobe (RATL) atrophy has been recognized, and labeled «right temporal variant FTD», «right‐lateralized SD», «right temporal lobe atrophy», «right temporal variant PPA», «right sided svPPA», and most recently «semantic behavioral variant FTD», 3 , 4 , 5 , 6 , 7 , 8 , 9 without consensus on its accompanying clinical syndrome. 10”
From Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study (2024) · cites this paper as [3]
In the citing paper
“Semantic deficits for people and objects across various sensory modalities, loss of empathy, and compulsions were mentioned in the criteria for svPPA as characteristics of RATL predominant svPPA, 3”
From Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study (2024) · cites this paper as [3]
In the citing paper
“although the latter has most often been underlying Alzheimer's disease (AD) pathology. 3”
From Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study (2024) · cites this paper as [3]
In 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 [3]
In the citing paper
“Previous publications have shown the semantic deficits for landmarks, 3 , 4 sound/audio, 17 , 18 smell/odor, 19 taste/flavor, 20 bodily sensations/interoceptive/somatic signals, 15 , 21 pain, and temperature 22 , 23 in small samples.”
From Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study (2024) · cites this paper as [3]
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 [28]
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 [28]
In the citing paper
“Clinical diagnosis of the FTD variants was based on current criteria (Armstrong et al., 2013; Gorno-Tempini et al., 2011; Rascovsky & Grossman, 2013; Rascovsky et al., 2011).”
From Multiclass characterization of frontotemporal dementia variants via multimodal brain network computational inference (2023) · cites this paper as Gorno-Tempini 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 [6]
In the citing paper
“Semantic dementia is a progressive neurodegenerative condition characterized by the profound and amodal loss of semantic memory in the context of relatively preserved episodic memory.”
From Considering the role of semantic memory in episodic future thinking: evidence from semantic dementia (2012) · cites this paper as Gorno-Tempini et al., 2011
In the citing paper
“All dementia patients met relevant clinical diagnostic criteria (McKhann et al., 1984;Neary et al., 1998;Gorno-Tempini et al., 2011).”
From Considering the role of semantic memory in episodic future thinking: evidence from semantic dementia (2012) · cites this paper as Gorno-Tempini et al., 2011
In the citing paper
“Specific clinical phenotype commonly associated with Alzheimer’s disease pathology (common Alzheimer’s disease phenotypes) are: the amnestic syndrome of the hippocampal type91 (typical), the posterior cortical atrophy variant,92 and the logopenic variant primary progressive aphasia93,94 (appendix p 2).”
From Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group (2021) · cites this paper as [93]
In the citing paper
“In the field of neurodegeneration, speech and language assessments are useful for diagnosing aphasic syndromes and for characterizing other disorders.”
From Speech and language markers of neurodegeneration: a call for global equity (2023) · cites this paper as [1]
In the citing paper
“Per current diagnostic criteria, speech and language impairments are the most salient feature in all persons with primary progressive aphasia. 1”
From Speech and language markers of neurodegeneration: a call for global equity (2023) · cites this paper as [1]
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“Impaired object knowledge may be present, and difficulty reading or spelling words with irregular orthography (surface alexia or agraphia) may also occur (Gorno-Tempini et al., 2011).”
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Metadata
- Authors
- Gorno-Tempini, M. L., Hillis, A. E., Weintraub, S., Kertesz, A., Mendez, M., Cappa, S. F., Ogar, J. M., Rohrer, J. D., Black, S., Boeve, B. F., Manes, F., Dronkers, N. F., Vandenberghe, R., Rascovsky, K., Patterson, K., Miller, B. L., Knopman, D. S., Hodges, J. R., Mesulam, M. M., & Grossman, M.
- Affiliations
- From the Memory and Aging Centre (M.L.G.-T., J.M.O., K.R., B.L.M.), Department of Neurology, University of California at San Francisco, San Francisco; Center for Mind/Brain Sciences (M.L.G.-T.), University of Trento, Trento, Italy; Department of Neurology (A.E.H.), Johns Hopkins University, Baltimore, MD; Department of Neurology (S.W., M.M.M.), Northwestern University, Chicago, IL; Cognitive Neurology (A.K.), University of Western Ontario, London, Canada; Department of Neurology (M.M.), University...
- Northwestern University (US)
- ORCID
- Venue
- Neurology
- Published
- 2011-03-15
- Volume
- 76
- Issue
- 11
- Pages
- 1006-1014
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3059138
- OpenAlex
- W2138190873
- Cited by
- 5,141
- References
- 51
- Citations by year
- 2026: 340 · 2025: 424 · 2024: 439 · 2023: 395 · 2022: 449 · 2021: 455 · 2020: 431 · 2019: 391 · 2018: 331 · 2017: 293 · 2016: 263 · 2015: 249 · 2014: 212 · 2013: 222 · 2012: 160
- FWCI
- 143.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, other-oa)
- UCL Discovery (University College London) (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
- Canadian Stroke Network
- Myriad Genetics
- Alzheimer Society
- 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 (AG019724, NS53488, AG 17586, AG13854, AG16574, AG17586, AG15116, NS44266, NS53488)
- Forest Laboratories
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Australian Research Council
- National Institute on Aging (AG15116, R01AG015866, AG13854, RO1 AG15866, AG 16574, U01AG006786, R01AG015116, P01AG017586, AG17586, R01AG034499, AG019724, U24AG026395, P30AG013854, U19AG010483, P01AG019724, P50AG023501, P50AG016574)
- National Institute on Deafness and Other Communication Disorders (AG13854, R01DC008552, DC008552, R01DC005375)
- National Institute of Neurological Disorders and Stroke (NS53488, NS-44266, P50NS053488, R0I NS047691, R01NS047691, R01NS044266, R01NS050915)
- National Center for Research Resources (UL1RR025741)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neurobiology of Language and Bilingualism
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- primary progressive aphasia, nonfluent/agrammatic variant, semantic variant, logopenic variant, clinical criteria, brain atrophy patterns, clinicopathological correlation, biomarkers
- MeSH terms
- Atrophy, Brain, Dementia, Humans, Neuropsychological Tests, Aphasia, Primary Progressive
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