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.
“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]
In the development-of-classification section (page not provided), the paper links nonfluent/agrammatic and semantic PPA most often to FTLD pathology. It instead says AD might be the most common underlying pathology for logopenic PPA. It also says AD pathology can occur with each clinical presentation, but does not specify hippocampal-sparing AD. (LLM, conf=0.87)
Experimental — accuracy not yet measuredLogopenic 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.
“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]
In the section describing logopenic PPA (page not available), the paper says spontaneous speech is slow and has frequent pauses caused by word-finding problems. It does not describe frequent partial words or false starts, or specify that the pauses are long. It also says AD might be the most common underlying pathology, rather than defining lvPPA as an AD presentation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPatients were clinically evaluated by expert neurologists at the time of recording and classified at a weekly consensus meeting using established clinical criteria.
“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]
The 'Working Research Criteria' section sets out clinical criteria for classifying primary progressive aphasia, supporting the reference to established criteria. It does not describe the citing study’s patients, their evaluation at the time of recording, or a weekly consensus meeting at the FTDC. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAtrophy in the frontal or temporal lobes supports the clinical suspicion of frontotemporal dementia.
“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]
The development and diagnostic-features sections (page not provided) use frontal and temporal atrophy patterns to support diagnoses of specific primary progressive aphasia variants. They do not establish that frontal or temporal atrophy generally supports suspicion of frontotemporal dementia, or address the sentence’s symmetrical, focal, and asymmetrical patterns. (LLM, conf=0.83)
Experimental — accuracy not yet measuredAlthough separate clinical criteria have been defined for each variant of primary progressive aphasia, on a clinical basis these disorders can be challenging to differentiate.
“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]
Consensus criteria for the primary progressive aphasia variants have been described.
“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]
Lack of support is more concerning for carers of people with frontotemporal dementia especially when behavioural symptoms are severe.
“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
The section on PPA classification says behavioral disturbances can occur early, but it does not discuss carers or whether lack of support becomes more concerning as symptoms become severe. Searches for carer support, caregiver burden, and behavioral-symptom severity found no passage addressing that relationship. (LLM, conf=0.76)
Experimental — accuracy not yet measuredDiagnostic criteria for svPPA and earlier criteria for FTD and semantic dementia allude to RATL involvement.
“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]
A separate variant with predominant RATL atrophy has been recognized, labeled with various terms, without consensus on its accompanying clinical syndrome.
“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]
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.
“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]
The logopenic variant has most often been underlying Alzheimer's disease pathology.
“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]
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.
“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]
Previous publications have shown the semantic deficits for landmarks, sound/audio, smell/odor, taste/flavor, bodily sensations/interoceptive/somatic signals, pain, and temperature in small samples.
“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]
These frontotemporal criteria are consistent with external expert groups, but identification of frontotemporal degeneration as the aetiology for mild neurocognitive disorder without genetic or neuroimaging evidence is not yet established.
“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]
The development of DSM-5 criteria for various subtypes involved extensive discussions with experts from diverse fields to harmonize with other expert groups.
“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]
Clinical diagnosis of the FTD variants was based on current criteria.
“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
The logopenic variant of PPA is usually associated with AD pathology.
“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]
Semantic dementia is a progressive neurodegenerative condition.
“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
All dementia patients met relevant clinical diagnostic criteria.
“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
Specific clinical phenotypes commonly associated with Alzheimer's disease pathology are the amnestic syndrome of the hippocampal type, posterior cortical atrophy variant, and logopenic variant primary progressive aphasia.
“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]
Speech and language assessments are useful for diagnosing aphasic syndromes and for characterizing other neurodegenerative disorders.
“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]
Speech and language impairments are the most salient feature in all persons with primary progressive aphasia.
“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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“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].”
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“phenotypes) are: the amnestic syndrome of the hippocampal type 66 (typical), the posterior cortical atrophy variant 67 , and the logopenic variant primary progressive aphasia 68,69 (Supplementary Figure 1).”
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Self-citationFrontotemporal lobar degeneration
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“…dementia can lead to greater carer burden and depression than Alzheimer’s disease (Mioshi et al., 2009; Nunnemann et al., 2012), and lack of support is more concerning for these carers especially when behavioral symptoms are severe (Gorno-Tempini et al., 2011; Rascovsky et al., 2011).”
Background
- 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 › 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
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.
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