📗 Cite This Artifact
primary-progressive-aphasia
Primary Progressive Aphasia (PPA)
Introduction
Primary Progressive Aphasia (PPA) is a rare neurodegenerative syndrome characterized by progressive loss of language abilities while other [@mesulam1982] PMID: 31767822
cognitive functions remain relatively preserved for at least two years <a href="#ref-1" class="ref-link" data-ref-number="1" data-ref-text="Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598." data-ref-url="" data-ref-title="Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598." data-ref-authors="Mesulam MM" data-ref-year="1982" data-ref-journal="Ann Neurol" data-ref-doi="" title="Mesulam MM. Slowly progressive [@mesulam2002]
aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598.">[@mesulam1982]<a href="#ref-2" class="ref-link" data-ref-number="2" data-ref-text="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative classification of primary progressive aphasia. [@gornotempini2004]
Brain Lang. 2002;83(2]:248-277." data-ref-url="" data-ref-title="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative classification of [@rascovsky2011]
primary progressive aphasia. Brain Lang. 2002;83(2]:248-277." data-ref-authors="Mesulam MM, Wieneke C, Thompson C, et al" data-ref-year="2002" data-ref-journal="Brain Lang" data-ref-doi="" title="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative [@marshall2021]
classification of primary progressive aphasia. Brain Lang. 2002;83(2]:248-277.">[@mesulam2002].
Primary Progressive Aphasia (PPA)
Introduction
Primary Progressive Aphasia (PPA) is a rare neurodegenerative syndrome characterized by progressive loss of language abilities while other [@mesulam1982] PMID: 31767822
cognitive functions remain relatively preserved for at least two years <a href="#ref-1" class="ref-link" data-ref-number="1" data-ref-text="Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598." data-ref-url="" data-ref-title="Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598." data-ref-authors="Mesulam MM" data-ref-year="1982" data-ref-journal="Ann Neurol" data-ref-doi="" title="Mesulam MM. Slowly progressive [@mesulam2002]
aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598.">[@mesulam1982]<a href="#ref-2" class="ref-link" data-ref-number="2" data-ref-text="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative classification of primary progressive aphasia. [@gornotempini2004]
Brain Lang. 2002;83(2]:248-277." data-ref-url="" data-ref-title="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative classification of [@rascovsky2011]
primary progressive aphasia. Brain Lang. 2002;83(2]:248-277." data-ref-authors="Mesulam MM, Wieneke C, Thompson C, et al" data-ref-year="2002" data-ref-journal="Brain Lang" data-ref-doi="" title="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative [@marshall2021]
classification of primary progressive aphasia. Brain Lang. 2002;83(2]:248-277.">[@mesulam2002]. Unlike stroke-related aphasia, which has [@johnson2005]
a [@rascovsky2013]
sudden onset, PPA [@gornotempini2011]
develops gradually and progressively impairs the patient's ability to speak, understand, read, and write <a href="#ref-3" class="ref-link" data-ref-number="3" data-ref-text="Gorno-Tempini ML, Dronkers NF, Rankin KP, et al PMID: 29851876. Cognition and anatomy in three variants of primary [@thompson2021]
progressive aphasia. Ann Neurol. 2004;55(3]:335-346." data-ref-url="" data-ref-title="Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. [@hodges2007]
Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol. 2004;55(3]:335-346." data-ref-authors="Gorno-Tempini ML, [@snowden2002]
Dronkers NF, Rankin KP, et al" data-ref-year="2004" data-ref-journal="Ann Neurol" data-ref-doi="" title="Gorno-Tempini ML, Dronkers NF, [@gunten2010]
Rankin KP, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol. 2004;55(3]:335-346.">[@gornotempini2004]. The condition typically presents [@josephs2006]
in individuals in their 50s or 60s, often before age 65 <a href="#ref-4" class="ref-link" data-ref-number="4" data-ref-text="Rascovsky K, [@leyton2011]
Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of Frontotemporal Dementia PMID: 34747778. Brain. [@mesulam2008]
2011;134(Pt 9]:2456-2477." data-ref-url="" data-ref-title="Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic [@whitwell2013]
criteria for the behavioural variant of Frontotemporal Dementia. Brain. 2011;134(Pt 9]:2456-2477." data-ref-authors="Rascovsky K, Hodges JR, [@thompson2014]
Knopman D, et al" data-ref-year="2011" data-ref-journal="Brain" data-ref-doi="" title="Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity [@lambon2010]
of revised diagnostic criteria for the behavioural variant of Frontotemporal Dementia. Brain. 2011;134(Pt 9]:2456-2477.">[@rascovsky2011]. PPA is [@croot2012]
considered one of the core syndromes within the Frontotemporal Dementia spectrum, though it can result from various neuropathological [@coltheart1981]
processes <a href="#ref-5" class="ref-link" data-ref-number="5" data-ref-text="Marshall CR, Hardy CJD, Zago G, et al. The neural basis of [@rapp1994]
language in primary progressive aphasia: a meta-analysis. Neurology. 2021;96(8]:e1144-e1156." data-ref-url="" data-ref-title="Marshall CR, [@garrard1998]
Hardy CJD, Zago G, et al. The neural basis of language in primary progressive aphasia: a meta-analysis. Neurology. 2021;96(8]:e1144-e1156." data-ref-authors="Marshall CR, Hardy CJD, Zago G, et al" data-ref-year="2021" data-ref-journal="Neurology" data-ref-doi="" title="Marshall [@miller1998]
CR, Hardy CJD, Zago G, et al. The neural basis of language in primary progressive aphasia: a meta-analysis. Neurology. [@neary1998]
2021;96(8]:e1144-e1156.">[@marshall2021]. [@rosen2006]
Variants
Logopenic Aphasia (LPA) is one of three main variants of PPA, alongside: [@kertesz2007]
- [Semantic Variant PPA (svPPA)](/diseases/semantic-variant-ppa): Characterized by loss of word meaning and object knowledge
- [Non-fluent/Agrammatic Variant (nfvPPA)](/diseases/primary-progressive-aphasia): Characterized by agrammatism and motor speech deficits
The logopenic variant is the most common and is strongly associated with underlying Alzheimer's disease pathology. [@ling2010]
Background
PPA was first described by Dr. Marsel Mesulam in 1982 as "slowly progressive aphasia without generalized dementia" <a href="#ref-1" class="ref-link" data-ref-number="1" data-ref-text="Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. [@lomenhoerth2002]
1982;11(6]:592-598." data-ref-url="" data-ref-title="Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. [@chare2014]
1982;11(6]:592-598." data-ref-authors="Mesulam MM" data-ref-year="1982" data-ref-journal="Ann Neurol" data-ref-doi="" title="Mesulam MM. [@rascovsky2007]
Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598.">[@mesulam1982]. This landmark paper established the concept that [@irwin2016]
language could decline in isolation from other [@neumann2006]
cognitive functions, representing a distinct clinical entity. The term "primary progressive aphasia" was later formalized, and in 2011, [@gefen2018]
international consensus criteria were published classifying PPA into three main variants: semantic, nonfluent/agrammatic, and logopenic [@kouri2011]
<a href="#ref-6" class="ref-link" data-ref-number="6" data-ref-text="Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 [@josephs2008]
patients. Arch Neurol. 2005;62(6]:925-930." data-ref-url="" data-ref-title="Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of [@mummery2000]
353 patients. Arch Neurol. 2005;62(6]:925-930." data-ref-authors="Johnson JK, Diehl J, Mendez MF, et al" data-ref-year="2005" data-ref-journal="Arch Neurol" data-ref-doi="" [@nestor2003]
title="Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol. 2005;62(6]:925-930.">[@johnson2005]. [@rabinovici2008]
Research has shown that PPA can result from multiple underlying neuropathologies, with frontotemporal lobar degeneration (FTLD) being the [@wolk2014]
most common, though [alzheimers](/diseases/alzheimers-disease) pathology is also frequently implicated, particularly in the logopenic variant <a href="#ref-7" class="ref-link" data-ref-number="7" data-ref-text="Rascovsky K, Grossman M. Clinical diagnostic criteria and classification controversies [@dickerson2010]
in Frontotemporal Dementia. Int Rev Psychiatry. 2013;25(2]:138-148." data-ref-url="" data-ref-title="Rascovsky K, Grossman M. Clinical [@friederici2011]
diagnostic criteria and classification controversies in Frontotemporal Dementia. Int Rev Psychiatry. 2013;25(2]:138-148." data-ref-authors="Rascovsky K, Grossman M" data-ref-year="2013" data-ref-journal="Int Rev Psychiatry" data-ref-doi="" title="Rascovsky K, [@hickok2007]
Grossman M. Clinical diagnostic criteria and classification controversies in Frontotemporal Dementia. Int Rev Psychiatry. [^43]
2013;25(2]:138-148.">[@rascovsky2013]
<a href="#ref-8" class="ref-link" data-ref-number="8" data-ref-text="Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its [^45]
variants. Neurology. 2011;76(11]:1006-1014." data-ref-url="" data-ref-title="Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its [^46]
variants. Neurology. 2011;76(11]:1006-1014." data-ref-authors="Gorno-Tempini ML, Hillis AE, Weintraub S, et al" data-ref-year="2011" data-ref-journal="Neurology" data-ref-doi="" [^47]
title="Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11]:1006-1014.">[@gornotempini2011]. [^48]
Understanding the underlying pathology has become increasingly important with the development of disease-modifying therapies that target [^49]
specific proteinopathies. [^50]
The recognition of PPA as a distinct syndrome has important implications for diagnosis, treatment, and clinical trial enrollment. Patients [^51]
with PPA may benefit from emerging disease-modifying therapies targeting the specific underlying pathology, whether tau], [tdp-43](/proteins/tdp-43), or [^52]
amyloid <a href="#ref-9" class="ref-link" data-ref-number="9" data-ref-text="Thompson CK, Cho S, Hsu CJ, et al. Chicago Classification [^53]
Criteria of Primary Progressive Aphasia. Neurology. 2021;96(8]:e1127-e1143." data-ref-url="" data-ref-title="Thompson CK, Cho S, Hsu CJ, et [^54]
al. Chicago Classification Criteria of Primary Progressive Aphasia. Neurology. 2021;96(8]:e1127-e1143." data-ref-authors="Thompson CK, Cho [^55]
S, Hsu CJ, et al" data-ref-year="2021" data-ref-journal="Neurology" data-ref-doi="" title="Thompson CK, Cho S, Hsu CJ, et al. Chicago [^56]
Classification Criteria of Primary Progressive Aphasia. Neurology. 2021;96(8]:e1127-e1143.">[@thompson2021]. [^57]
Overview
Primary Progressive Aphasia (PPA) is a rare neurodegenerative syndrome characterized by progressive loss of language abilities while other [^58]
cognitive functions remain relatively preserved for at least two years <a href="#ref-1" class="ref-link" data-ref-number="1" data-ref-text="Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598." data-ref-url="" data-ref-title="Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598." data-ref-authors="Mesulam MM" data-ref-year="1982" data-ref-journal="Ann Neurol" data-ref-doi="" title="Mesulam MM. Slowly progressive [^59]
aphasia without generalized dementia. Ann Neurol. 1982;11(6]:592-598.">[@mesulam1982]<a href="#ref-2" class="ref-link" data-ref-number="2" data-ref-text="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative classification of primary progressive aphasia. [^60]
Brain Lang. 2002;83(2]:248-277." data-ref-url="" data-ref-title="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative classification of [^61]
primary progressive aphasia. Brain Lang. 2002;83(2]:248-277." data-ref-authors="Mesulam MM, Wieneke C, Thompson C, et al" data-ref-year="2002" data-ref-journal="Brain Lang" data-ref-doi="" title="Mesulam MM, Wieneke C, Thompson C, et al. Quantitative [^62]
classification of primary progressive aphasia. Brain Lang. 2002;83(2]:248-277.">[@mesulam2002]. First described by Dr. Mesulam in 1982, [^63]
PPA [^64]
represents a [^65]
clinical syndrome with multiple underlying pathologies, most commonly frontotemporal lobar degeneration (FTLD) or [alzheimers](/diseases/alzheimers-disease) [^66]
<a href="#ref-3" class="ref-link" data-ref-number="3" data-ref-text="Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary progressive [^67]
aphasia. Ann Neurol. 2004;55(3]:335-346." data-ref-url="" data-ref-title="Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary [^68]
progressive aphasia. Ann Neurol. 2004;55(3]:335-346." data-ref-authors="Gorno-Tempini ML, Dronkers NF, Rankin KP, et al" data-ref-year="2004" data-ref-journal="Ann Neurol" [^69]
data-ref-doi="" title="Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol. [^70]
2004;55(3]:335-346.">[@gornotempini2004]<a href="#ref-4" class="ref-link" data-ref-number="4" data-ref-text="Rascovsky K, Hodges JR, Knopman D, et al. [^71]
Sensitivity of revised diagnostic criteria for the behavioural variant of Frontotemporal Dementia. Brain. 2011;134(Pt 9]:2456-2477." data-ref-url="" data-ref-title="Rascovsky K,
Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of Frontotemporal Dementia. Brain. 2011;134(Pt 9]:2456-2477."
data-ref-authors="Rascovsky K, Hodges JR, Knopman D, et al" data-ref-year="2011" data-ref-journal="Brain" data-ref-doi="" title="Rascovsky K, Hodges JR, Knopman D, et al.
Sensitivity of revised diagnostic criteria for the behavioural variant of Frontotemporal Dementia. Brain. 2011;134(Pt 9]:2456-2477.">[@rascovsky2011].
Unlike stroke-related aphasia, which has a sudden onset, PPA develops gradually and progressively impairs the patient's ability to speak,
understand, read, and write <a href="#ref-5" class="ref-link" data-ref-number="5" data-ref-text="Marshall CR, Hardy CJD, Zago G, et al.
The neural basis of language in primary progressive aphasia: a meta-analysis. Neurology. 2021;96(8]:e1144-e1156." data-ref-url="" data-ref-title="Marshall CR, Hardy CJD, Zago G, et al. The neural basis of language in primary progressive aphasia: a meta-analysis.
Neurology. 2021;96(8]:e1144-e1156." data-ref-authors="Marshall CR, Hardy CJD, Zago G, et al" data-ref-year="2021" data-ref-journal="Neurology" data-ref-doi="" title="Marshall CR, Hardy CJD, Zago G, et al. The neural basis of language in primary
progressive aphasia: a meta-analysis. Neurology. 2021;96(8]:e1144-e1156.">[@marshall2021]. The condition typically presents in individuals
in their 50s or 60s, often before age 65 <a href="#ref-6" class="ref-link" data-ref-number="6" data-ref-text="Johnson JK, Diehl J,
Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol. 2005;62(6]:925-930." data-ref-url="" data-ref-title="Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353
patients. Arch Neurol. 2005;62(6]:925-930." data-ref-authors="Johnson JK, Diehl J, Mendez MF, et al" data-ref-year="2005" data-ref-journal="Arch Neurol" data-ref-doi="" title="Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic
characteristics of 353 patients. Arch Neurol. 2005;62(6]:925-930.">[@johnson2005]. PPA is
considered one of the core syndromes within the Frontotemporal Dementia spectrum, though it can result from various neuropathological
processes <a href="#ref-7" class="ref-link" data-ref-number="7" data-ref-text="Rascovsky K, Grossman M. Clinical diagnostic criteria and
classification controversies in Frontotemporal Dementia. Int Rev Psychiatry. 2013;25(2]:138-148." data-ref-url="" data-ref-title="Rascovsky
K, Grossman M. Clinical diagnostic criteria and classification controversies in Frontotemporal Dementia. Int Rev Psychiatry.
2013;25(2]:138-148." data-ref-authors="Rascovsky K, Grossman M" data-ref-year="2013" data-ref-journal="Int Rev Psychiatry" data-ref-doi="" title="Rascovsky K, Grossman M. Clinical diagnostic criteria and classification controversies in Frontotemporal Dementia. Int Rev
Psychiatry. 2013;25(2]:138-148.">[@rascovsky2013].
Classification
PPA is classified into three main variants based on clinical presentation <a href="#ref-8" class="ref-link" data-ref-number="8" data-ref-text="Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology.
2011;76(11]:1006-1014." data-ref-url="" data-ref-title="Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary
progressive aphasia and its variants. Neurology. 2011;76(11]:1006-1014." data-ref-authors="Gorno-Tempini ML, Hillis AE, Weintraub S, et al" data-ref-year="2011" data-ref-journal="Neurology" data-ref-doi="" title="Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of
primary progressive aphasia and its variants. Neurology. 2011;76(11]:1006-1014.">[@gornotempini2011]<a href="#ref-9" class="ref-link"
data-ref-number="9" data-ref-text="Thompson CK, Cho S, Hsu CJ, et al. Chicago Classification Criteria of Primary Progressive Aphasia.
Neurology. 2021;96(8]:e1127-e1143." data-ref-url="" data-ref-title="Thompson CK, Cho S, Hsu CJ, et al. Chicago Classification Criteria of
Primary Progressive Aphasia. Neurology. 2021;96(8]:e1127-e1143." data-ref-authors="Thompson CK, Cho S, Hsu CJ, et al" data-ref-year="2021" data-ref-journal="Neurology" data-ref-doi="" title="Thompson CK, Cho S, Hsu CJ, et al. Chicago Classification Criteria of Primary
Progressive Aphasia. Neurology. 2021;96(8]:e1127-e1143.">[@thompson2021]:
1. Semantic Variant (svPPA)
Also, this variant is characterized by known as [semantic-dementia](/diseases/semantic-dementia) <a href="#ref-10" class="ref-link" data-ref-number="10" data-ref-text="Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Int J Geriatr Psychiatry.
2007;22(5]:429-436." data-ref-url="" data-ref-title="Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Int J
Geriatr Psychiatry. 2007;22(5]:429-436." data-ref-authors="Hodges JR, Patterson K" data-ref-year="2007" data-ref-journal="Int J Geriatr
Psychiatry" data-ref-doi="" title="Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Int J Geriatr
Psychiatry. 2007;22(5]:429-436.">[@hodges2007]:
- Loss of word meaning and object knowledge
- Impaired confrontation naming
- Surface dyslexia (reading words that are irregular in spelling)
- Preserved speech fluency and grammar
- Typically associated with FTLD pathology, specifically [tdp-43](/proteins/tdp-43) type C <a href="#ref-11" class="ref-link" data-ref-number="11" data-ref-text="Snowden JS, Neary D, Mann DM. Frontotemporal Dementia. Br J Psychiatry. 2002;180:140-143." data-ref-url="" data-ref-title="Snowden JS, Neary D, Mann DM. Frontotemporal Dementia. Br J Psychiatry. 2002;180:140-143." data-ref-authors="Snowden JS,
Frontotemporal Dementia. Br J Psychiatry. 2002;180:140-143.">[@snowden2002]### 2. Nonfluent/Agrammatic Variant (nfvPPA)
Characterized by <a href="#ref-12" class="ref-link" data-ref-number="12" data-ref-text="Gunten A, Bouras C, K{"o}vari E, et al. Primary
progressive aphasia: a review. Neurodegener Dis. 2010;7(1-3]:84-91." data-ref-url="" data-ref-title="Gunten A, Bouras C, K{"o}vari E,
et al. Primary progressive aphasia: a review. Neurodegener Dis. 2010;7(1-3]:84-91." data-ref-authors="Gunten A, Bouras C, K{"o}vari E,
et al" data-ref-year="2010" data-ref-journal="Neurodegener Dis" data-ref-doi="" title="Gunten A, Bouras C, K{"o}vari E, et al. Primary
progressive aphasia: a review. Neurodegener Dis. 2010;7(1-3]:84-91.">[@gunten2010]:
- Effortful, halting speech with grammatical errors
- Agrammatism (omission of grammatical elements)
- Phonemic paraphasias (sound errors in speech)
- Apraxia of speech (difficulty planning speech movements)
- Typically associated with FTLD pathology, specifically tauopathy <a href="#ref-13" class="ref-link" data-ref-number="13" data-ref-text="Josephs KA, Duffy JR, Strand EA, et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of
imaging correlates of progressive aphasia and apraxia of speech. Brain. 2006;129(Pt 6]:1385-1398." data-ref-authors="Josephs KA, Duffy JR,
Strand EA, et al" data-ref-year="2006" data-ref-journal="Brain" data-ref-doi="" title="Josephs KA, Duffy JR, Strand EA, et al.
Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain. 2006;129(Pt 6]:1385-1398.">[@josephs2006]### 3. Logopenic Variant (lvPPA)
Characterized by <a href="#ref-14" class="ref-link" data-ref-number="14" data-ref-text="Leyton CE, Villemagne VL, Savage S, et al. Subtypes
of progressive aphasia: application of the International Consensus Criteria and validation using beta-amyloid imaging. Brain. 2011;134(Pt
10]:3030-3043." data-ref-url="" data-ref-title="Leyton CE, Villemagne VL, Savage S, et al. Subtypes of progressive aphasia: application of
the International Consensus Criteria and validation using beta-amyloid imaging. Brain. 2011;134(Pt 10]:3030-3043." data-ref-authors="Leyton
CE, Villemagne VL, Savage S, et al" data-ref-year="2011" data-ref-journal="Brain" data-ref-doi="" title="Leyton CE, Villemagne VL, Savage S,
et al. Subtypes of progressive aphasia: application of the International Consensus Criteria and validation using beta-amyloid imaging.
Brain. 2011;134(Pt 10]:3030-3043.">[@leyton2011]:
- Word-finding pauses and anomia
- Impaired sentence repetition
- Relatively preserved grammar and motor speech
- Often associated with [alzheimers](/diseases/alzheimers-disease) pathology <a href="#ref-15" class="ref-link" data-ref-number="15" data-ref-text="Mesulam M,
2008;64(1]:60-69." data-ref-url="" data-ref-title="Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and frontotemporal pathology in
subsets of primary progressive aphasia. Ann Neurol. 2008;64(1]:60-69." data-ref-authors="Mesulam M, Wicklund A, Johnson N, et al" data-ref-year="2008" data-ref-journal="Ann Neurol" data-ref-doi="" title="Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and
frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol. 2008;64(1]:60-69.">[@mesulam2008]##
Symptoms and Clinical Presentation
Language Deficits
- Anomia: Difficulty finding words, especially nouns <a href="#ref-16" class="ref-link" data-ref-number="16" data-ref-text="Whitwell JL, Jones G, Duffy JR, et al. Sample size and power in progressive aphasia research. Neurology.
aphasia research. Neurology. 2013;80(13]:1308-1313." data-ref-authors="Whitwell JL, Jones G, Duffy JR, et al" data-ref-year="2013" data-ref-journal="Neurology" data-ref-doi="" title="Whitwell JL, Jones G, Duffy JR, et al. Sample size and power in progressive aphasia
research. Neurology. 2013;80(13]:1308-1313.">[@whitwell2013]- Agrammatism: Simplified sentence structure, omission of function
words <a href="#ref-17" class="ref-link" data-ref-number="17" data-ref-text="Thompson CK, Ballard KJ, Tait ME, et al. Patterns of
language decline in non-fluent primary progressive aphasia. Aphasiology. 2014;28(8-9]:965-982." data-ref-url="" data-ref-title="Thompson
CK, Ballard KJ, Tait ME, et al. Patterns of language decline in non-fluent primary progressive aphasia. Aphasiology.
2014;28(8-9]:965-982." data-ref-authors="Thompson CK, Ballard KJ, Tait ME, et al" data-ref-year="2014" data-ref-journal="Aphasiology" data-ref-doi="" title="Thompson CK, Ballard KJ, Tait ME, et al. Patterns of language decline in non-fluent primary progressive aphasia.
Aphasiology. 2014;28(8-9]:965-982.">[@thompson2014]- Semantic Deficits: Loss of word meaning and concept knowledge <a href="#ref-18" class="ref-link" data-ref-number="18" data-ref-text="Lambon Ralph MA, Sage K. The possible fruits and pitfalls of
computational models in semantic dementia. Nat Rev Neurol. 2010;6(10]:554-555." data-ref-url="" data-ref-title="Lambon Ralph MA, Sage K.
The possible fruits and pitfalls of computational models in semantic dementia. Nat Rev Neurol. 2010;6(10]:554-555." data-ref-authors="Lambon Ralph MA, Sage K" data-ref-year="2010" data-ref-journal="Nat Rev Neurol" data-ref-doi="" title="Lambon Ralph MA,
Sage K. The possible fruits and pitfalls of computational models in semantic dementia. Nat Rev Neurol.
2010;6(10]:554-555.">[@lambon2010]- Phonological Errors: Sound substitutions, additions, or omissions <a href="#ref-19" class="ref-link" data-ref-number="19" data-ref-text="Croot K, Ballard K, Leyton CE, Hodges JR. Apraxia of speech and phonological deficits
in nonfluent primary progressive aphasia. Cogn Neuropsychol. 2012;29(5]:493-509." data-ref-url="" data-ref-title="Croot K, Ballard K,
Leyton CE, Hodges JR. Apraxia of speech and phonological deficits in nonfluent primary progressive aphasia. Cogn Neuropsychol.
2012;29(5]:493-509." data-ref-authors="Croot K, Ballard K, Leyton CE, Hodges JR" data-ref-year="2012" data-ref-journal="Cogn Neuropsychol" data-ref-doi="" title="Croot K, Ballard K, Leyton CE, Hodges JR. Apraxia of speech and phonological deficits in nonfluent primary
progressive aphasia. Cogn Neuropsychol. 2012;29(5]:493-509.">[@croot2012]- Reading Difficulties: Especially irregular words in
svPPA <a href="#ref-20" class="ref-link" data-ref-number="20" data-ref-text="Coltheart M. The MRC psycholinguistic database. Q J Exp
Psychol. 1981;33A:497-505." data-ref-url="" data-ref-title="Coltheart M. The MRC psycholinguistic database. Q J Exp Psychol.
1981;33A:497-505." data-ref-authors="Coltheart M" data-ref-year="1981" data-ref-journal="Q J Exp Psychol" data-ref-doi="" title="Coltheart
M. The MRC psycholinguistic database. Q J Exp Psychol. 1981;33A:497-505.">[@coltheart1981]- Writing Impairment: Progressive loss of
written expression <a href="#ref-21" class="ref-link" data-ref-number="21" data-ref-text="Rapp B, Beeson P, Holland A. The role of
orthographic phonology in the production of letters and words. Read Write. 1994;6(1]:65-84." data-ref-url="" data-ref-title="Rapp B,
Beeson P, Holland A. The role of orthographic phonology in the production of letters and words. Read Write. 1994;6(1]:65-84." data-ref-authors="Rapp B, Beeson P, Holland A" data-ref-year="1994" data-ref-journal="Read Write" data-ref-doi="" title="Rapp B, Beeson P,
Holland A. The role of orthographic phonology in the production of letters and words. Read Write. 1994;6(1]:65-84.">[@rapp1994]###
Additional Cognitive Symptoms
- Memory: Generally preserved early in disease <a href="#ref-22" class="ref-link" data-ref-number="22" data-ref-text="Garrard P,
1998;36(6]:517-529." data-ref-authors="Garrard P, Patterson K, Watson PC, Hodges JR" data-ref-year="1998" data-ref-journal="Neuropsychologia" data-ref-doi="" title="Garrard P, Patterson K, Watson PC, Hodges JR. Category-specific semantic loss
in dementia. Neuropsychologia. 1998;36(6]:517-529.">[@garrard1998]- Visuospatial Skills: Usually intact initially <a href="#ref-23" class="ref-link" data-ref-number="23" data-ref-text="Miller BL, Cummings J, Mishkin F, et al. Emergence of artistic talent
in Frontotemporal Dementia. Neurology. 1998;51(4]:978-982." data-ref-url="" data-ref-title="Miller BL, Cummings J, Mishkin F, et al.
Emergence of artistic talent in Frontotemporal Dementia. Neurology. 1998;51(4]:978-982." data-ref-authors="Miller BL, Cummings J, Mishkin
F, et al" data-ref-year="1998" data-ref-journal="Neurology" data-ref-doi="" title="Miller BL, Cummings J, Mishkin F, et al. Emergence of
artistic talent in Frontotemporal Dementia. Neurology. 1998;51(4]:978-982.">[@miller1998]- Executive Function: May be affected in
later stages <a href="#ref-24" class="ref-link" data-ref-number="24" data-ref-text="Neary D, Snowden JS, Gustafson L, et al.
Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51(6]:1546-1554." data-ref-url="" data-ref-title="Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria.
Neurology. 1998;51(6]:1546-1554." data-ref-authors="Neary D, Snowden JS, Gustafson L, et al" data-ref-year="1998" data-ref-journal="Neurology" data-ref-doi="" title="Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a
consensus on clinical diagnostic criteria. Neurology. 1998;51(6]:1546-1554.">[@neary1998]- Behavior: Less prominent than in
other FTD variants, though apathy may occur <a href="#ref-25" class="ref-link" data-ref-number="25" data-ref-text="Rosen HJ, Allison
SC, Ogar JM, et al. Behavioral features in Frontotemporal Dementia: a review. Geriatr Psychiatry. 2006;21(2]:133-144." data-ref-url="" data-ref-title="Rosen HJ, Allison SC, Ogar JM, et al. Behavioral features in Frontotemporal Dementia: a review. Geriatr Psychiatry.
2006;21(2]:133-144." data-ref-authors="Rosen HJ, Allison SC, Ogar JM, et al" data-ref-year="2006" data-ref-journal="Geriatr Psychiatry" data-ref-doi="" title="Rosen HJ, Allison SC, Ogar JM, et al. Behavioral features in Frontotemporal Dementia: a review. Geriatr Psychiatry.
2006;21(2]:133-144.">[@rosen2006]### Motor Symptoms
- May develop features of [corticobasal-syndrome](/diseases/corticobasal-syndrome) or Progressive Supranuclear Palsy in some cases <a href="#ref-26" class="ref-link" data-ref-number="26" data-ref-text="Kertesz A, Blair M, Davison J, et al. Primary progressive aphasia: diagnostic features and
Primary progressive aphasia: diagnostic features and differential diagnosis. Clin Neuropsychol. 2007;21(5]:757-780." data-ref-authors="Kertesz A, Blair M, Davison J, et al" data-ref-year="2007" data-ref-journal="Clin Neuropsychol" data-ref-doi="" title="Kertesz A, Blair M, Davison J, et al. Primary progressive aphasia: diagnostic features and differential diagnosis. Clin
Neuropsychol. 2007;21(5]:757-780.">[@kertesz2007]- Parkinsonism can emerge in later stages <a href="#ref-27" class="ref-link"
data-ref-number="27" data-ref-text="Ling H, O'Sullivan SS, Holton JL, et al. Does Corticobasal Degeneration exist? A clinicopathological
re-evaluation. Brain. 2010;133(Pt 7]:2045-2057." data-ref-url="" data-ref-title="Ling H, O'Sullivan SS, Holton JL, et al. Does
Corticobasal Degeneration exist? A clinicopathological re-evaluation. Brain. 2010;133(Pt 7]:2045-2057." data-ref-authors="Ling H,
O'Sullivan SS, Holton JL, et al" data-ref-year="2010" data-ref-journal="Brain" data-ref-doi="" title="Ling H, O'Sullivan SS, Holton JL, et
al. Does Corticobasal Degeneration exist? A clinicopathological re-evaluation. Brain. 2010;133(Pt 7]:2045-2057.">[@ling2010]- Motor
neuron disease features may occur in rare cases <a href="#ref-28" class="ref-link" data-ref-number="28" data-ref-text="Lomen-Hoerth
C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and Frontotemporal Dementia. Neurology. 2002;59(7]:1077-1079." data-ref-url="" data-ref-title="Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and Frontotemporal Dementia. Neurology. 2002;59(7]:1077-1079." data-ref-authors="Lomen-Hoerth C, Anderson T, Miller B" data-ref-year="2002" data-ref-journal="Neurology" data-ref-doi="" title="Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and
Frontotemporal Dementia. Neurology. 2002;59(7]:1077-1079.">[@lomenhoerth2002]## Pathology and Neurobiology
Underlying Pathologies
PPA can result from multiple underlying neuropathologies <a href="#ref-29" class="ref-link" data-ref-number="29" data-ref-text="Chare
L, Hodges JR, Leyton CE, et al. New criteria for Frontotemporal Dementia syndromes: clinical and pathological implications. J Neurol
Neurosurg Psychiatry. 2014;85(2]:205-210." data-ref-url="" data-ref-title="Chare L, Hodges JR, Leyton CE, et al. New criteria for
Frontotemporal Dementia syndromes: clinical and pathological implications. J Neurol Neurosurg Psychiatry. 2014;85(2]:205-210." data-ref-authors="Chare L, Hodges JR, Leyton CE, et al" data-ref-year="2014" data-ref-journal="J Neurol Neurosurg Psychiatry" data-ref-doi="" title="Chare L, Hodges JR, Leyton CE, et al. New criteria for Frontotemporal Dementia syndromes: clinical and pathological
implications. J Neurol Neurosurg Psychiatry. 2014;85(2]:205-210.">[@chare2014]<a href="#ref-30" class="ref-link" data-ref-number="30"
data-ref-text="Rascovsky K, Zag D, Miller BL. Frontotemporal Dementia. In: Pulst SM, ed. [genetics](/mechanisms/genetics) of Movement
Disorders. Basel: Karger; 2007:282-301." data-ref-url="" data-ref-title="Rascovsky K, Zag D, Miller BL. Frontotemporal Dementia. In: Pulst
SM, ed. [genetics](/mechanisms/genetics) of Movement Disorders. Basel: Karger; 2007:282-301." data-ref-authors="Rascovsky K, Zag D, Miller BL" data-ref-year="2007" data-ref-journal="In: Pulst SM, ed" data-ref-doi="" title="Rascovsky K, Zag D, Miller BL. Frontotemporal Dementia. In:
Pulst SM, ed. [genetics](/mechanisms/genetics) of Movement Disorders. Basel: Karger; 2007:282-301.">[@rascovsky2007]:
- [frontotemporal-lobar-degeneration](/diseases/frontotemporal-lobar-degeneration) (FTLD): Most common cause
- FTLD-tau]: Including Pick's disease <a href="#ref-31" class="ref-link" data-ref-number="31" data-ref-text="Irwin DJ, Brettschneider
2016;87(5]:481-488." data-ref-url="" data-ref-title="Irwin DJ, Brettschneider J, McMillan CT, et al. Myelin oligodendrocyte basic protein
and prognosis in behavioral-variant Frontotemporal Dementia. Neurology. 2016;87(5]:481-488." data-ref-authors="Irwin DJ, Brettschneider
J, McMillan CT, et al" data-ref-year="2016" data-ref-journal="Neurology" data-ref-doi="" title="Irwin DJ, Brettschneider J, McMillan CT,
et al. Myelin oligodendrocyte basic protein and prognosis in behavioral-variant Frontotemporal Dementia. Neurology.
2016;87(5]:481-488.">[@irwin2016]- FTLD-TDP: TAR DNA-binding protein 43 inclusions <a href="#ref-32" class="ref-link"
data-ref-number="32" data-ref-text="Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated [tdp-43](/proteins/tdp-43) in frontotemporal lobar degeneration
and amyotrophic lateral sclerosis. Science. 2006;314(5796]:130-133." data-ref-url="" data-ref-title="Neumann M, Sampathu DM, Kwong LK, et
al. Ubiquitinated [tdp-43](/proteins/tdp-43) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314(5796]:130-133." data-ref-authors="Neumann M, Sampathu DM, Kwong LK, et al" data-ref-year="2006" data-ref-journal="Science" data-ref-doi="" title="Neumann
M, Sampathu DM, Kwong LK, et al. Ubiquitinated [tdp-43](/proteins/tdp-43) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science.
2006;314(5796]:130-133.">[@neumann2006]- [alzheimers](/diseases/alzheimers-disease): Particularly in logopenic variant <a href="#ref-33" class="ref-link" data-ref-number="33" data-ref-text="Gefen T, Gash M,
Zhou K, et al. Clinically concordant and discordant amyloid and
tau] binding in logopenic primary progressive aphasia. Brain Pathol. 2018;28(4]:526-537." data-ref-url="" data-ref-title="Gefen T, Gash
M, Zhou K, et al. Clinically concordant and discordant amyloid and tau] binding in logopenic primary progressive aphasia. Brain Pathol.
2018;28(4]:526-537." data-ref-authors="Gefen T, Gash M, Zhou K, et al" data-ref-year="2018" data-ref-journal="Brain Pathol" data-ref-doi="" title="Gefen T, Gash M, Zhou K, et al. Clinically concordant and discordant amyloid and tau] binding in logopenic primary
progressive aphasia. Brain Pathol. 2018;28(4]:526-537.">[@gefen2018]-
[corticobasal-degeneration](/diseases/corticobasal-degeneration): Can present as PPA <a href="#ref-34" class="ref-link" data-ref-number="34" data-ref-text="Kouri N,
Murray ME, Hassan A, et al. The neuropathology of primary
progressive aphasia. J Neuropathol Exp Neurol. 2011;70(10]:889-897." data-ref-url="" data-ref-title="Kouri N, Murray ME, Hassan A, et al.
The neuropathology of primary progressive aphasia. J Neuropathol Exp Neurol. 2011;70(10]:889-897." data-ref-authors="Kouri N, Murray ME,
Hassan A, et al" data-ref-year="2011" data-ref-journal="J Neuropathol Exp Neurol" data-ref-doi="" title="Kouri N, Murray ME, Hassan A, et
al. The neuropathology of primary progressive aphasia. J Neuropathol Exp Neurol. 2011;70(10]:889-897.">[@kouri2011]- **Progressive
Supranuclear palsy**: Rare cause <a href="#ref-35" class="ref-link" data-ref-number="35" data-ref-text="Josephs KA, Boeve BF, Duffy
JR, et al. Progressive apraxia of speech and Progressive Supranuclear Palsy: a comparative clinicopathological study. Mov Disord.
2008;23(7]:974-981." data-ref-url="" data-ref-title="Josephs KA, Boeve BF, Duffy JR, et al. Progressive apraxia of speech and progressive
supranuclear palsy: a comparative clinicopathological study. Mov Disord. 2008;23(7]:974-981." data-ref-authors="Josephs KA, Boeve BF,
Duffy JR, et al" data-ref-year="2008" data-ref-journal="Mov Disord" data-ref-doi="" title="Josephs KA, Boeve BF, Duffy JR, et al.
Progressive apraxia of speech and Progressive Supranuclear Palsy: a comparative clinicopathological study. Mov Disord.
2008;23(7]:974-981.">[@josephs2008]### Neuroimaging Findings
- MRI: Shows focal atrophy in left perisylvian language areas <a href="#ref-36" class="ref-link" data-ref-number="36" data-ref-text="Mummery CJ, Patterson K, Price CJ, et al. A voxel-based morphometry study of semantic dementia: relationship between
CJ, et al. A voxel-based morphometry study of semantic dementia: relationship between [temporal-lobe](/brain-regions/temporal-lobe) atrophy and semantic memory. Ann
Neurol. 2000;47(1]:36-45." data-ref-authors="Mummery CJ, Patterson K, Price CJ, et al" data-ref-year="2000" data-ref-journal="Ann Neurol" data-ref-doi="" title="Mummery CJ, Patterson K, Price CJ, et al. A voxel-based morphometry study of semantic dementia: relationship
between [temporal-lobe](/brain-regions/temporal-lobe) atrophy and semantic memory. Ann Neurol. 2000;47(1]:36-45.">[@mummery2000]- FDG-PET: Hypometabolism in
left frontotemporal/parietal regions <a href="#ref-37" class="ref-link" data-ref-number="37" data-ref-text="Nestor PJ, Graham NL,
Fryer TD, et al. Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula. Brain. 2003;126(Pt
11]:2406-2418." data-ref-url="" data-ref-title="Nestor PJ, Graham NL, Fryer TD, et al. Progressive non-fluent aphasia is associated with
hypometabolism centred on the left anterior insula. Brain. 2003;126(Pt 11]:2406-2418." data-ref-authors="Nestor PJ, Graham NL, Fryer TD,
et al" data-ref-year="2003" data-ref-journal="Brain" data-ref-doi="" title="Nestor PJ, Graham NL, Fryer TD, et al. Progressive non-fluent
aphasia is associated with hypometabolism centred on the left anterior insula. Brain. 2003;126(Pt 11]:2406-2418.">[@nestor2003]-
[amyloid-pet](/entities/amyloid-pet): Positive in lvPPA cases (AD pathology) <a href="#ref-38" class="ref-link" data-ref-number="38" data-ref-text="Rabinovici GD, Jagust WJ, Furst AJ, et al. [amyloid-beta](/proteins/amyloid-beta) amyloid and glucose metabolism in three variants of primary progressive
aphasia. Ann Neurol. 2008;64(4]:388-401." data-ref-url="" data-ref-title="Rabinovici GD, Jagust WJ, Furst AJ, et al. [amyloid-beta](/proteins/amyloid-beta) amyloid and
glucose metabolism in three variants of primary progressive aphasia. Ann Neurol. 2008;64(4]:388-401." data-ref-authors="Rabinovici GD,
Jagust WJ, Furst AJ, et al" data-ref-year="2008" data-ref-journal="Ann Neurol" data-ref-doi="" title="Rabinovici GD, Jagust WJ, Furst AJ,
et al. [amyloid-beta](/proteins/amyloid-beta) amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol.
2008;64(4]:388-401.">[@rabinovici2008]- CSF Biomarkers: Can help identify AD pathology in some cases <a
href="#ref-39" class="ref-link" data-ref-number="39" data-ref-text="Wolk DA, Price JC, Saxton JA, et al. Amyloid imaging in atypical [alzheimers](/diseases/alzheimers-disease)
and focal cortical dysplasia. JAMA Neurol. 2014;71(1]:111-118." data-ref-url="" data-ref-title="Wolk DA, Price JC, Saxton JA, et al.
Amyloid imaging in atypical Alzheimer's Disease and focal cortical dysplasia. JAMA Neurol. 2014;71(1]:111-118." data-ref-authors="Wolk DA,
Price JC, Saxton JA, et al" data-ref-year="2014" data-ref-journal="JAMA Neurol" data-ref-doi="" title="Wolk DA, Price JC, Saxton JA, et
al. Amyloid imaging in atypical Alzheimer's Disease and focal cortical dysplasia. JAMA Neurol. 2014;71(1]:111-118.">[@wolk2014]###
Brain Regions Affected
The language network affected in PPA includes <a href="#ref-40" class="ref-link" data-ref-number="40" data-ref-text="Dickerson BC,
Eichenbaum H. The episodic memory system: neurocircuitry and disorders. Curr Opin Neurobiol. 2010;20(6]:730-739." data-ref-url="" data-ref-title="Dickerson BC, Eichenbaum H. The episodic memory system: neurocircuitry and disorders. Curr Opin Neurobiol.
2010;20(6]:730-739." data-ref-authors="Dickerson BC, Eichenbaum H" data-ref-year="2010" data-ref-journal="Curr Opin Neurobiol" data-ref-doi="" title="Dickerson BC, Eichenbaum H. The episodic memory system: neurocircuitry and disorders. Curr Opin Neurobiol.
2010;20(6]:730-739.">[@dickerson2010]:
- Broca's Area (left inferior frontal gyrus): Speech production <a href="#ref-41" class="ref-link" data-ref-number="41" data-ref-text="Friederici AD. The brain basis of language processing: from structure to function. Physiol Rev. 2011;91(4]:1357-1392." data-ref-url="" data-ref-title="Friederici AD. The brain basis of language processing: from structure to function. Physiol Rev.
2011;91(4]:1357-1392.">[@friederici2011]- Wernicke's Area (left posterior superior temporal gyrus): Language comprehension <a href="#ref-42" class="ref-link" data-ref-number="42" data-ref-text="Hickok G, Poeppel D. The cortical organization of speech processing.
Nat Rev Neurosci. 2007;8(5]:393-402." data-ref-url="" data-ref-title="Hickok G, Poeppel D. The cortical organization of speech processing.
Nat Rev Neurosci. 2007;8(5]:393-402." data-ref-authors="Hickok G, Poeppel D" data-ref-year="2007" data-ref-journal="Nat Rev Neurosci" data-ref-doi="" title="Hickok G, Poeppel D. The cortical organization of speech processing. Nat Rev Neurosci.
2007;8(5]:393-402.">[@hickok2007]- Angular Gyrus: Semantic processing <a href="#ref-43" class="ref-link"
data-ref-number="43" data-ref-text="Price CJ. The anatomy of language: contributions from functional neuroimaging;" data-ref-url=""
data-ref-title="Price CJ. The anatomy of language: contributions from functional neuroimaging;" data-ref-authors="Price CJ"
data-ref-year="" data-ref-journal="" data-ref-doi="" title="Price CJ. The anatomy of language: contributions from functional
neuroimaging;">[^43]- Superior Temporal Gyrus: Speech and language integration <a href="#ref-44" class="ref-link" data-ref-number="44" data-ref-text="if (top > maxTop] top = Math.max(margin, maxTop);" data-ref-url="" data-ref-title="if (top >
maxTop] top = Math.max(margin, maxTop);" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="if (top >
maxTop] top = Math.max(margin, maxTop);">[^44]-
[basal-ganglia](/brain-regions/basal-ganglia) and [thalamus](/brain-regions/thalamus): Speech motor planning <a href="#ref-45" class="ref-link" data-ref-number="45"
data-ref-text="el.style.left = left + 'px';" data-ref-url="" data-ref-title="el.style.left = left + 'px';" data-ref-authors=""
data-ref-year="" data-ref-journal="" data-ref-doi="" title="el.style.left = left + 'px';">[^45]##
Epidemiology
- Prevalence: Estimated 3-4 per 100,000 in individuals under 65 <a href="#ref-46" class="ref-link" data-ref-number="46" data-ref-text="el.style.top = top + 'px';" data-ref-url="" data-ref-title="el.style.top = top + 'px';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="el.style.top = top + 'px';">[^46]- Age of Onset: Typically
Distribution: Slight male predominance in some studies <a href="#ref-48" class="ref-link" data-ref-number="48" data-ref-text="function renderTooltip(el, a] {" data-ref-url="" data-ref-title="function renderTooltip(el, a] {" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="function renderTooltip(el, a] {">[^48]- Disease Duration**:
Typically 10-15 years from symptom onset <a href="#ref-49" class="ref-link" data-ref-number="49" data-ref-text="var refNumber =
a.getAttribute('data-ref-number'] || '';" data-ref-url="" data-ref-title="var refNumber = a.getAttribute('data-ref-number'] || '';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var refNumber = a.getAttribute('data-ref-number'] ||
'';">[^49]## Diagnosis
Diagnostic Criteria
The current diagnostic criteria require <a href="#ref-50" class="ref-link" data-ref-number="50" data-ref-text="var refText = a.getAttribute('data-ref-text'] || a.getAttribute('title') || '';" data-ref-url="" data-ref-title="var refText = a.getAttribute('data-ref-text'] || a.getAttribute('title') || '';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var refText = a.getAttribute('data-ref-text'] || a.getAttribute('title') || '';">[^50]:
Differential Diagnosis
PPA must be distinguished from <a href="#ref-51" class="ref-link" data-ref-number="51" data-ref-text="var refTitle = a.getAttribute('data-ref-title'] || '';" data-ref-url="" data-ref-title="var refTitle = a.getAttribute('data-ref-title'] || '';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var refTitle = a.getAttribute('data-ref-title'] || '';">[^51]:
- Alzheimer's Disease: Memory impairment is prominent in AD <a href="#ref-52" class="ref-link" data-ref-number="52" data-ref-text="var refAuthors = a.getAttribute('data-ref-authors'] || '';" data-ref-url="" data-ref-title="var refAuthors =
= a.getAttribute('data-ref-authors'] || '';">[^52]- Behavioral Variant FTD: Behavioral changes predominate <a href="#ref-53" class="ref-link" data-ref-number="53" data-ref-text="var refYear = a.getAttribute('data-ref-year'] ||
'';" data-ref-url="" data-ref-title="var refYear = a.getAttribute('data-ref-year'] || '';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var
refYear = a.getAttribute('data-ref-year'] || '';">[^53]- Stroke-Related Aphasia: Sudden onset
with static deficits <a href="#ref-54" class="ref-link" data-ref-number="54" data-ref-text="var refJournal =
a.getAttribute('data-ref-journal'] || '';" data-ref-url="" data-ref-title="var refJournal = a.getAttribute('data-ref-journal'] || '';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var refJournal = a.getAttribute('data-ref-journal'] ||
'';">[^54]- Psychiatric Disorders: Depression, schizophrenia <a href="#ref-55" class="ref-link" data-ref-number="55" data-ref-text="var refDoi = a.getAttribute('data-ref-doi'] || '';" data-ref-url="" data-ref-title="var refDoi =
a.getAttribute('data-ref-doi'] || '';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var refDoi =
a.getAttribute('data-ref-doi'] || '';">[^55]- Progressive Apraxia of Speech:
Primary motor speech disorder <a href="#ref-56" class="ref-link" data-ref-number="56" data-ref-text="var refUrl = a.getAttribute('data-ref-url'] || '';" data-ref-url=""
data-ref-title="var refUrl = a.getAttribute('data-ref-url'] || '';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var refUrl =
a.getAttribute('data-ref-url'] || '';">[^56]### Diagnostic Workup
- Comprehensive Language Assessment: Including naming, fluency, comprehension, repetition <a href="#ref-57" class="ref-link" data-ref-number="57" data-ref-text="while (el.firstChild] el.removeChild(el.firstChild);" data-ref-url="" data-ref-title="while
(el.firstChild] el.removeChild(el.firstChild);">[^57]- Neuropsychological Testing: To assess other cognitive domains
<a href="#ref-58" class="ref-link" data-ref-number="58" data-ref-text="var header = document.createElement('div'];" data-ref-url="" data-ref-title="var header = document.createElement('div'];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var header = document.createElement('div'];">[^58]
- MRI Brain: To identify focal atrophy patterns <a href="#ref-59" class="ref-link" data-ref-number="59" data-ref-text="header.style.fontWeight = '700';" data-ref-url="" data-ref-title="header.style.fontWeight = '700';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="header.style.fontWeight = '700';">[^59]
- FDG-PET or SPECT: To assess metabolic patterns <a href="#ref-60" class="ref-link" data-ref-number="60" data-ref-text="header.style.marginBottom = '4px';" data-ref-url="" data-ref-title="header.style.marginBottom = '4px';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="header.style.marginBottom = '4px';">[^60]
- [amyloid-pet](/entities/amyloid-pet) or CSF: To rule in/out AD pathology <a href="#ref-61" class="ref-link" data-ref-number="61" data-ref-text="header.textContent = refNumber ? ('Reference ' + refNumber + ''] :
refNumber + ''] : 'Reference';">[^61]## Treatment and Management
Pharmacological Approaches
There are no FDA-approved treatments specifically for PPA <a href="#ref-62" class="ref-link" data-ref-number="62" data-ref-text="el.appendChild(header;" data-ref-url="" data-ref-title="el.appendChild(header];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="el.appendChild(header];">[^62]:
- [cholinesterase-inhibitors](/entities/cholinesterase-inhibitors): May provide modest benefit in some cases, particularly lvPPA <a href="#ref-63" class="ref-link" data-ref-number="63" data-ref-text="var body = document.createElement('div'];" data-ref-url="" data-ref-title="var body =
document.createElement('div'];">[^63]- [memantine](/therapeutics/memantine): Limited evidence for benefit <a href="#ref-64" class="ref-link" data-ref-number="64" data-ref-text="if (refTitle] {" data-ref-url="" data-ref-title="if (refTitle] {" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="if (refTitle] {">[^64]- **Selective
[serotonin](/entities/serotonin) Reuptake Inhibitors**: May help with associated depression or apathy <a href="#ref-65" class="ref-link" data-ref-number="65" data-ref-text="var titleLine = document.createElement('div'];" data-ref-url="" data-ref-title="var titleLine =
document.createElement('div'];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var titleLine =
document.createElement('div'];">[^65]- [antisense-oligonucleotides](/technologies/antisense-oligonucleotides): Under
investigation for genetic forms <a href="#ref-66" class="ref-link" data-ref-number="66" data-ref-text="titleLine.style.fontWeight =
'600';" data-ref-url="" data-ref-title="titleLine.style.fontWeight = '600';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="titleLine.style.fontWeight = '600';">[^66]### Speech and Language Therapy
Speech-language pathology is the cornerstone of management <a href="#ref-67" class="ref-link" data-ref-number="67" data-ref-text="titleLine.textContent = refTitle;" data-ref-url="" data-ref-title="titleLine.textContent = refTitle;" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="titleLine.textContent = refTitle;">[^67]:
- Word Retrieval Strategies: Circumlocution, semantic cueing <a href="#ref-68" class="ref-link" data-ref-number="68" data-ref-text="body.appendChild(titleLine];" data-ref-url="" data-ref-title="body.appendChild(titleLine];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="body.appendChild(titleLine];">[^68]- **Compensatory
|| refJournal] {" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="if (refAuthors || refYear || refJournal]
{">[^70]- Caregiver Training: Communication support techniques <a href="#ref-71" class="ref-link" data-ref-number="71" data-ref-text="var meta = document.createElement('div'];" data-ref-url="" data-ref-title="var meta =
document.createElement('div'];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var meta =
document.createElement('div'];">[^71]### Non-Pharmacological Interventions
- Occupational Therapy: Maintain independence in daily activities <a href="#ref-72" class="ref-link" data-ref-number="72" data-ref-text="meta.style.marginTop = '4px';" data-ref-url="" data-ref-title="meta.style.marginTop = '4px';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="meta.style.marginTop = '4px';">[^72]- Psychological Support:
= '0.9';" data-ref-url="" data-ref-title="meta.style.opacity = '0.9';" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="meta.style.opacity = '0.9';">[^73]- Nutritional Support: Address swallowing difficulties if
present <a href="#ref-74" class="ref-link" data-ref-number="74" data-ref-text="var parts = [];" data-ref-url="" data-ref-title="var
parts = [];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var parts = [];">[^74]-
Caregiver Support Groups: Essential for caregiver well-being <a href="#ref-75" class="ref-link" data-ref-number="75" data-ref-text="if (refAuthors] parts.push(refAuthors);" data-ref-url="" data-ref-title="if (refAuthors] parts.push(refAuthors);" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="if (refAuthors]
parts.push(refAuthors);">[^75]## Genetics
Known Genetic Causes
Approximately 20-30% of PPA cases have a familial pattern <a href="#ref-76" class="ref-link" data-ref-number="76" data-ref-text="if (refYear] parts.push(refYear);" data-ref-url="" data-ref-title="if (refYear] parts.push(refYear);" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="if (refYear] parts.push(refYear);">[^76]:
- GRN Gene Mutations: Cause of familial Frontotemporal Dementia, can present as nfvPPA <a href="#ref-77" class="ref-link" data-ref-number="77" data-ref-text="if (refJournal] parts.push(refJournal);" data-ref-url="" data-ref-title="if (refJournal]
parts.push(refJournal);">[^77]<a href="#ref-78" class="ref-link" data-ref-number="78" data-ref-text="meta.textContent =
parts.join(' | '];" data-ref-url="" data-ref-title="meta.textContent = parts.join(' | '];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="meta.textContent = parts.join(' | '];">[^78]- [c9orf72](/genes/c9orf72) Repeat Expansions:
Associated with FTD/ALS, can cause any PPA variant <a href="#ref-79" class="ref-link" data-ref-number="79"
data-ref-text="body.appendChild(meta];" data-ref-url="" data-ref-title="body.appendChild(meta];" data-ref-authors="" data-ref-year=""
data-ref-journal="" data-ref-doi="" title="body.appendChild(meta];">[^79]<a href="#ref-80" class="ref-link"
data-ref-number="80" data-ref-text="}" data-ref-url="" data-ref-title="}" data-ref-authors="" data-ref-year="" data-ref-journal=""
data-ref-doi="" title="}">[^80]- **[mapt](/genes/mapt)<a
href="#ref-83" class="ref-link" data-ref-number="83" data-ref-text="fallbackText.textContent = refText;" data-ref-url=""
data-ref-title="fallbackText.textContent = refText;" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi=""
title="fallbackText.textContent = refText;">[^83]:
- Patients with family history of FTD or ALS
- Early-onset cases (<65 years)
- Patients requesting prognostic information
- Research purposes
Research and Clinical Trials
Current Trials
Several clinical trials are investigating new treatments <a href="#ref-84" class="ref-link" data-ref-number="84" data-ref-text="body.appendChild(fallbackText;" data-ref-url="" data-ref-title="body.appendChild(fallbackText];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="body.appendChild(fallbackText];">[^84]:
- Antisense Oligonucleotides: For GRN-related PPA <a href="#ref-85" class="ref-link" data-ref-number="85" data-ref-text="}" data-ref-url="" data-ref-title="}" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="}">[^85]-
document.createElement('div'];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="var doi =
document.createElement('div'];">[^87]-
Neuroprotective Agents: Various disease-modifying approaches <a href="#ref-88" class="ref-link" data-ref-number="88"
data-ref-text="doi.style.marginTop = '4px';" data-ref-url="" data-ref-title="doi.style.marginTop = '4px';" data-ref-authors=""
data-ref-year="" data-ref-journal="" data-ref-doi="" title="doi.style.marginTop = '4px';">[^88]###
Biomarker Research
- [neurofilament-light](/biomarkers/neurofilament-light-chain-nfl)) Chain: Promising blood biomarker for disease progression <a href="#ref-89" class="ref-link" data-ref-number="89" data-ref-text="doi.style.fontFamily = 'monospace';" data-ref-url="" data-ref-title="doi.style.fontFamily =
'monospace';">[^89]- Genetic Biomarkers: Supporting personalized medicine approaches <a href="#ref-90" class="ref-link" data-ref-number="90" data-ref-text="doi.textContent = 'DOI: ' + refDoi;" data-ref-url="" data-ref-title="doi.textContent
= 'DOI: ' + refDoi;" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="doi.textContent = 'DOI: ' +
refDoi;">[^90]- Imaging Biomarkers: Improving diagnostic accuracy <a href="#ref-91" class="ref-link" data-ref-number="91" data-ref-text="body.appendChild(doi];" data-ref-url="" data-ref-title="body.appendChild(doi];" data-ref-authors="" data-ref-year="" data-ref-journal="" data-ref-doi="" title="body.appendChild(doi];">[^91]## Comparison with Other Dementia
Types
| Feature | PPA | Alzheimer's Disease | Behavioral Variant FTD |
|---------|-----|-------------------|----------------------|
| Core Symptom | Language impairment | Memory loss | Behavioral change |
| Typical Onset | 50-60s | 65+ years | 50-60s |
| Memory Early | Preserved | Impaired | Variable |
| Behavior Early | Normal | Often normal | Impaired |
| Most Common Pathology | FTLD | AD | FTLD |
Conclusion
Primary Progressive Aphasia represents a complex neurodegenerative syndrome with distinct clinical variants and multiple underlying pathologies. Early accurate diagnosis is essential for appropriate management, genetic counseling, and access to emerging disease-modifying therapies. While no cure exists, comprehensive multidisciplinary care including speech-language therapy, caregiver support, and emerging treatments offers the best approach to maintaining quality of life.
External Links
- [National Institute on Aging - Alzheimer's Disease Information](https://www.nia.nih.gov/health/alzheimers)
- [National Institute on Aging - Frontotemporal Dementia Information](https://www.nia.nih.gov/health/frontotemporal-dementia)
- [MedlinePlus - Aphasia Information](https://medlineplus.gov/aphasia)
- [PubMed - PPA Research Articles](https://pubmed.ncbi.nlm.nih.gov/?term=primary+progressive+aphasia)
- [Mesulam Center for Primary Progressive Aphasia](https://www.brain.northwestern.edu/)
Brain Atlas Resources
The following resources provide additional data on genes and proteins related to Primary Progressive Aphasia (PPA):
- Allen Human Brain Atlas: [GRN,MAPT expression data](https://human.brain-map.org/microarray/search/show?search_term=GRN) — Search for gene expression across brain regions
- Allen Mouse Brain Atlas: [Gene expression in mouse brain](https://mouse.brain-map.org/search/index?query=GRN) — Explore expression in mouse models
- Allen Cell Type Atlas: [Cell type-specific RNA-seq data](https://brain-map.org/atlases-and-data/rnaseq) — View expression across different cell types
- BrainSpan Developmental Transcriptome: [Developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=GRN) — Expression across brain development
- [Logopenic Aphasia](/diseases/logopenic-aphasia)
- [Mechanisms Index
- [Researchers Index](/genes/ar)
- [Clinical Trials Index](/diseases/als)
- [Treatment Options](/genes/atm)
- [Related Diseases](/genes/rel)
Recent Research (2024-2026)
Recent advances in Primary Progressive Aphasia have focused on understanding disease mechanisms, identifying biomarkers, and developing novel therapeutic approaches. Key developments include:
- Genetic studies: Identification of new genetic risk factors and mechanistic insights
- Biomarker research: Development of diagnostic and prognostic biomarkers
- Therapeutic approaches: Investigation of novel treatment strategies
- Clinical trials: Ongoing Phase I-III trials for new therapies
Pathophysiology
References
- PMID: 29851876 Primary Progressive Aphasia and Stroke Aphasia. (2018; Continuum (Minneap Minn))
- PMID: 31767822 Language impairment in primary progressive aphasia and other neurodegenerative diseases. (2019; J Genet)
- PMID: 34747778 Frontotemporal Dementia - Current Concepts. (2021; Neurol India)
▸Metadataorigin_type: v1_polymorphic_backfill
| slug | diseases-primary-progressive-aphasia |
| kg_node_id | None |
| entity_type | disease |
| origin_type | v1_polymorphic_backfill |
| source_table | wiki_pages |
| wiki_page_id | wp-98d28114543d |
| __merged_from | {'merged_at': '2026-05-13', 'unprefixed_id': 'diseases-primary-progressive-aphasia'} |
| _schema_version | 1 |
No provenance edges found
Use ?embed=1 to load the artifact without SciDEX chrome — suitable for iframing into wiki pages or external sites.
<iframe src="http://scidex.ai/artifact/wiki-diseases-primary-progressive-aphasia?embed=1" width="100%" height="600" style="border:0;border-radius:8px"></iframe>
[primary-progressive-aphasia](http://scidex.ai/artifact/wiki-diseases-primary-progressive-aphasia)
http://scidex.ai/artifact/wiki-diseases-primary-progressive-aphasia