Materiały źródłowe

• #1 Primary Progressive Aphasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563145/

  Aphasia is a language disorder arising from damage to a specific brain area controlling language comprehension, formulation, and expression. Primary progressive aphasia (PPA) refers to a group of neurodegenerative diseases in which gradual speech and language impairment are the primary presenting symptoms, unaccompanied by marked cognitive, physical, or behavioral changes. […] PPA characterization and differentiation based on linguistic and nonlinguistic profiles are now easier to accomplish due to extensive research. Advanced neuroimaging techniques like diffusion-weighted imaging (DWI) and resting-state functional magnetic resonance imaging (fMRI) allow healthcare providers to go beyond distinct focal gray matter atrophy patterns to a deeper understanding of PPA’s effects on structural and functional connectivity changes. However, despite significant diagnostic advances, a clear consensus on its pathology remains elusive.

• #2 Primary Progressive Aphasia | Memory and Aging Center

  https://memory.ucsf.edu/dementia/primary-progressive-aphasia

  Primary progressive aphasia (PPA) is a condition that slowly damages the parts of the brain that control speech and language. […] The clinical symptoms of PPA are caused by degeneration in the parts of the brain that control speech and language (typically the left side of the brain in the frontal, temporal, and parietal regions). […] These syndromes result from a variety of underlying diseases, but frontotemporal lobar degeneration (FTLD) (both tau and TDP-43 subtypes) or Alzheimers disease is most often the cause.

• #3 Primary progressive aphasia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/primary-progressive-aphasia/symptoms-causes/syc-20350499

  Primary progressive aphasia is caused by a shrinking of certain areas of the brain, known as lobes. In primary progressive aphasia, the frontal, temporal or parietal lobes are affected. When areas of the brain shrink, it’s called atrophy. The atrophy caused by primary progressive aphasia mainly happens on the left side of the brain. The areas affected are responsible for speech and language. […] Atrophy is linked to the presence of certain proteins in the brain. The proteins may reduce brain activity or function.

• #4 Primary Progressive Aphasia (PPA): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17387-primary-progressive-aphasia-ppa

  Primary progressive aphasia (PPA) is a neurological disorder that affects a persons ability to speak and communicate. Aphasia is a language disorder that results from damage to key parts of your brain that are responsible for understanding or producing speech and/or writing. […] Most commonly, the underlying cause of PPA is a neurodegenerative disease like Alzheimers disease or frontotemporal dementia. In these conditions, the areas of your brain related to control of speech or understanding of words and their meaning break down. […] Primary progressive aphasia develops when the parts of your brain that control language start breaking down. Your brain tissue shrinks (atrophies), affecting your ability to communicate. Sometimes, this breakdown starts because of a gene mutation that youre born with. Other times, it may happen for no known reason. […] Experts dont always know what causes this condition, but its often a combination of environmental and genetic factors.

• #5 Primary Progressive Aphasia

  https://www.webmd.com/brain/primary-progressive-aphasia

  PPA happens when certain parts of your brain atrophy (shrink). Most of the atrophy in PPA is on the left side of your brain in the frontal, temporal, or parietal lobes. These are the parts of your brain responsible for speech and language. […] Scientists link brain atrophy to the presence of certain proteins tau, TDP-43, or amyloid in your brain. The buildup of these proteins may reduce brain function in these areas, which is how you lose the ability to speak and communicate.

• #6 What is Primary progressive aphasia? – Alzheimer’s Research UK

  https://www.alzheimersresearchuk.org/dementia-information/types-of-dementia/primary-progressive-aphasia/

  Primary progressive aphasia (PPA) is a rare type of dementia. It is caused by damage to parts of the brain that control our language, personality, emotions and behaviour. […] We know that there is an unusual build-up of certain proteins inside brain cells. These proteins include TDP-43 and tau, and researchers are working hard to find out why this happens and how it damages brain cells. […] Different types of PPA often have different protein changes in the brain: Semantic dementia is mainly caused by protein TDP-43; Progressive non-fluent aphasia is most often caused by protein tau; Most cases of logopenic aphasia are caused by the same underlying processes involved in Alzheimer’s disease. This includes the build-up of a protein called amyloid in the brain, which damages brain cells over time. This is why, logopenic aphasia is often called an unusual or “atypical” form of young onset Alzheimer’s.

• #7 Primary Progressive Aphasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563145/

  Pathologically, nfvPPA is grouped under the frontotemporal dementia (FTD) syndromes. In contrast, the logopenic variant is frequently classified as an atypical Alzheimer disease form. […] The pathology underlying svPPA mainly involves the atrophy and hypometabolism of the anterior temporal lobes, particularly the temporal poles, with a notable left-sided predominance. In 80% of cases, svPPA exhibits aggregates of TAR DNA-binding protein 43kDa (TDP-43), similar to the pathological features observed in FTD and amyotrophic lateral sclerosis. […] The pathophysiology of nfvPPA remains under investigation. This condition exhibits more pathology and disease progression variability than other PPA types. However, involvement of the dominant inferior frontal lobe (Broca area) is consistently observed, with atrophy of the insular cortex in the dominant hemisphere also common.

• #8 Primary Progressive Aphasia: Toward a Pathophysiological Synthesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7861583/

  New findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies. […] Here, we argue that these problems might be addressed by an improved pathophysiological understanding of PPA. […] The major molecular histopathological associations differ between the major syndromes of PPA: nfvPPA is most often associated with primary tauopathies, svPPA is closely associated with TDP-43 (type C) pathology, and lvPPA with Alzheimer pathology, leading to the proposal that the PPA may constitute molecular nexopathies. […] Emerging evidence suggests that specific language network vulnerabilities caused by genetic, developmental, and/or lifestyle factors may determine why some people develop a PPA phenotype in the context of a specific proteinopathy.

• #9

  https://link.springer.com/article/10.1007/s11910-021-01097-z

  The term primary progressive aphasia (PPA) refers to a diverse group of dementias that present with prominent and early problems with speech and language. […] New findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies. […] Here, we argue that these problems might be addressed by an improved pathophysiological understanding of PPA. […] One of the most ambitious, but most important, challenges in neurodegenerative disease research is to identify how pathogenic proteins give rise to complex phenotypes. […] The major molecular histopathological associations differ between the major syndromes of PPA: nfvPPA is most often associated with primary tauopathies, svPPA is closely associated with TDP-43 (type C) pathology, and lvPPA with Alzheimer pathology, leading to the proposal that the PPA may constitute molecular nexopathies.

• #10 Primary Progressive Aphasia | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/82030

  PPA is a group of neurodegenerative disorders primarily affecting the language (dominant) areas of the brain. The disorder is usually considered an FTD subtype. Since 2011, FTD has been classified clinically and pathologically into the more common behavioral variant (bvFTD) and primary progressive aphasia (PPA). The 3 PPA variants arise from neurodegenerative changes in different brain areas. The semantic and nonfluent variants are related to FTD, while the logopenic type resembles Alzheimer disease more closely. The semantic variant mainly affects the anterior temporal region. The nonfluent variant impacts the inferior frontal gyrus and precentral cortex regions. The logopenic variant involves the left posterior superior and middle temporal gyri and inferior parietal lobule. […] NfvPPA is most commonly associated with an FTD-4R tau protein form. Other reports indicate TDP-43-A pathology in nfvPPA. Some nfvPPA cases are associated with progranulin (PGRN) or chromosome 9 open reading frame 72 (C9orf72) gene mutations. Less frequently, Alzheimer disease pathology has also been reported in nfvPPA. The 3 genes primarily associated with FTD are microtubule-associated protein tau (MAPT), granulin (GRN), and C9orf72. Frontotemporal lobar degeneration is frequently associated with nfvPPA. Interestingly, prospectively recruited cohorts of PPA suggest mutations are rarely the cause of nfvPPA.

• #11 Primary progressive aphasia involves many losses: Here’s what you need to know – Harvard Health

  https://www.health.harvard.edu/blog/progressive-aphasia-involves-many-losses-heres-what-you-need-to-know-202204132723

  Neurodegenerative diseases are disorders that slowly and relentlessly damage the brain. […] When a neurodegenerative disease causes problems with language first and foremost, it is called primary progressive aphasia. […] The logopenic variant of primary progressive aphasia is usually caused by Alzheimer’s disease. […] The semantic variant of primary progressive aphasia is usually caused by frontotemporal lobar degeneration, and specifically by accumulation of TDP-43. […] The nonfluent/agrammatic variant of primary progressive is also usually caused by frontotemporal lobar degeneration, but this time it is most often due to tau pathology.

• #12 Primary Progressive Aphasia | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/82030

  SvPPA is nearly always associated with underlying TDP-43-C pathological aggregates found in 75-100% of cases in clinicopathological correlation series. This variant is most often associated with FTD tau in the remainder of patients. SvPPA is most consistently associated with left (dominant) temporal lobe pathology. […] LvPPA is most often caused by Alzheimer disease pathology in as many as 95% of cases. This condition is recognized as one of the potential focal and early-onset presentations of Alzheimer disease, although other pathological profiles such as Lewy body dementia, TDP-43, and tau have been less commonly reported. […] The pathology underlying svPPA mainly involves the atrophy and hypometabolism of the anterior temporal lobes, particularly the temporal poles, with a notable left-sided predominance. In 80% of cases, svPPA exhibits aggregates of TAR DNA-binding protein 43kDa (TDP-43), similar to the pathological features observed in FTD and amyotrophic lateral sclerosis.

• #13 Semantic Variant PPA (Primary Progressive Aphasia)| AFTD

  https://www.theaftd.org/what-is-ftd/primary-progressive-aphasia/semantic-variant-ppa-svppa/

  Accumulation of TDP-43 is most commonly found at autopsy insvPPA; the remainder exhibit tau pathology. […] Very rarely, some individuals diagnosed with svPPA during life are revealed to have Alzheimer’s disease pathology at autopsy.

• #14 Primary Progressive Aphasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563145/

  Meanwhile, lvPPA is most commonly an aphasic Alzheimer disease variant. Patients most frequently develop the typical clinical Alzheimer disease features. The pathology is similar to Alzheimer disease but with more left-sided perisylvian or parietal atrophy. Similar to Alzheimer disease, lvPPA also has amyloid and hyperphosphorylated tau accumulation.

• #15

  https://www.brain.northwestern.edu/dementia/primary-progressive-aphasia/symptoms-causes.html

  The symptoms of PPA occur when brain cells malfunction in language-related parts of the brain due to the accumulation of abnormal proteins. […] The underlying diseases causing PPA are called „neurodegenerative” because they cause gradually progressive brain cell death that cannot be attributed to other causes, such as head trauma, infection, stroke or cancer. […] When abnormal proteins from AD or one of the forms of FTLD attack the language areas of the brain, PPA results. PPA is caused by AD in approximately 30 to 40 percent of cases and by one of the forms of FTLD in approximately 60 to 70 percent of cases. […] There is no one-to-one relationship between PPA subtype and underlying pathology. However, PPA-S (semantic variant) is most commonly associated with FTLD-TDP; PPA-G (agrammatic/nonfluent variant) is most commonly FTLD-tau; and PPA-L (logopenic variant) is most commonly associated with AD. These are only probabilities. Better biomarkers are needed to determine the neuropathologic diagnosis for each individual during life.

• #16 Multimodality Imaging in Primary Progressive Aphasia | American Journal of Neuroradiology

  http://www.ajnr.org/content/43/9/1230

  Deposits of TDP-43, a cellular protein encoded by the TARDBP gene and with 4 described subtypes (A, B, C, D), is an additional frequently identified pathologic substrate seen in cases of PPA. […] While trends have been reported between these histopathologic entities and PPA subtypes (lvPPA: AD pathology; svPPA: TDP-43; nfvPPA: 4R-), no absolute association exists and inconsistencies regarding the frequency of molecular alterations for each variant have been described across studies, likely related to varied diagnostic approaches. […] While the aforementioned evidence supports underlying AD pathology in most patients with lvPPA, not all cases of lvPPA are attributed to AD pathology. […] TSPO-targeting tracers have been explored in PPA, with the goal of characterizing the role of microglial activation and associated neuroinflammation in the pathogenesis of PPA.

• #17 Primary Progressive Aphasia Causes and Diagnoses | Northwestern Medicine

  https://www.nm.org/conditions-and-care-areas/neurosciences/primary-progressive-aphasia/causes-and-diagnoses

  PPA arises when nerve cells in language-related parts of the brain malfunction. The underlying diseases are called degenerative because they cause gradually progressive nerve cell death that cannot be attributed to other causes such as head trauma, infection, stroke or cancer. There are several types of neurodegeneration that can cause PPA. […] PPA is caused by AD in approximately 30-40 percent of cases and by FTLD in approximately 60-70 percent of cases. In contrast, PPA is a very rare manifestation of AD. […] The logopenic type of PPA has a particularly high probability of being caused by AD. […] Sometimes these abnormalities become concentrated in language areas (instead of memory areas) of the brain and become the cause of PPA. […] So, while PPA patients dont have Alzheimers dementia, 30-40 percent may have an atypical form of Alzheimers disease.

• #18

  https://www.brain.northwestern.edu/dementia/primary-progressive-aphasia/symptoms-causes.html

  In the vast majority of individuals, PPA is not genetic. However, in a small number of families, PPA can be caused by hereditary forms of FTLD. The most common gene implicated in these families is the progranulin gene (GRN). Other, less-common genes implicated in FTLD include the microtubule associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9ORF72).

• #19 Primary Progressive Aphasia Causes and Diagnoses | Northwestern Medicine

  https://www.nm.org/conditions-and-care-areas/neurosciences/primary-progressive-aphasia/causes-and-diagnoses

  In the vast majority of individuals, PPA is not genetic. However, in a small number of families, PPA can be caused by hereditary forms of FTLD. […] Because PPA is progressive, decline in language ability continues. Additionally, some non-language abilities (memory, attention, judgment or changes in behavior and personality) can be affected. […] The rate of decline is variable from person to person and unfolds over many years. It is unclear why some people progress more rapidly than others.

• #20

  https://link.springer.com/article/10.1007/s00415-023-12030-4

  The responsible pathogenic mutation usually resides in one of the three major genes causing frontotemporal dementia: progranulin (GRN) (the most frequent genetic cause), chromosome 9 opening reading frame 72 (C9orf72) or (rarely) microtubule-associated protein tau (MAPT). […] We would argue, however, that clinicians have a stake in this enterprise on account of the very complexity of PPA and the difficulties that surround diagnosis and neuropathological correlation. […] There are several motivations to move beyond traditional neurolinguistic accounts of these syndromes to address core pathophysiological mechanisms of PPA. […] The neural networks implicated in the major PPA syndromes have been delineated in some detail, and network changes in these syndromes extend widely beyond the hubs of maximal atrophy seen on clinical brain MRI scans.

• #21 Primary progressive aphasia – Wikipedia

  https://en.wikipedia.org/wiki/Primary_progressive_aphasia

  In neurology, primary progressive aphasia (PPA) is a type of neurological syndrome in which language capabilities slowly and progressively become impaired. […] However, unlike most other aphasias, PPA results from continuous deterioration in brain tissue, which leads to early symptoms being far less detrimental than later symptoms. […] Currently, the specific causes for PPA and other degenerative brain disease similar to PPA are viewed as idiopathic (unknown). […] These autopsies, as well as imaging techniques such as CT scans, MRI, EEG, single photon emission computed tomography, and positron emission tomography, have generally revealed abnormalities to be almost exclusively in the left hemisphere. […] The most convincing genetic basis of PPA has been found to be a mutation in the GRN gene.

• #22 Primary Progressive Aphasia (PPA) – PsychDB

  https://www.psychdb.com/geri/dementia/primary-progressive-aphasia-ppa

  The vast majority of PPA cases are sporadic. Of the genes that have been identified, there is variability in transmission of these genes. Risk factor genes include GRN (granulin), MAPT (tau), C9ORF72 (protein C9orf72), and PSEN1 (presenilin1). […] Since PPA is a syndromic diagnosis, its’ pathophysiological etiology can be divided into one of two underlying pathophysiological processes: Alzheimer’s pathology (40-45% of cases) and Frontotemporal dementia pathology (55-60% of cases) […] For each PPA subtype, the most common neuropathologies are: Semantic: FTD with TDP-43 type C (80-90% of cases), Logopenic: Alzheimer’s, Non-fluent (agrammatic): FTD with tau (60% of cases).

• #23 SSA – POMS: DI 23022.485 – Primary Progressive Aphasia – 09/06/2022

  https://secure.ssa.gov/apps10/poms.nsf/lnx/0423022485

  Primary Progressive Aphasia (PPA) is a rare type of dementia characterized by slow and gradual loss of language (aphasia). […] Recent studies have concluded that individuals with PPA have a specific combination of prion gene variants, although this is not the primary cause of the disorder. […] Symptoms of PPA begin gradually, usually before the age of 65 years, and worsen over time. Individuals with PPA may become mute and eventually lose the ability to understand spoken or written language within 10 years of diagnosis. […] There is currently no effective treatment that can cure or slow the progression of PPA.

• #24

  https://link.springer.com/article/10.1007/s11910-021-01097-z

  Emerging evidence suggests that specific language network vulnerabilities caused by genetic, developmental, and/or lifestyle factors may determine why some people develop a PPA phenotype in the context of a specific proteinopathy. […] The motivation for moving beyond traditional neurolinguistics accounts of these syndromes to address core pathophysiological mechanisms is fourfold. […] Dynamic transformation of information (from percept to meaning and to action) is integral to the normal operation of the language system. […] Within this matrix, canonical PPA syndromes affect core neural processes relatively selectively.

• #25 Anatomy of Language Impairments in Primary Progressive Aphasia | Journal of Neuroscience

  https://www.jneurosci.org/content/31/9/3344

  Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by progressive decline in language function but relative sparing of other cognitive domains. […] Results showed regionally specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance. […] Poor fluency was associated with regions dorsal to the traditional boundaries of Broca’s area in the inferior frontal sulcus and the posterior middle frontal gyrus, whereas grammatical processing was associated with more widespread atrophy, including the inferior frontal gyrus and supramarginal gyrus. […] The correlation of atrophy with semantic processing impairment was localized to the anterior temporal poles. […] Atrophy patterns were more closely correlated with domain-specific performance than with subtype.

• #26

  https://link.springer.com/article/10.1007/s00415-023-12030-4

  Each of the canonical PPA phenotypes is predominantly associated with a particular neural network and underlying proteinopathy. […] This implies that the neural circuitry mediating the phenotype is preferentially vulnerable to that proteinopathy: a concept relevant to a broad range of neurodegenerative diseases, which we have termed molecular nexopathy. […] The speech and language deficits caused by proteinopathies need not closely resemble post-stroke aphasic syndromes. […] This speaks to the wider theme of pathophysiology, which we would argue underwrites all of the questions posed here and offers the best prospect of a transformative solution.

• #27 Primary progressive aphasia | Tidsskrift for Den norske legeforening

  https://tidsskriftet.no/en/2022/11/clinical-review/primary-progressive-aphasia

  New research techniques, such as those based on imaging methods that reflect the distribution of pathology in the brain, may well suggest alternative subdivisions. […] The purpose of this article is to provide a brief overview of the different variants of primary progressive aphasia. […] The core problem in the semantic variant of primary progressive aphasia is difficulty with word comprehension (semantics). […] The semantic variant is the best-defined variant in terms of signs and symptoms, imaging findings, and neuropathology. […] Brain magnetic resonance imaging (MRI) and positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) reveal atrophy and hypometabolism, respectively, in the anterior temporal lobes the temporal poles usually with a left-sided predominance. […] Characteristic MRI findings have good sensitivity (98 %) and specificity (93 %), and typical findings on FDG-PET are thought to have close to 100 % sensitivity and specificity.

• #28 Primary Progressive Aphasia: Toward a Pathophysiological Synthesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7861583/

  A candidate generic mechanism for svPPA is impaired computation of the featural statistics that support categorisation and identification of sensory stimuli, due to degradation of the neural activity patterns corresponding to coherent object and concept templates. […] The core mechanism of this syndrome may be impaired activation of phonemic templates, leading to deficient parsing of input sensory signals for transcoding to phonological output. […] A candidate, generic unifying mechanism may be impaired temporal scaffolding and/or combinatorial sequencing and scheduling of speech and other sensori-motor routines, particularly where these depend on predictive coding governed by learned rules.

• #29 Primary progressive aphasia | Tidsskrift for Den norske legeforening

  https://tidsskriftet.no/en/2022/11/clinical-review/primary-progressive-aphasia

  In the non-fluent/agrammatic variant of aphasia, the most common underlying pathology is frontotemporal lobar degeneration with tau inclusions, followed by amyloid pathology of the Alzheimer’s type and TDP-43 pathology. […] The non-fluent/agrammatic variant shows greater variation in terms of underlying pathology and further disease progression than the other variants. […] The logopenic variant is most often an aphasic variant of Alzheimer’s dementia, and patients eventually develop typical symptoms of Alzheimer’s disease. […] The pattern of dementia markers in cerebrospinal fluid varies depending on the underlying neuropathology.

• #30 Primary Progressive Aphasia | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/82030

  The pathophysiology of nfvPPA remains under investigation. This condition exhibits more pathology and disease progression variability than other PPA types. However, involvement of the dominant inferior frontal lobe (Broca area) is consistently observed, with atrophy of the insular cortex in the dominant hemisphere also common. This condition’s variability coincides with brain regions associated with language output, sentence processing, and motor speech programming. The pronounced variability of nfvPPA compared to other variants persists histologically and remains a subject of investigation. Many patients exhibit abnormal tau deposition upon postmortem examination, while a minority may show signs of TDP-43 or Alzheimer pathology. […] Meanwhile, lvPPA is most commonly an aphasic Alzheimer disease variant. Patients most frequently develop the typical clinical Alzheimer disease features. The pathology is similar to Alzheimer disease but with more left-sided perisylvian or parietal atrophy. Similar to Alzheimer disease, lvPPA also has amyloid and hyperphosphorylated tau accumulation.

• #31 FDG-PET in the Diagnosis of Primary Progressive Aphasia | Journal of Nuclear Medicine

  https://jnm.snmjournals.org/content/63/supplement_2/2971

  Previous studies have revealed alterations in regional glucose uptake in PPA patients. The three PPA subtypes show distinct patterns in FDG-PET imaging. […] Hypometabolism in the left thalamus and left inferior temporal gyrus, and the fusiform gyrus were reported in SD subtype. […] PNFA showed hypometabolism bilaterally in caudate nuclei, left hemisphere, thalamus, middle and superior temporal gyri, insula/inferior frontal gyrus, pars opercularis, lateral orbital gyrus, and middle frontal gyrus. […] LPA subtype showed hypometabolism in lateral temporoparietal and medial parietal lobes and left frontal lobe that differ from classical AD due to distinct atrophy patterns. […] These findings are complemented by concurrent findings of severe hypometabolism in the left temporal areas. […] Neuroimaging studies of patients with PPA showed a promising role of FDG-PET scan as a diagnostic modality especially in differentiating the subtypes of PPA. […] The value of FDG-PET in the diagnosis of PPA is especially underscored given the challenge of accurate diagnosis and prediction of future development of frontotemporal dementia (FTD).

• #32 Multimodality Imaging in Primary Progressive Aphasia | American Journal of Neuroradiology

  http://www.ajnr.org/content/43/9/1230

  Histopathologic studies have demonstrated asymmetric distribution of activated microglia in PPA, including high microglial densities in the superior temporal and inferior frontal gyri of the language-dominant hemisphere, consistent with postmortem and/or in vivo atrophy distribution. […] Patterns of microglial activation revealed variation favoring areas of increased atrophy in regions associated with language function, demonstrating concordance among patterns of microglial activation, atrophy, and clinical PPA phenotype.

• #33

  https://link.springer.com/article/10.1007/s00415-023-12030-4

  Here, we review recent progress in the diagnosis and management of primary progressive aphasia—the language-led dementias. […] We propose that pathophysiological mechanisms linking proteinopathies to phenotypes may help resolve the clinical complexity of primary progressive aphasia, and may suggest novel diagnostic tools and markers and guide the deployment of effective therapies. […] A nuanced version of the lumper perspective has recently gained ascendancy in the nosology of PPA. […] The application of multidimensional methods such as principal component analysis to neuropsychological datasets derived from large PPA cohorts has highlighted the extent to which the canonical syndromes overlap and the graded nature of deficits within as well as between diagnostic groups. […] This approach emphasises trans-syndromic factors that map onto particular cognitive factors (e.g. motor speech, phonological and semantic) over the canonical syndromes enshrined in the Gorno-Tempini criteria.

• #34 Meet the pioneers of primary progressive aphasia research – Northwestern Now

  https://news.northwestern.edu/stories/2022/04/primary-progressive-aphasia-research/

  Decades before the world learned about Bruce Willis aphasia diagnosis, Dr. Marsel Mesulam was pioneering a new field of research on a similar neurological condition: primary progressive aphasia (PPA), a rare, overlooked and underserved syndrome that destroys a persons language. […] What was causing this language disruption, he wondered? […] PPA also is known as Mesulams disease. […] PPA is difficult to diagnose. It requires expert consultation and a team approach to identify, said Sandra Weintraub, a professor of psychiatry and behavioral sciences and neurology at Feinberg and a member of the Mesulam Center. […] The observational research program has helped to define the syndrome and has allowed for the discovery of key insights related to diseases that cause PPA, including risk factors such as dyslexia.

• #35 FDG-PET in the Diagnosis of Primary Progressive Aphasia | Journal of Nuclear Medicine

  https://jnm.snmjournals.org/content/63/supplement_2/2971

  Primary progressive aphasia (PPA) is a disease that is known to affect the frontal and temporal regions of the left hemisphere. […] Although neuroimaging studies are needed to exclude other causes of aphasia such as stroke or tumor, they allow determination of the best approach for predicting pathology and diagnosis of the logopenic variant. […] Imaging criteria for PPA subtypes include changes in structure, metabolism, or perfusion in typical regions. […] Meta-analyses have shown disjunction between hypometabolism and atrophy in imaging studies on PPA, indicating the need for different diagnostic imaging criteria for 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) and for magnetic resonance imaging (MRI). […] FDG-PET enables visualization of metabolic alteration preceding atrophy. As such, FDG-PET has been applied extensively to PPA to assess underlying metabolic dysfunction.

• #36 Primary progressive aphasia: From syndrome to disease | Neurología (English Edition)

  https://www.elsevier.es/en-revista-neurologia-english-edition–495-articulo-primary-progressive-aphasia-from-syndrome-S2173580813000898

  Biomarkers in the CSF have been widely studied in Alzheimer disease, both for confirming the diagnosis and for identifying higher-risk patients during prodromal phases. These biomarkers may also be used for diagnosing atypical forms of AD onset, including progressive aphasia. […] Treatment is based on 3 fundamental pillars: symptomatic drug treatment and/or disease-modifying drugs; language rehabilitation and strategies for improving communication; and support for patients and caregivers.

• #37 The course of primary progressive aphasia diagnosis: a cross-sectional study | Alzheimer’s Research & Therapy | Full Text

  https://alzres.biomedcentral.com/articles/10.1186/s13195-022-01007-6

  Logopenic variant of PPA (lv-PPA) is a neurodegenerative syndrome frequently associated with biomarkers of AD. Lv-PPA patients display characteristic linguistic deficits, a pattern of brain atrophy, and possibly genetic susceptibility, which warrant considering this variant as a discrete AD endophenotype. […] Understanding in vivo pathological prediction is crucial in neurodegenerative diseases because therapeutic pharmacological strategies are, or soon will be, directed towards decreasing or clearing toxic molecules, such as amyloid, tau or TDP. This study highlights importance to improve early diagnosis of PPA to better understand links with AD. […] In summary, the comparison of clinical characteristics between PPA and AD patients could provide a better understanding of the reasons for network susceptibility generating clinical disorders increased on the language or memory.

• #38 Brain Sciences | Special Issue : Advances in Primary Progressive Aphasia

  https://www.mdpi.com/journal/brainsci/special_issues/Primary_Progressive_Aphasia

  Primary progressive aphasia is a clinical syndrome that includes a group of neurodegenerative disorders characterized by progressive language impairment. […] Notably, correlations between clinical findings and pathology have improved, and main clinical, neuroimaging, and genetic features have been described. […] Furthermore, primary progressive aphasia is a good model for the study of brain–behavior relationships, and has contributed to the knowledge of the neural basis of language functioning. […] However, there are many open questions remaining. […] For instance, classification into three variants (non-fluent, semantic, and logopenic) is under debate; further data about epidemiology and natural history of the diseases are needed; and, as in other neurodegenerative disorders, successful therapies are lacking.

• #39 Primary Progressive Aphasia – MD Searchlight

  https://mdsearchlight.com/neurology/primary-progressive-aphasia/

  The Semantic PPA variant is almost always associated with pathological aggregates found in most cases, called TDP-43-C. […] The Logopenic PPA variant is most often caused by Alzheimers disease pathology in around 95% of cases. […] Understanding the brains areas affected by PPA is key in diagnosing the disorder, estimating the patients prognosis, and developing therapies tailored to the patients unique language issues and affected brain areas. […] Different types of PPA will present different findings on imaging studies like brain MRI and FDG-PET scans. […] Currently, no medicines have been found to be effective for Primary Progressive Aphasia (PPA), a neurological syndrome that affects language capabilities. […] Its proven that speech and language therapy is the most successful way to manage PPA, particularly for motor speech issues. […] Transcranial direct current stimulation, a treatment that uses a simple electric current to stimulate specific areas of the brain, is viewed as a hopeful strategy to improve the results of language therapy in PPA patients.

• #40 Primary progressive aphasia: From syndrome to disease | Neurología (English Edition)

  https://www.elsevier.es/en-revista-neurologia-english-edition–495-articulo-primary-progressive-aphasia-from-syndrome-S2173580813000898

  Primary progressive aphasia (PPA) is a clinical syndrome characterised by a progressive decline in language and speech of neurodegenerative origin. Major breakthroughs made in recent years have lent us a better understanding of this syndrome, which may be the first manifestation of any of a number of neurodegenerative diseases. […] We reviewed the main aspects of PPA epidemiology, clinical manifestations, diagnosis, aetiology and treatment. Most cases manifest sporadically and the typical age of onset is between 50 and 70 years. Three clinically distinct variants have been described: nonfluent or agrammatic PPA, semantic PPA and logopenic PPA. Each of these variants tends to be associated with specific histopathological findings, but clinical diagnostic methods are imperfect predictors of underlying pathology. Anatomical and functional neuroimaging can provide useful biomarkers. Several treatments have been proposed, and while no clear benefits have been demonstrated, acetylcholinesterase inhibitors may be useful, especially in the logopenic variant.

• #41 Six things to know about primary progressive aphasia

  https://www.ualberta.ca/en/folio/2024/06/six-things-to-know-about-primary-progressive-aphasia.html

  The conditions correct name is frontotemporal degeneration. Its one of the underlying disease processes that can cause primary progressive aphasia (PPA), says Esther Kim, a speech-language pathologist, chair of the Department of Communication Sciences and Disorders in the University of Albertas Faculty of Rehabilitation Medicine and member of the Neuroscience and Mental Health Institute. […] Primary progressive aphasia is a rare syndrome affecting one in 100,000 people, says Kim, referring to a 2022 study. It can be caused by several underlying disease processes, including frontotemporal degeneration, Lewy body disease or Alzheimers disease. […] Those processes cause atrophy (shrinking) of brain tissue in the lobes behind the forehead and behind the ears, mainly in the brains left hemisphere areas important for processing language. […] If the PPAs underlying disease process is Alzheimers, drugs for that disease may be used. But treatment usually concentrates on maintaining communication and quality-of-life functioning through psychological support and speech-language therapy.

• #42 Primary Progressive Aphasia: Here’s What You Need to Know

  https://www.flintrehab.com/primary-progressive-aphasia/?srsltid=AfmBOop0MIIKhn9rFkbJ1vqm44GQFmi_l8F9lQvw8-AUiG6Llsg9DHv_

  Primary progressive aphasia often stems from frontotemporal lobe dementia. This type of dementia is characterized by focal syndromes, such as progressive language deterioration or behavioral changes. […] Individuals with frontotemporal dementia experience a deterioration of nerve cells in the frontal and/or temporal lobes of the brain. […] Of note, the logopenic variant is typically caused by Alzheimer pathology, while the other two variants usually result from frontotemporal dementias. […] Speech therapy is sometimes able to slow the progression of the disease. […] Speech therapy exercises work by activating neuroplasticity. […] These pathways can allow undamaged portions of the brain to take control of functions that were previously controlled by damaged areas. […] Therefore, even if progressive aphasia damages the brain regions that normally control language production, it may still be possible for other areas to compensate.

• #43 Meet the pioneers of primary progressive aphasia research – Northwestern Now

  https://news.northwestern.edu/stories/2022/04/primary-progressive-aphasia-research/

  There are at least six diseases that cause PPA, including atypical forms of Alzheimers disease, frontotemporal degeneration with tauopathy, Picks disease and three different forms of frontotemporal degeneration with TDP-43 abnormality, Mesulam said. Each one at present is incurable. So, the first goal is not only to diagnose the exact underlying diseases but also to be able to treat them. […] His second goal is to study those with PPA even more deeply and to learn more about language in the human brain, which is the only unique function of the human brain and what makes our brain human, Mesulam said.

• #44

  https://link.springer.com/article/10.1007/s00415-023-12030-4

  Predicting the underlying proteinopathy in PPA is potentially relevant to prognosis and care planning, and will be increasingly required for the rational targeting of disease-modifying therapies. […] The strongest and most consistent association links svPPA to TAR-DBA-binding-protein (TDP)-43 type C pathology, in line with the striking clinico-anatomical coherence of this syndrome. […] lvPPA is widely regarded as a predictor of Alzheimer pathology and this association provides a neuropathological substrate for its extensive phenotypic overlap with typical amnestic and visual variant Alzheimer syndromes. […] However, the strength of the association varies between series. […] Most cases of PPA are sporadic; however, a significant minority are genetically mediated, with autosomal dominant inheritance.

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