Primary progressive aphasia presents with aphasia, with or without other minor cognitive dysfunction. It refers to core linguistic disorders caused by neurodegenerative disease. Three main PPA variants are recognized:...Primary progressive aphasia presents with aphasia, with or without other minor cognitive dysfunction. It refers to core linguistic disorders caused by neurodegenerative disease. Three main PPA variants are recognized: nonfluent/agrammatic, semantic and logopenic. Correctly classifying patients during life according to the underlying histopathology will become increasingly important as cause-specific treatments become available. This article reviews clinical and histopathological studies of PPA, with particular reference to updated PPA classifications. Currently, one-to-one relationships do not exist within PPA subtypes. The semantic variant has the best correspondence between the clinical syndrome and the underlying pathological cause and the logopenic variant the worst correspondence. The use of future biomarkers should facilitate accurate clinicopathological correlation of patients during life.展开更多
Background Primary progressive aphasia(PPA)is a neurodegenerative disorder characterized by a gradual,insidious and progressive loss of language abilities,with naming difficulties being an early and persistent impairm...Background Primary progressive aphasia(PPA)is a neurodegenerative disorder characterized by a gradual,insidious and progressive loss of language abilities,with naming difficulties being an early and persistent impairment common to all three variants.In the absence of effective pharmacological treatments and given the progressive nature of the disorder,in the past few decades,many studies have investigated the effectiveness of language training to minimize the functional impact of word-finding difficulties in daily life.Main body We review language treatments most commonly used in clinical practice among patients with different variants of PPA,with a focus on the enhancement of spoken and written naming abilities.Generalization of gains to the ability to name untrained stimuli or to other language abilities and the maintenance of these results over time are also discussed.Forty-eight studies were included in this literature review,identifying four main types of language treatment:a)lexical retrieval treatment,b)phonological and/or orthographic treatment,c)semantic treatment,and d)a multimodality approach treatment.Overall,language training is able to induce immediate improvements of naming abilities in all variants of PPA.Moreover,despite the large variability among results,generalization and long-term effects can be recorded after the training.The reviewed studies also suggest that one factor that determines the choice of a particular approach is the compromised components of the lexical/semantic processing system.Conclusion The majority of studies have demonstrated improvements of naming abilities following language treatments.Given the progressive nature of PPA,it is essential to apply language treatment in the early stages of the disease.展开更多
Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal lobes.Frontotemporal lobar degeneration is consider...Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal lobes.Frontotemporal lobar degeneration is considered to be equivalent to frontotemporal dementia.Frontotemporal dementia is characterized by progressive impairments in behavior,executive function,and language.There are two main clinical subtypes:behavioral-variant frontotemporal dementia and primary progressive aphasia.The early diagnosis of frontotemporal dementia is critical for developing management strategies and interventions for these patients.Without validated biomarkers,the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features,but misdiagnosis often occurs due to overlap with a range of neurologic and psychiatric disorders.In the studies reviewed a very large number of microRNAs were found to be dysregulated but with limited overlap between individual studies.Measurement of specific miRNAs singly or in combination,or as miRNA pairs(as a ratio)in blood plasma,serum,or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls,Alzheimer’s disease,and amyotrophic lateral sclerosis.Furthermore,upregulation of miR-223-3p and downregulation of miR-15a-5p,which occurred both in blood serum and cerebrospinal fluid,distinguished behavioral-variant frontotemporal dementia from healthy controls.Downregulation of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia,respectively,from healthy controls.Possible strong miRNA biofluid biomarker contenders for behavioral-variant frontotemporal dementia are miR-223-3p,miR-15a-5p,miR-22-3p in blood serum and cerebrospinal fluid,and miR-124 in cerebrospinal fluid.No miRNAs were identified able to distinguish between behavioral-variant frontotemporal dementia and primary progressive aphasia subtypes.Further studies are warranted on investigating miRNA expression in biofluids and frontal/temporal cortical tissue to validate and extend these findings.展开更多
文摘Primary progressive aphasia presents with aphasia, with or without other minor cognitive dysfunction. It refers to core linguistic disorders caused by neurodegenerative disease. Three main PPA variants are recognized: nonfluent/agrammatic, semantic and logopenic. Correctly classifying patients during life according to the underlying histopathology will become increasingly important as cause-specific treatments become available. This article reviews clinical and histopathological studies of PPA, with particular reference to updated PPA classifications. Currently, one-to-one relationships do not exist within PPA subtypes. The semantic variant has the best correspondence between the clinical syndrome and the underlying pathological cause and the logopenic variant the worst correspondence. The use of future biomarkers should facilitate accurate clinicopathological correlation of patients during life.
基金This work was supported by the Italian Ministry of Health(Ricerca Corrente and Giovani Ricercatori grant GR-2018-12365105).
文摘Background Primary progressive aphasia(PPA)is a neurodegenerative disorder characterized by a gradual,insidious and progressive loss of language abilities,with naming difficulties being an early and persistent impairment common to all three variants.In the absence of effective pharmacological treatments and given the progressive nature of the disorder,in the past few decades,many studies have investigated the effectiveness of language training to minimize the functional impact of word-finding difficulties in daily life.Main body We review language treatments most commonly used in clinical practice among patients with different variants of PPA,with a focus on the enhancement of spoken and written naming abilities.Generalization of gains to the ability to name untrained stimuli or to other language abilities and the maintenance of these results over time are also discussed.Forty-eight studies were included in this literature review,identifying four main types of language treatment:a)lexical retrieval treatment,b)phonological and/or orthographic treatment,c)semantic treatment,and d)a multimodality approach treatment.Overall,language training is able to induce immediate improvements of naming abilities in all variants of PPA.Moreover,despite the large variability among results,generalization and long-term effects can be recorded after the training.The reviewed studies also suggest that one factor that determines the choice of a particular approach is the compromised components of the lexical/semantic processing system.Conclusion The majority of studies have demonstrated improvements of naming abilities following language treatments.Given the progressive nature of PPA,it is essential to apply language treatment in the early stages of the disease.
文摘Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal lobes.Frontotemporal lobar degeneration is considered to be equivalent to frontotemporal dementia.Frontotemporal dementia is characterized by progressive impairments in behavior,executive function,and language.There are two main clinical subtypes:behavioral-variant frontotemporal dementia and primary progressive aphasia.The early diagnosis of frontotemporal dementia is critical for developing management strategies and interventions for these patients.Without validated biomarkers,the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features,but misdiagnosis often occurs due to overlap with a range of neurologic and psychiatric disorders.In the studies reviewed a very large number of microRNAs were found to be dysregulated but with limited overlap between individual studies.Measurement of specific miRNAs singly or in combination,or as miRNA pairs(as a ratio)in blood plasma,serum,or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls,Alzheimer’s disease,and amyotrophic lateral sclerosis.Furthermore,upregulation of miR-223-3p and downregulation of miR-15a-5p,which occurred both in blood serum and cerebrospinal fluid,distinguished behavioral-variant frontotemporal dementia from healthy controls.Downregulation of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia,respectively,from healthy controls.Possible strong miRNA biofluid biomarker contenders for behavioral-variant frontotemporal dementia are miR-223-3p,miR-15a-5p,miR-22-3p in blood serum and cerebrospinal fluid,and miR-124 in cerebrospinal fluid.No miRNAs were identified able to distinguish between behavioral-variant frontotemporal dementia and primary progressive aphasia subtypes.Further studies are warranted on investigating miRNA expression in biofluids and frontal/temporal cortical tissue to validate and extend these findings.
