Abstract
This systematic review describes primary progressive aphasia (PPA) variants and includes the authors' own clinical observations. Over 20 genes have now been identified, with mutations that are directly involved in the development of the behavioural variant of frontotemporal dementia, as well as other forms of PPA. Pathomorphological markers of Alzheimer's disease were identified in 76% of cases of logopenic PPA, while signs of frontotemporal dementia associated with TDP-43 were identified in 80% of cases of the semantic variant, and those associated with TDP-43/tau were identified in 64% of cases of agrammatic PPA. The clinical diagnosis of PPA is based on a history of long-term, progressive speech disturbances and identifying a particular variant: agrammatic, semantic or logopenic. The primary variant of the speech disorder cannot be identified in approximately 30% of cases. The focus should be on the main and additional clinical signs (presence of agrammatism, object naming, word comprehension, preserved repetition), as well as neuroimaging (presence of asymmetrical frontal and/or temporal lobe atrophy).
 The article also provides key aspects of differential diagnosis of the PPA variants, and puts forth a stepwise diagnostic algorithm. It examines features of PPA progression, with possible development of corticobasal syndrome, illustrated by a clinical case. A dissociation between neuroimaging findings and clinical disease variant is also demonstrated to be possible. Different neuropsychological assessments of patients with aphasia and methods of determining the severity of speech dysfunction are presented. Standardized aphasia assessment tools and the adapted PPA severity scale are provided.
Highlights
This systematic review describes primary progressive aphasia (PPA) variants and includes the authors' own clinical observations
Over 20 genes have been identified, with mutations that are directly involved in the development of the behavioural variant of frontotemporal dementia, as well as other forms of PPA
Pathomorphological markers of Alzheimer's disease were identified in 76% of cases of logopenic PPA, while signs of frontotemporal dementia associated with TDP-43 were identified in 80% of cases of the semantic variant, and those associated with TDP-43/tau were identified in 64% of cases of agrammatic PPA
Summary
The article provides key aspects of differential diagnosis of the PPA variants, and puts forth a stepwise diagnostic algorithm. Аграмматический (аППА) и семантический (сППА) варианты ППА в большинстве случаев входят в группу лобновисочных дегенераций (ЛВД), тогда как логопенический вариант (лППА) чаще всего представляет собой атипичную форму болезни Альцгеймера. В настоящее время идентифицированы более 20 генов, мутации в которых непосредственно участвуют в развитии как поведенческой формы ЛВД, так и других форм ППА. Большинство семейных случаев ЛВД (более 75%) ассоциированы с мутациями 3 генов: GRN (кодирует белок програнулин), MAPT (кодирует микротубулярный тау-белок) и C9orf (кодирует одноименный белок) [6, 7]. Мутации в гене GRN (Granulin precursor, предшественник програнулина) являются второй по частоте мутацией при ЛВД и приводят к развитию 5–25% семейных случаев заболевания [13]. Патогенные мутации в гене MAPT (Microtubule Associated Protein Tau) составляют около 5–20% семейных случаев ЛВД [16]. Мутации в гене MAPT могут приводить к нарушению способности таубелка связываться с микротрубочками, а также повышать его фибрилизационную активность, в результате чего агрегаты нейрофиламентов накапливаются в нейронах и глиальных клетках коры, белого вещества, подкорковых структур и ядер ствола, а также спинного мозга [17]
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