Primary progressive aphasia is a gradual breakdown of speech function in the absence of cognitive disorders. It debuts with speech stutters, agrammatism, paraphasias, speech retardation, which gradually transform into gross motor or global aphasia. Progressive aphasia is diagnosed according to EEG data, evoked potentials studies, brain tomography (MRI, PET-CT), neuropsychological testing. Symptomatic pharmacotherapy (nootropics, NMDA antagonists, acetylcholinesterase inhibitors, SSRIs), speech therapy classes are used in the treatment.
General information
Primary progressive aphasia (PPA) is a slowly increasing but continuously progressive disorder that leads to loss of speech functions. It was isolated into an independent nosology in 1982, although it was first described more than a century ago. In modern neurology, PPA is included in the group of focal neurodegenerative processes and occupies 20-40% in their structure. The average age of the debut is 50 years, but there are cases of primary progressive aphasia in patients from 20 to 82 years old. From the initial clinical manifestations to the complete disintegration of speech, about 7 years pass.
Causes
At the moment, several etiofactors are known that lead to the manifestation of primary progressive aphasia. The studied causes correlate with different forms of PPA. Among them:
- Taupathy. Neurodegenerative pathologies caused by deposition of tau protein in neurons and neuroglia include frontotemporal degeneration, corticobasal degeneration, progressive supranuclear paralysis. This etiological factor is associated with the development of the agrammatic form of PPA.
- TDP-43-patii. These include diseases caused by intracellular accumulation of the TDP-43 protein: lobular frontotemporal degeneration, motor neuron disease, dementia with Lewy bodies, etc. They are characteristic of the semantic, part of the agrammatic and logopenic forms of PPA.
- β-amyloidopathy. The combination of beta-amyloid deposition and tau protein is pathognomonic for the logopenic variant of PPA in the atypical variant of Alzheimer’s disease.
- Heredity. Cases of primary progressive aphasia as a hereditary pathology with autosomal dominant transmission are described. The mutation was detected in the GRN gene encoding the expression of the granulin protein on chromosome 17. Hereditary PPA is attributed to familial frontotemporal dementia.
Pathogenesis
The syndrome of primary progressive aphasia is pathomorphologically heterogeneous. DNA-binding protein TDP-43 is responsible for transcription of DNA in neurons of the cerebral cortex. Its excessive accumulation in the nuclei of neurons and the inability to be excreted into the cytoplasm triggers the process of neurodegeneration. Clinically, this is expressed in the development of frontotemporal atrophy.
Tau protein is an important neurobiochemical regulator of the development of neurons, the formation of microtubules in nerve cells. However, hyperphosphorylated tau protein forms neurofibrillary glomeruli that disrupt the functioning of nervous tissue.
Primary pathological changes in agrammatic progressive aphasia are found in the upper and middle frontal gyrus, insular lobe. In the logopenic form of PPA, local atrophic changes are observed mainly in the posterior parts of the frontal and parietal lobes, in the semantic – in the temporal cortex of the dominant hemisphere.
Classification
Taking into account the clinical variant of development, primary progressive aphasias are divided into 4 forms. They are based on the criteria of speech function disorders, features of pathomorphology and neuroimaging:
- Agrammatic. The leading defect is oral dyspraxia in combination with grammatical disorders.
- Semantic. The central mechanism is a disorder of understanding the meaning of the utterance.
- Logopenic. The main criteria are difficulties in pronouncing and repeating words.
- Combined. Combines the agrammatic and semantic form of the PPA.
Symptoms
For all forms of primary progressive aphasia, a slow, gradual (over several years) increase in speech disorders is typical. At the same time, at least in the first two years, patients have no cognitive decline and no neurological symptoms. Subsequently, the language deficit increases rapidly and remains the leading one in the structure of the syndrome, there is a decrease in intelligence, a change in behavior, etc.
Agrammatic PPA
In the debut of this form of primary progressive aphasia, non-convulsive stuttering, stuttering, pauses in speech occur. Speech activity gradually decreases. The patient begins to express himself in a “telegraphic style”, a foreign accent may appear in the speech. Understanding the meaning of words and syntactic constructions is preserved.
There are literal paraphasias, perseverations, agrammatism in oral speech and writing. Further reading and writing becomes impossible (Alexia, agraphy). In the presence of oral apraxia, repeated speech suffers. There is an anomie. In an advanced stage, mutism develops.
In the neurological status ‒ muscle rigidity, hypokinesia, tremor. Later, behavioral deviations are added: apathetic-abusive syndrome, depression, obsessive states.
Semantic PPA
It begins at the age of 50-60 years. Clinical signs include vocabulary reduction, alienation of the meaning of the word, verbal paraphasias. Patients can describe or draw an object, but find it difficult to call it a word, poorly understand the meaning of low-frequency words. The score is saved, writing and reading are partially impaired (dysgraphy, dyslexia), but the understanding of what is written/read suffers.
Typical visual (including facial) agnosia, possible development of Parkinsonism. The behavior of patients with semantic primary progressive aphasia is characterized by loss of empathy, excessive pedantry, avarice, obsessive-compulsive actions.
Logopenic PPA
Initially, patients have difficulty finding the right word, both when naming objects and in spontaneous speech. Because of this, speech becomes slow. Repetition of sentences causes difficulties. Phonetic errors are noted. There are no agrammatism, understanding is not broken. The logopenic form of progressive aphasia often precedes the expanded clinic of Alzheimer’s disease.
Complications
Complications are associated with the progression of causal neurodegenerative pathology and language deficiency. After the initial two-year period, speech difficulties, cognitive and behavioral deviations begin to increase avalanche-like. Patients gradually lose the ability to communicate, self-care, become dependent on the help of loved ones. In the outcome of primary progressive aphasia, deep dementia and total aphasia inevitably develop.
Diagnostics
The correct diagnosis of patients with primary progressive aphasia is rarely made. Most cases are usually mistakenly classified as dyscirculatory encephalopathy. This is facilitated by the fact that the complaints of patients who consult a neurologist are non-specific in the initial stages: forgetfulness of words and faces, difficulties of understanding. They help to confirm the PPA:
- MRI of the brain. It is informative in the expanded stage, when areas of local atrophy of various brain regions are determined on tomograms (depending on the form of PPA). It helps to exclude damage to cerebral vessels, brain infarctions, tumors and other causes of aphasia.
- PET-CT of the brain. Positron emission tomography with fluorodeoxyglucose detects local areas of glucose hypometabolism, which confirms degenerative changes in nervous tissue. PET-CT with [11C] PIB is used to detect amyloid plaques, their localization and density.
- EFI methods. An EEG is performed and the evoked cognitive potentials are recorded. Electroencephalography with functional tests demonstrates depression and irregularity of the cortical rhythm. The P300 study indicates cognitive deficits of varying severity.
- Neuropsychological tests. The VPF study may show different results taking into account the stage of primary progressive aphasia. In all forms and in any period, speech difficulties are revealed. Possible violation of praxis and gnosis. Memory and thinking suffer in later stages.
Methods of genetic diagnostics have been developed for some forms of PPA. Primary progressive aphasia is differentiated with speech disorders and dementia caused by cerebrovascular diseases, neuroinfections, encephalopathies (uremic, hepatic, etc.), tumor processes, neurological disorders with vitamin B12 deficiency, Neumann-Pick type C disease, etc.
Treatment
Drug therapy
To date, no effective therapy has been proposed that can stop or significantly slow down the progression of PPA. We are talking about the possible stabilization of the condition and maintaining the quality of life. For symptomatic purposes
- NMDA antagonists are prescribed. Against the background of the use of memantine in patients with primary progressive aphasia, there is a moderate improvement in cognitive functions.
- Dopaminomimetics. Levodopa and bromocriptine are used both to eliminate the symptoms of parkinsonism and to overcome articulatory dyspraxia.
- Cholinesterase inhibitors. Drugs of this group reduce the severity of cognitive deficits, help control behavioral disorders, slow down the progression of dementia.
- SSRIs. They are prescribed for the development of behavioral and affective disorders.
- Other drugs. A certain effect is given by long-term use of nootropic drugs. Correction of vitamin D deficiency is being carried out.
Logotherapy
Patients with PPA are shown systematic classes with a speech therapist-aphasiologist, psychologist. In the process of logotherapy, speech perception is improved, articulation difficulties are reduced, although in general these positive changes are insignificant and temporary. To compensate for language difficulties, special mobile applications, PECS cards can be used.
Prognosis and prevention
In general, the prognosis is characterized as unfavorable, since in all cases of primary progressive aphasia, an increase in aphasic disorders and dementia is recorded. The average life expectancy after diagnosis is 8-10 years.
Specific preventive measures have not been developed. As well as to prevent other types of dementia, it is recommended to eliminate possible risk factors (dyslipidemia, obesity), compensation for concomitant pathologies. Conducting active mental activity throughout life has a certain protective effect.