Primary progressive aphasia (PAP) is a slowly increasing but progressively progressive disorder that leads to loss of speech function. It was allocated as 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 onset is 50 years, but there are known cases of primary progressive aphasia in patients from 20 to 82 years old. It takes about 7 years from the initial clinical manifestations to the complete collapse of speech.

Currently, several etiofactors are known that lead to the manifestation of primary progressive aphasia. The studied causes correlate with different forms of PPA. Among them:

1. Taupathies . Neurodegenerative pathologies caused by the deposition of tau protein in neurons and neuroglia include frontotemporal degeneration, corticobasal degeneration , and progressive supranuclear palsy . The development of the agrammatic form of PPA is associated with this etiological factor.
2. TDP -43-patio. These include diseases caused by the intracellular accumulation of the TDP-43 protein: lobar 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.
3. β – amyloidopathy. The combination of β-amyloid and tau protein deposition is pathognomonic for logopenic PPA in atypical Alzheimer’s disease.
4. Heredity . Cases of primary progressive aphasia as a hereditary pathology with autosomal dominant transmission have been described. The mutation was detected in the GRN gene, which encodes the expression of the granulin protein on chromosome 17. Hereditary PAD is referred to as familial frontotemporal dementia .

The syndrome of primary progressive aphasia is pathomorphologically heterogeneous. The DNA-binding protein TDP-43 is responsible for DNA transcription in neurons in the cerebral cortex. Its excessive accumulation in the nuclei of neurons and the impossibility of excretion 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 neuronal development, the formation of microtubules in nerve cells. However, hyperphosphorylated tau protein forms neurofibrillary glomeruli that disrupt the functioning of nerve tissue.

Primary pathological changes in agrammatic progressive aphasia are found in the superior and middle frontal gyri, insular lobe. With the logopenic form of PPA, local atrophic changes are observed mainly in the posterior parts of the frontal and parietal lobes, with the semantic form – in the temporal cortex of the dominant hemisphere.

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 disorder, features of pathomorphology and neuroimaging:

1. Agrammatic . The leading defect is oral dyspraxia combined with grammatical disorders.
2. Semantic . The central mechanism is the disorder of understanding the meaning of the statement.
3. Logopenic . The main criteria are the difficulty of pronouncing and repeating words.
4. Combined . Combines the agrammatic and semantic form of the PPA.

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 any neurological symptoms. Subsequently, the language deficit grows rapidly and remains the leading one in the structure of the syndrome, a decrease in intelligence appears, a change in behavior, etc.

Agrammatic PPA

In the debut of this form of primary progressive aphasia, non-convulsive hesitation , stuttering , and pauses in speech occur . Speech activity gradually decreases. The patient begins to express himself in the “telegraphic style“, a foreign accent may appear in his speech . The understanding of the meaning of words and syntactic constructions is preserved.

There are literal paraphasias , perseverations, and grammatisms in oral speech and writing. Further reading and writing becomes impossible ( alexia , agraphia). In the presence of oral apraxia, repeated speech suffers. Anomie arises. In an advanced stage, mutism develops.

In the neurological status – muscle rigidity, hypokinesia, tremor . Behavioral deviations join later: apato-abulic syndrome, depression, obsessive states.

Semantic PPA

It starts at the age of 50-60. Clinical signs include a reduction in vocabulary, alienation of the meaning of a word, and 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. Counting is saved, writing and reading are partially impaired ( dysgraphia , dyslexia ), but reading / writing comprehension suffers.

Typical visual (including facial) agnosia , possibly the development of parkinsonism . The behavior of patients with semantic primary progressive aphasia is characterized by a loss of empathy, excessive pedantry, stinginess, obsessive-compulsive actions.

Logopenic PPA

Initially, patients have difficulty finding the word they need, both when naming objects and in spontaneous speech. Because of this, speech becomes slower. Repetition of sentences is difficult. Phonetic errors are noted. There are no agrammatisms, understanding is not broken. Logopenic form of progressive aphasia often precedes the extensive clinic of Alzheimer’s disease.

Complications are associated with the progression of causal neurodegenerative pathology and language deficits. After the initial two-year period, speech difficulties, cognitive and behavioral abnormalities begin to grow like an avalanche. Patients gradually lose the ability to communicate, self-service, become dependent on the help of loved ones. In the outcome of primary progressive aphasia, profound dementia and total aphasia inevitably develop .

The correct diagnosis is rarely made in patients with progressive primary aphasia. Most cases are usually mistakenly classified as discirculatory encephalopathy. This is facilitated by the fact that the complaints of patients visiting a neurologist are nonspecific in the initial stages: forgetfulness of words and faces, difficulties in understanding. Confirm the PPA is helped by:

• MRI of the brain . It is informative in the expanded stage, when areas of local atrophy of various areas of the brain are determined on tomograms (depending on the form of PPA). Helps to exclude damage to cerebral vessels, cerebral infarctions, tumors and other causes of aphasia.
• PET-CT of the brain . Positron emission tomography with fluorodeoxyglucose detects local zones of glucose hypometabolism, which confirms degenerative changes in the nervous tissue. PET-CT with [11C] PIB is used to detect amyloid plaques, their localization and density.
• EFI methods. EEG and registration of evoked cognitive potentials are performed . Electroencephalography with functional tests demonstrates oppression and irregularity of the cortical rhythm. The P300 study indicates cognitive deficits of varying severity.
• Neuropsychological tests . The study of HMF can show different results, taking into account the stage of primary progressive aphasia. In all forms and in any period, speech difficulties are revealed. Violation of praxis and gnosis is possible. Memory and thinking suffer in later stages.

Methods of genetic diagnostics have been developed for some forms of PPA . Primary progressive aphasia is differentiated from 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.

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 state and maintenance of the quality of life. With a symptomatic purpose, the following are prescribed:

• NMDA antagonists. Against the background of the use of memantine in patients with primary progressive aphasia, there is a moderate improvement in cognitive functions.
• Dopaminomimetics. Levodopa, bromocriptine is used both to eliminate the symptoms of parkinsonism and to overcome articulatory dyspraxia.
• Cholinesterase inhibitors. Drugs in this group reduce the severity of cognitive deficits, help control behavioral disorders, and slow the progression of dementia.
• SSRIs. They are prescribed for the development of behavioral and affective disorders.
• Other drugs. A certain effect is provided by long-term use of nootropic drugs. Vitamin D deficiency is being corrected.

Logotherapy

Patients with PPA are shown systematic sessions with a speech therapist-aphasiologist , a psychologist. In the process of logotherapy , an improvement in speech perception is achieved, a decrease in articulatory difficulties, although in general these positive changes are insignificant and are temporary in nature. To compensate for language difficulties, special mobile applications, PECS cards, can be used.