Primary progressive aphasia (PPA) is a type of neurological syndrome in which language capabilities slowly and progressively become impaired. As with other types of
aphasia
Aphasia is an inability to comprehend or formulate language because of damage to specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine but aphasia due to stroke is estimated to be 0.1–0.4% in th ...
, the symptoms that accompany PPA depend on what parts of the
left hemisphere
The lateralization of brain function is the tendency for some neural functions or cognitive processes to be specialized to one side of the brain or the other. The median longitudinal fissure separates the human brain into two distinct cerebra ...
are significantly damaged. 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. Those with PPA slowly lose the ability to speak, write, read, and generally comprehend language. Eventually, almost every patient becomes mute and completely loses the ability to understand both written and spoken language.
Although it was first described as solely impairment of language capabilities while other mental functions remain intact,
it is now recognized that many, if not most of those with PPA experience impairment of memory, short-term memory formation and loss of
executive functions
In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and succe ...
. It was first described as a distinct syndrome by M. Marsel Mesulam in 1982. Primary progressive aphasias have a clinical and pathological overlap with the
frontotemporal lobar degeneration
Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.
Commo ...
(FTLD) spectrum of disorders and
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. However, PPA is not considered synonymous to Alzheimer's disease due to the fact that, unlike those affected by Alzheimer's disease, those with PPA are generally able to maintain the ability to care for themselves, remain employed, and pursue interests and hobbies. Moreover, in diseases such as Alzheimer's disease,
Pick's disease
Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as ...
, and
Creutzfeldt-Jakob disease, progressive deterioration of comprehension and production of language is just one of the many possible types of mental deterioration, such as the progressive decline of memory, motor skills, reasoning, awareness, and visuospatial skills.
Causes
Currently, the specific causes for PPA and other degenerative brain disease similar to PPA are unknown. Autopsies have revealed a variety of brain abnormalities in people who had PPA. These autopsies, as well as imaging techniques such as CT scans, MRI, EEG,
single photon emission computed tomography
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
(SPECT), and
positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
(PET), have generally revealed abnormalities to be almost exclusively in the left hemisphere.
Risk factors
There have been no large epidemiological studies on the incidence and prevalence of the PPA variants. Though it most likely has been underestimated, onset of PPA has been found to occur in the sixth or seventh decade.
There are no known environmental risk factors for the progressive aphasias. However, one observational, retrospective study suggested that
vasectomy
Vasectomy, or vasoligation, is an elective surgical procedure for male sterilization or permanent contraception. During the procedure, the male vasa deferentia are cut and tied or sealed so as to prevent sperm from entering into the urethra and ...
could be a risk factor for PPA in men. These results have yet to be replicated or demonstrated by prospective studies.
PPA is not considered a hereditary disease. However, relatives of a person with any form of
frontotemporal lobar degeneration
Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.
Commo ...
, including PPA, are at slightly greater risk of developing PPA or another form of the condition. In a quarter of patients diagnosed with PPA, there is a family history of PPA or one of the other disorders in the FTLD spectrum of disorders. It has been found that genetic predisposition varies among the different PPA variants, with PNFA being more commonly familial in nature than LPA or SD.
The most convincing genetic basis of PPA has been found to be a mutation in the GRN gene. Most patients with observed GRN mutations present clinical features of PNFA, but the phenotype can be atypical.
Diagnosis
Diagnostic criteria
The following diagnosis criteria were defined by Mesulam:
* As opposed to having followed trauma to the brain, a patient must show an insidious onset and a gradual progression of aphasia, defined as a disorder of sentence and/or word usage, affecting the production and comprehension of speech.
* The disorder in question must be the only determinant on functional impairment in the activities of the patient's daily living.
* On the basis of diagnostic procedures, the disorder in question must be unequivocally attributed to a neurodegenerative process.
Whether or not PPA and other aphasias are the only source of cognitive impairment in a patient is often difficult to assess because: 1) as with other neurologically degenerative diseases, such as Alzheimer's disease, there are currently no reliable non-invasive diagnostic tests for aphasias, and thus neuropsychological assessments are the only tool physicians have for diagnosing patients; and 2) aphasias often affect other, non-language portions of these neuropsychological tests, such as those specific for memory.
Classification
In 2011, the classification of primary progressive aphasia was updated to include three clinical variants. Patients must first be diagnosed with PPA, and then divided into variants based on speech production features, repetition, single- word and syntax comprehension, confrontation naming, semantic knowledge, and reading/spelling.
In the classical Mesulam criteria for primary progressive aphasia, there are two variants: a non-fluent type
progressive nonfluent aphasia (PNFA) and a fluent type
semantic dementia
Semantic dementia (SD), also known as semantic variant primary progressive aphasia (svPPA), is a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains. However, the most common p ...
(SD).
A third variant of primary progressive aphasia,
logopenic progressive aphasia
Logopenic progressive aphasia (LPA) is a variant of primary progressive aphasia. It is defined clinically by impairments in naming and sentence repetition. It is similar to conduction aphasia and is associated with atrophy to the left posterior te ...
(LPA) was then added, and is an atypical form of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. For PNFA, The core criteria for diagnosis includes agrammatism and slow, and labored speech. Inconsistent speech sound errors are also very common, including distortions, deletions, and insertions. In terms of comprehension, there are deficits in syntax and sentence comprehension due to grammatical complexity, but single- word and object comprehension is relatively maintained.
The second variant, SD, presents with deficits in single-word and object comprehension. Naming impairments can be severe, specially for low-frequency objects, and can eventually lead to a more widespread semantic memory deficiency over time. The ability to read and write can also be impaired if there are irregularities between pronunciation and spelling. However, repetition and motor speech is relatively preserved.
The logopenic variant involves impairments in word retrieval, sentence repetition, and phonological paraphasias, comparable to
conduction aphasia
Conduction aphasia, also called associative aphasia, is an uncommon form of difficulty in speaking (aphasia). It is caused by damage to the parietal lobe of the brain. An acquired language disorder, it is characterised by intact auditory comprehe ...
. Compared to the semantic variant, single word comprehension and naming is spared, however, sentence comprehension presents difficulty because of length and grammatical complexity. Speech will include incomplete words, hesitations preceding content words, and repetition.
However, these PPA subtypes differ from similar aphasias, as these subtypes do not occur acutely following trauma to the brain, such as following a stroke, due to differing functional and structural neuroanatomical patterns of involvement and the progressive nature of the disease.
Treatment
Due to the progressive, continuous nature of the disease, improvement over time seldom occurs in patients with PPA as it often does in patients with aphasias caused by trauma to the brain.
In terms of medical approaches to treating PPA, there are currently no drugs specifically used for patients with PPA, nor are there any specifically designed interventions for PPA. A large reason for this is the limited research that has been done on this disease. However, in some cases, patients with PPA are prescribed the same drugs Alzheimer's patients are normally prescribed.
The primary approach to treating PPA has been with behavioral treatment, with the hope that these methods can provide new ways for patients to communicate in order to compensate for their deteriorated abilities.
Speech therapy can assist an individual with strategies to overcome difficulties. There are three very broad categories of therapy interventions for aphasia: restorative therapy approaches, compensatory therapy approaches, and social therapy approaches. Rapid and sustained improvement in speech and dementia in a patient with primary progressive aphasia utilizing off-label perispinal
etanercept
Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It ...
, an anti-
TNF
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
treatment strategy also used for
Alzheimer's
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...
, has been reported. A video depicting the patient's improvement was published in conjunction with the print article. These findings have not been independently replicated and remain controversial.
History
M. Marsel Mesulam coined the term primary progressive aphasia.
See also
*
Anomic aphasia
Anomic aphasia (also known as dysnomia, nominal aphasia, and amnesic aphasia) is a mild, fluent type of aphasia where individuals have word retrieval failures and cannot express the words they want to say (particularly nouns and verbs). By contra ...
*
Aphasiology
Aphasiology is the study of language impairment usually resulting from brain damage, due to neurovascular accident—hemorrhage, stroke—or associated with a variety of neurodegenerative diseases, including different types of dementia. These spec ...
*
Apraxia of speech
Apraxia of speech (AOS), also called verbal apraxia, is a speech sound disorder affecting an individual's ability to translate conscious speech plans into motor plans, which results in limited and difficult speech ability. By the definition of a ...
*
Speech-language pathology
*
Speech disorder
Speech disorders or speech impairments are a type of communication disorder in which normal speech is disrupted. This can mean stuttering, lisps, etc. Someone who is unable to speak due to a speech disorder is considered mute. Speech skills ar ...
*
Transcortical sensory aphasia Transcortical sensory aphasia (TSA) is a kind of aphasia that involves damage to specific areas of the temporal lobe of the brain, resulting in symptoms such as poor auditory comprehension, relatively intact repetition, and fluent speech with semant ...
References
Further reading
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External links
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{{CNS diseases of the nervous system
Aphasias
Alzheimer's disease
Cognitive disorders
Dementia
Learning disabilities