Primary progressive aphasia

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, the symptoms that accompany PPA depend on what parts of the left hemisphere 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, PPAs have a clinical and pathological overlap with the frontotemporal lobar degeneration spectrum of disorders and Alzheimer's disease. Unlike those affected by Alzheimer's, people with PPA are generally able to maintain self sufficiency.

Currently, the specific causes for PPA and other degenerative brain disease similar to PPA are viewed as idiopathic (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, and positron emission tomography, have generally revealed abnormalities to be almost exclusively in the left hemisphere. 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 (FTLD), 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 progressive nonfluent aphasia (PNFA) being more commonly familial in nature than logopenic progressive aphasia (LPA) or semantic dementia (SD). Most patients with observed GRN mutations present clinical features of PNFA, but the phenotype can be atypical. 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. In the classical Mesulam criteria for primary progressive aphasia, there are two variants: a non fluent type PNFA and a fluent type SD. A third variant of primary progressive aphasia, LPA was then added, and is an atypical form of Alzheimer's disease. For PNFA, the core criteria for diagnosis include 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. Unlike those affected by Alzheimer's, people 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, 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. Rapid and sustained improvement in speech and dementia in a patient with primary progressive aphasia utilizing off label perispinal etanercept, an anti TNF treatment strategy also used for Alzheimer's, 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.

M. Marsel Mesulam coined the term primary progressive aphasia.