Beyond aphasia: Natural history of the aphasia onset dementia syndromes

Abstract

AbstractBackgroundAphasic syndromes caused by neurodegenerative disease are known as Primary Progressive Aphasias (PPA). The most recent consensus criteria have classified PPA into the non‐fluent variant (nfPPA), semantic variant (svPPA) and the logopenic variant (lvPPA). Few longitudinal studies have explored the prognosis of patients with PPA. This study aims to give an overview of the clinical profile divided into different domains, the progression into other diagnoses and mortality of the different subtypes of PPA.MethodTwenty‐two patients diagnosed with nfPPA, 24 with svPPA and 18 with lvPPA between 2011 and 2019 were retrospectively collected and followed‐up for a maximum of over 6 years. Biomarkers and neuroimaging were acquired at baseline. Reported additional symptoms, neurological signs and outcomes on different neuropsychological tests during follow‐up period were collected and compared for baseline and longitudinal results. Kaplan‐ Meier survival analysis was performed for mortality rate.ResultAs expected, a language disorder was the main problem of all PPA patients at the first assessment. However, over the disease course, the subtypes exhibited a different progression pattern. Behavioural problems were prominent in svPPA whereas patients with lvPPA exhibited a greater executive and visuospatial dysfunction and episodic memory impairment (p<0.05). Unlike svPPA and lvPPA, nfPPA subjects presented a relatively pure aphasia profile initially. However, 50% of the subjects developed extrapyramidal and pyramidal signs within 4 years and progressed into other diagnoses such as corticobasal degeneration, progressive supranuclear palsy, motor neuron disease, behavioural variant frontotemporal dementia and Alzheimer’s disease. Furthermore, in this group the mortality rate was significantly higher in comparison to the other subtypes (median years 3.04 [1.06 – 5.62], p=0.001). By contrast, none of the svPPA patients progressed into another diagnosis whereas 78% of the lvPPA patients progressed to Alzheimer’s disease within 3 years (Figure 1).ConclusionTo our knowledge, this is the first study to determine the progression profiles and the entire course of the disease from the diagnosis to the death. Our results show that prognosis differs widely per PPA subgroup. Disclosing the risk of developing motor symptoms should be considered in the case of nfPPA.