Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases presenting with insidious and relentless language impairment. Three main PPA variants have been described: the non-fluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). At the time of diagnosis, patients and their families’ main question pertains to prognosis and evolution, but very few data exist to support clinicians’ claims. The objective of this study was to review the current literature on the longitudinal changes in cognition, behaviours, and functional abilities in the three main PPA variants. A comprehensive review was undertaken via a search on PUBMED and EMBASE. Two authors independently reviewed a total of 65 full-text records for eligibility. A total of 14 group studies and one meta-analysis were included. Among these, eight studies included all three PPA variants. Eight studies were prospective, and the follow-up duration was between one and five years. Overall, svPPA patients showed more behavioural disturbances both at baseline and over the course of the disease. Patients with lvPPA showed a worse cognitive decline, especially in episodic memory, and faster progression to dementia. Finally, patients with nfvPPA showed the most significant losses in language production and functional abilities. Data regarding the prodromal and last stages of PPA are still missing and studies with a longer follow-up observation period are needed.

Knowledge on the natural history of the three main variants of primary progressive aphasia (PPA) is lacking, particularly regarding mortality. Moreover, advanced stages and end of life issues are rarely discussed with caregivers and families at diagnosis, which can cause more psychological distress. We analyzed data from 83 deceased patients with a diagnosis of PPA. We studied survival in patients with a diagnosis of logopenic variant (lvPPA), semantic variant (svPPA), or non-fluent variant (nfvPPA) and examined causes of death. From medical records, we retrospectively collected data for each patient at several time points spanning five years before the first visit to death. When possible, interviews were performed with proxies of patients to complete missing data. Results showed that survival from symptom onset and diagnosis was significantly longer in svPPA than in lvPPA (p = 0.002) and nfvPPA (p < 0.001). No relevant confounders were associated with survival. Mean survival from symptom onset was 7.6 years for lvPPA, 7.1 years for nfvPPA, and 12 years for svPPA. The most common causes of death were natural cardio-pulmonary arrest and pneumonia. Aspiration pneumonia represented 23% of deaths in nfvPPA. In conclusion, this pilot study found significant differences in survival between the three variants of PPA with svPPA showing the longest and nfvPPA showing more neurologically-related causes of death.

The finger-to-nose test is routinely performed during the clinical assessment of patients with cognitive impairments. Although widely known to screen for cerebellar dysfunction by unmasking appendicular ataxia, we have found that this test could also be interpreted from a cognitive perspective. We describe two typical signs observed at the finger-to-nose test in Alzheimer's disease (AD) patients: the "second finger syndrome" and the "distal pressure sign". By retrospectively reviewing the medical records 461 patients followed at our academic memory clinic, we found that these signs are commonplace in AD, but not in vascular dementia or subjective cognitive impairment.

Background: Primary progressive aphasias (PPAs) are a group of neurodegenerative disorders characterized by an insidious and progressive language impairment. Clinical expression and underlying pathology remain highly heterogeneous. To date, there is a lack of knowledge on the natural history of each of the three main variants, particularly mortality. Moreover, advanced stages and end of life issues are rarely discussed with caregivers and families at diagnosis. In turn, this can cause additional psychological distress.We studied the natural history of the three main variants of PPA. More specifically, we focused on mortality and end of life issues in an attempt to better prepare patients and their families. Method:We retrospectively studied all deceased patients with a diagnosis of PPA that had been followed at our tertiary memory clinic over the past twenty years (n=83).Clinical data included age of onset of symptoms, duration of illness, age at death and specific cause of death.Result: Age at death was similar across all three PPA variants but there was less variability in the non-fluent variant (nfvPPA) group (M=76.6, SD=6.2) than in the semantic variant (svPPA; M=74.1, SD=8.5) or the logopenic variant (lvPPA; M=76.1, SD=9.1) groups. Age at onset of symptoms was earlier for svPPA participants (M=64.5, SD=8.3) then for the two other variants (lvPPA: M=69.3, SD= 10.7; nfvPPA: M=70.4, SD=6.3).Consequently, duration of the disease (number of years between symptoms' onset and death) was longer for svPPA participants (M=9.6, SD=3.0) than for nfvPPA and lvPPA participants (respectively M=6.2, SD=2.1 and M=7.0, SD=2.9). Surprisingly, cause of death was unknown for most of the participants. When available (n=15), it included sepsis (n=6), respiratory failure (n=4), neoplasia (n=3) and stroke (n=2), and. There were no differences in causes of death among PPA variants. Conclusion:Despite similar age of death across PPA variants, disease duration was longer in the svPPA. Causes of death per se were similar among PPAs. Future studies should include more participants with better emphasis on causes of death. Nonetheless, our study provides useful information about the natural history of the common variants of PPA.

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