P1-048 Natural history of primary progressive aphasia

Mutations in the TANK-binding kinase (TBK1) gene have been shown to cause frontotemporal dementia (FTLD) and amyotrophic lateral sclerosis (ALS). The phenotype is highly variable and has been associated with behavioural variant FTD, primary progressive aphasia and pure amyotrophic lateral sclerosis. We describe the clinical, anatomical and pathological features of a patient with onset of a corticobasal syndrome (CBS)/primary progressive aphasia overlap aged 59. The patient presented with progressive speech difficulties and later developed an asymmetric akinetic-rigid syndrome. Neuroimaging showed asymmetrical frontal atrophy, predominantly affecting the right side. There was a strong family history of neurodegenerative disease with 4/7 siblings developing either dementia or ALS in their 50’s-60’s. Following death at age 71, post mortem examination revealed FTLD TDP-43 type A pathology. Genetic screening did not reveal a mutation in the progranulin, microtubule-associated protein tau or C9orf72 genes. However exome sequencing revealed a novel E703X mutation in the TBK1 gene. Although segregation data was not available, this loss of function mutation is highly likely to be pathogenic. In conclusion, we show that TBK1 can be a cause of an atypical parkinsonian syndrome and screening for TBK1 should be considered in CBS patients with a family history of dementia, ALS or CBS.

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The natural history of primary progressive aphasia: beyond aphasia

Journal of Neurology ◽

10.1007/s00415-021-10689-1 ◽

2021 ◽

Author(s):

Hulya Ulugut ◽

Simone Stek ◽

Lianne E. E. Wagemans ◽

Roos J. Jutten ◽

Maria Antoinette Keulen ◽

...

Keyword(s):

Diagnostic Criteria ◽

Primary Progressive Aphasia ◽

Cognitive Test ◽

Motor Deficits ◽

Behavioral Disturbances ◽

Progressive Aphasia ◽

Clinical Criteria ◽

Primary Progressive ◽

Clinical Onset ◽

History Of

Abstract Introduction Primary progressive aphasia (PPA) is divided into three prototypical subtypes that are all characterized by their single core symptom of aphasia. Although later in their course, other cognitive, behavioral, and motor domains may become involved, little is known about the progression profile of each subtype relative to the other subtypes. Methods In this longitudinal retrospective cohort study, based on the recent biomarker-supported diagnostic criteria, 24 subjects diagnosed with semantic variant (svPPA), 22 with non-fluent variant (nfvPPA), and 18 with logopenic variant (lvPPA) were collected and followed up for 1–6 years. Symptom distribution, cognitive test and neuropsychiatric inventory scores, and progression into another syndrome were assessed. Results Over time, lvPPA progressed with broader language problems (PPA-extended) and nfvPPA progressed to mutism, whereas semantic impairment remained the major problem in svPPA. Apart from linguistic problems, svPPA developed pronounced behavioral disturbances, whereas lvPPA exhibited a greater cognitive decline. By contrast, in nfvPPA motor deficits were more common. Furthermore, within 5 years (IQR = 2.5) after clinical onset, 65.6% of the patients additionally fulfilled the clinical criteria for another neurodegenerative syndrome (PPA-plus). Fourteen out of 24 (58%) svPPA patients additionally met the diagnostic criteria of behavioral variant frontotemporal dementia (5.1 years, IQR = 1.1), whereas the clinical features of 15/18 (83%) lvPPA patients were consistent with Alzheimer disease dementia (4.5 years IQR = 3.4). Furthermore, 12/22 (54%) of the subjects with the nfvPPA progressed to meet the diagnostic criteria of corticobasal syndrome, progressive supranuclear palsy, or motor neuron disease (5.1 years IQR = 3.4). Discussion Despite aphasia being the initial and unique hallmark of the syndrome, our longitudinal results showed that PPA is not a language limited disorder and progression differs widely for each subtype, both with respect to the nature of symptoms and disease duration.

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Survival in the Three Common Variants of Primary Progressive Aphasia: A Retrospective Study in a Tertiary Memory Clinic

Brain Sciences ◽

10.3390/brainsci11091113 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1113

Author(s):

Maud Tastevin ◽

Monica Lavoie ◽

Justine de la Sablonnière ◽

Julie Carrier-Auclair ◽

Robert Jr. Laforce

Keyword(s):

Symptom Onset ◽

Causes Of Death ◽

Primary Progressive Aphasia ◽

Progressive Aphasia ◽

Primary Progressive ◽

Common Causes ◽

Life Issues ◽

History Of ◽

Advanced Stages ◽

End Of Life Issues

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.

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