Semantic dementia, progressive non-fluent aphasia and their association with amyotrophic lateral sclerosis

Saxon, Jennifer A.; Harris, Jennifer; Thompson, James C.; Jones, Matthew; Richardson, Anna; Langheinrich, Tobias; Neary, David; Mann, David; Snowden, Julie S.

doi:10.1136/jnnp-2016-314912

Cited by 31 publications

(22 citation statements)

References 6 publications

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“…Furthermore the incidence of bv-FTD in combination with ALS is higher than that of the language subtypes of FTLD. 48 The presence of a cognitive disease continuum between bv-FTD and ALS could be corroborated when trajectories of cognitive deterioration are similar between the disorders. A relatively low number of longitudinal studies, however, prevented a meta-analysis of the course of cognitive decline in ALS.…”

Section: Comparison Of the Cognitive Profiles Of Bv-ftd And Alsmentioning

confidence: 97%

The cognitive profile of behavioural variant FTD and its similarities with ALS: a systematic review and meta-analysis

Beeldman

Raaphorst

Twennaar

et al. 2018

J Neurol Neurosurg Psychiatry

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Approximately 30% of patients with amyotrophic lateral sclerosis (ALS) have cognitive impairment and 8%-14% fulfil the criteria for behavioural variant frontotemporal dementia (bv-FTD). The cognitive profiles of ALS and bv-FTD have been reported to be comparable, but this has never been systematically investigated. We aimed to determine the cognitive profile of bv-FTD and examine its similarities with that of ALS, to provide evidence for the existence of a cognitive disease continuum encompassing bv-FTD and ALS. We therefore systematically reviewed neuropsychological studies on bv-FTD patients and healthy volunteers. Neuropsychological tests were divided in 10 cognitive domains and effect sizes were calculated for all domains and compared with the cognitive profile of ALS by means of a visual comparison and a Pearson's correlation coefficient. We included 120 studies, totalling 2425 bv-FTD patients and 2798 healthy controls. All cognitive domains showed substantial effect sizes, indicating cognitive impairment in bv-FTD patients compared to healthy controls. The cognitive domains with the largest effect sizes were social cognition, verbal memory and fluency (1.77-1.53). The cognitive profiles of bv-FTD and ALS (10 cognitive domains, 1287 patients) showed similarities on visual comparison and a moderate correlation 0.58 (p=0.13). When social cognition, verbal memory, fluency, executive functions, language and visuoperception were considered, i.e. the cognitive profile of ALS, Pearson's was 0.73 (p=0.09), which raised to 0.92 (p=0.03), when language was excluded in this systematic analysis of patients with a non-language subtype of FTD. The cognitive profile of bv-FTD consists of deficits in social cognition, verbal memory, fluency and executive functions and shows similarities with the cognitive profile of ALS. These findings support a cognitive continuum encompassing ALS and bv-FTD.

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Section: Comparison Of the Cognitive Profiles Of Bv-ftd And Alsmentioning

confidence: 97%

The cognitive profile of behavioural variant FTD and its similarities with ALS: a systematic review and meta-analysis

Beeldman

Raaphorst

Twennaar

et al. 2018

J Neurol Neurosurg Psychiatry

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“…FTLD disorders as a whole affect men and women equally . In patients with accompanying ALS, however, there is a significant male bias . Moreover, the presence of ALS influences the likelihood of one clinical syndrome rather than another.…”

Section: Demographics and Neurologymentioning

confidence: 99%

“…It is most often seen in combination with bvFTD. An association with SD and PNFA can occur but it is rare .…”

Section: Demographics and Neurologymentioning

confidence: 99%

Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype

2017

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Frontotemporal Lobar Degeneration (FTLD) is a clinically, pathologically and genetically heterogeneous group of disorders that affect principally the frontal and temporal lobes of the brain. There are three major associated clinical syndromes, behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA); three principal histologies, involving tau, TDP-43 and FUS proteins; and mutations in three major genes, MAPT, GRN and C9orf72, along with several other less common gene mutations. All three clinical syndromes can exist separately or in combination with Amyotrophic Lateral Sclerosis (ALS). SD is exclusively a TDP-43 proteinopathy, and PNFA may be so, with both showing tight clinical, histological and genetic inter-relationships. bvFTD is more of a challenge with overlapping histological and genetic features, involvement of any of the three aggregating proteins, and changes in any of the three major genes. However, when ALS is present, all cases show a clear histological phenotype with TDP-43 aggregated proteins, and familial forms are associated with expansions in C9orf72. TDP-43 and FUS are nuclear carrier proteins involved in the regulation of RNA metabolism, whereas tau protein - the product of MAPT - is responsible for the assembly/disassembly of microtubules, which are vital for intracellular transport. Mutations in TDP-43 and FUS genes are linked to clinical ALS rather than FTLD (with or without ALS), suggesting that clinical ALS may be a disorder of RNA metabolism. Conversely, the protein products of GRN and C9orf72, along with those of the other minor genes, appear to form part of the cellular protein degradation machinery. It is possible therefore that FTLD is a reflection of dysfunction within lysosomal/proteasomal systems resulting in failure to remove potentially neurotoxic (TDP-43 and tau) aggregates, which ultimately overwhelm capacity to function. Spread of aggregates along distinct pathways may account for the different clinical phenotypes, and patterns of progression of disease.

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“…The major clinical syndromes involve personality and behavioural changes (behavioural variant frontotemporal dementia, or bvFTD) or language alterations of a fluent (semantic dementia) or nonfluent (progressive nonfluent aphasia) nature . All three syndromes can be accompanied by amyotrophic lateral sclerosis (ALS), although the combination of bvFTD+ALS is most common . Although the disease mechanisms underlying FTLD remain unknown, genetic associations may provide clues to pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

The role of lysosomes and autophagosomes in frontotemporal lobar degeneration

Bain

Davidson

Robinson

et al. 2018

Neuropathology Appl Neurobio

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Semantic dementia, progressive non-fluent aphasia and their association with amyotrophic lateral sclerosis

Cited by 31 publications

References 6 publications

The cognitive profile of behavioural variant FTD and its similarities with ALS: a systematic review and meta-analysis

The cognitive profile of behavioural variant FTD and its similarities with ALS: a systematic review and meta-analysis

Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype

The role of lysosomes and autophagosomes in frontotemporal lobar degeneration

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