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The Benson Complex Figure Test detects deficits in visuoconstruction and visual...

Jiskoot, Lize C.; Russell, Lucy L.; Peakman, Georgia; Convery, Rhian S.; Greaves, Caroline V.; Bocchetta, Martina; Poos, Jackie M.; Seelaar, Harro

Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation carriers, a...


The Benson Complex Figure Test detects deficits in visuoconstruction and visual...

Jiskoot, Lize C.; Russell, Lucy L.; Peakman, Georgia; Convery, Rhian S.; Greaves, Caroline V.; Bocchetta, Martina; Poos, Jackie M.; Seelaar, Harro

Objective: Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation ...


Association of rare APOE missense variants V236E and R251G with risk of Alzheim...

Le Guen, Yann; Belloy, Michael E.; Grenier-Boley, Benjamin; de Rojas, Itziar; Castillo-Morales, Atahualpa; Jansen, Iris; Nicolas, Aude

Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide crit...


Longitudinal cognitive changes in genetic frontotemporal dementia within the GE...

Poos, Jackie M.; MacDougall, Amy; van den Berg, Esther; Jiskoot, Lize C.; Papma, Janne M.; van der Ende, Emma L.; Seelaar, Harro; Russell, Lucy L.

Background and objectives: Disease-modifying therapeutic trials for genetic frontotemporal dementia (FTD) are underway, but sensitive cognitive outcome measures are lacking. The aim of this study was to identify such cognitive tests in early stage FTD by investigating cognitive decline in a large cohort of genetic FTD pathogenic variant carriers and by investigating whether gene-specific differences are moderat...


A data-driven disease progression model of fluid biomarkers in genetic frontote...

van der Ende, Emma L.; Bron, Esther E.; Poos, Jackie M.; Jiskoot, Lize C.; Panman, Jessica L.; Papma, Janne M.; Meeter, Lieke H.; Dopper, Elise G. P.

Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the ...


Elevated CSF and plasma complement proteins in genetic frontotemporal dementia:...

van der Ende, Emma L.; Heller, Carolin; Sogorb-Esteve, Aitana; Swift, Imogen J.; McFall, David; Peakman, Georgia; Bouzigues, Arabella; Poos, Jackie M.

Background: Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers. Methods: We measured the complement proteins C1q and ...


Common variants in Alzheimer's disease and risk stratification by polygenic ris...

de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, Iris E.; Pedersen, Nancy L.; Stringa, Najada

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Her...


Clinical value of cerebrospinal fluid neurofilament light chain in semantic dem...

Meeter, Lieke H. H.; Steketee, Rebecca M. E.; Salkovic, Dina; Vos, Maartje E.; Grossman, Murray; McMillan, Corey T.; Irwin, David J.; Boxer, Adam L.

Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FT...


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