% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Tavares:153442,
      author       = {Tavares, Tamara Paulo and Mitchell, Derek G V and Coleman,
                      Kristy KL and Coleman, Brenda L and Shoesmith, Christen L
                      and Butler, Christopher R and Santana, Isabel and Danek,
                      Adrian and Gerhard, Alexander and de Mendonca, Alexandre and
                      Borroni, Barbara and Tartaglia, Maria Carmela and Graff,
                      Caroline and Galimberti, Daniela and Tagliavini, Fabrizio
                      and Moreno, Fermin and Frisoni, Giovanni and Rowe, James
                      Benedict and Levin, Johannes and Van Swieten, John Cornelis
                      and Otto, Markus and Synofzik, Matthis and Sanchez-Valle,
                      Raquel and Vandenberghe, Rik and Laforce, Robert Jr and
                      Ghidoni, Roberta and Sorbi, Sandro and Ducharme, Simon and
                      Masellis, Mario and Rohrer, Jonathan and Finger, Elizabeth},
      title        = {{E}arly symptoms in symptomatic and preclinical genetic
                      frontotemporal lobar degeneration},
      journal      = {Journal of neurology, neurosurgery, and psychiatry},
      volume       = {91},
      number       = {9},
      issn         = {1468-330X},
      address      = {London},
      publisher    = {BMJ Publishing Group},
      reportid     = {DZNE-2020-01439},
      pages        = {975 - 984},
      year         = {2020},
      abstract     = {Objectives The clinical heterogeneity of frontotemporal
                      dementia (FTD) complicates identification of biomarkers for
                      clinical trials that may be sensitive during the
                      prediagnostic stage. It is not known whether cognitive or
                      behavioural changes during the preclinical period are
                      predictive of genetic status or conversion to clinical FTD.
                      The first objective was to evaluate the most frequent
                      initial symptoms in patients with genetic FTD. The second
                      objective was to evaluate whether preclinical mutation
                      carriers demonstrate unique FTD-related symptoms relative to
                      familial mutation non-carriers.Methods The current study
                      used data from the Genetic Frontotemporal Dementia
                      Initiative multicentre cohort study collected between 2012
                      and 2018. Participants included symptomatic carriers (n=185)
                      of a pathogenic mutation in chromosome 9 open reading frame
                      72 (C9orf72), progranulin (GRN) or microtubule-associated
                      protein tau (MAPT) and their first-degree biological family
                      members (n=588). Symptom endorsement was documented using
                      informant and clinician-rated scales.Results The most
                      frequently endorsed initial symptoms among symptomatic
                      patients were apathy $(23\%),$ disinhibition $(18\%),$
                      memory impairments $(12\%),$ decreased fluency $(8\%)$ and
                      impaired articulation $(5\%).$ Predominant first symptoms
                      were usually discordant between family members. Relative to
                      biologically related non-carriers, preclinical MAPT carriers
                      endorsed worse mood and sleep symptoms, and C9orf72 carriers
                      endorsed marginally greater abnormal behaviours. Preclinical
                      GRN carriers endorsed less mood symptoms compared with
                      non-carriers, and worse everyday skills.Conclusion
                      Preclinical mutation carriers exhibited neuropsychiatric
                      symptoms compared with non-carriers that may be considered
                      as future clinical trial outcomes. Given the heterogeneity
                      in symptoms, the detection of clinical transition to
                      symptomatic FTD may be best captured by composite indices
                      integrating the most common initial symptoms for each
                      genetic group},
      keywords     = {Adult / C9orf72 Protein: genetics / Female / Frontotemporal
                      Dementia: diagnosis / Frontotemporal Dementia: genetics /
                      Heterozygote / Humans / Male / Middle Aged / Mutation /
                      Prodromal Symptoms / Progranulins: genetics / tau Proteins:
                      genetics},
      cin          = {U Clinical Researchers - München / AG Gasser 1 / AG
                      Höglinger 2 / Clinical Dementia Research München},
      ddc          = {610},
      cid          = {I:(DE-2719)7000003 / I:(DE-2719)1210000 /
                      I:(DE-2719)1111015 / I:(DE-2719)1111016},
      pnm          = {344 - Clinical and Health Care Research (POF3-344) / 345 -
                      Population Studies and Genetics (POF3-345)},
      pid          = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-345},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC7611534},
      pubmed       = {pmid:32769115},
      doi          = {10.1136/jnnp-2020-322987},
      url          = {https://pub.dzne.de/record/153442},
}