RT Journal Article
SR Electronic
T1 Early symptoms in symptomatic and preclinical genetic frontotemporal lobar degeneration
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 975
OP 984
DO 10.1136/jnnp-2020-322987
VO 91
IS 9
A1 Tavares, Tamara Paulo
A1 Mitchell, Derek G V
A1 Coleman, Kristy KL
A1 Coleman, Brenda L
A1 Shoesmith, Christen L
A1 Butler, Christopher R
A1 Santana, Isabel
A1 Danek, Adrian
A1 Gerhard, Alexander
A1 de Mendonca, Alexandre
A1 Borroni, Barbara
A1 Tartaglia, Maria Carmela
A1 Graff, Caroline
A1 Galimberti, Daniela
A1 Tagliavini, Fabrizio
A1 Moreno, Fermin
A1 Frisoni, Giovanni B
A1 Rowe, James Benedict
A1 Levin, Johannes
A1 Van Swieten, John Cornelis
A1 Otto, Markus
A1 Synofzik, Matthis
A1 Sanchez-Valle, Raquel
A1 Vandenberghe, Rik
A1 Laforce, Robert Jr
A1 Ghidoni, Roberta
A1 Sorbi, Sandro
A1 Ducharme, Simon
A1 Masellis, Mario
A1 Rohrer, Jonathan D
A1 Finger, Elizabeth
A1 
YR 2020
UL http://jnnp.bmj.com/content/91/9/975.abstract
AB 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.Data may be obtained from a third party and are not publicly available. The data for this study were obtained from the GENFI data freeze 4. Further details on the GENFI protocol, cohorts and data policies can be found at http://genfi.org.uk/samples.html.