期刊
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
卷 91, 期 9, 页码 975-984出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jnnp-2020-322987
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资金
- UK Medical Research Council
- Italian Ministry of Health
- Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant
- Canadian Institutes of Health Research operating grant [MOP 327387]
- Weston Brain Institute
- NIHR Queen Square Dementia Biomedical Research Unit
- NIHR UCL/H Biomedical Research Centre
- Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility
- MRC Clinician Scientist Fellowship [MR/M008525/1]
- NIHR Rare Disease Translational Research Collaboration [BRC149/NS/MH]
- MRC UK GENFI grant [MR/M023664/1]
- Bluefield Project
- Alzheimer's Society PhD Studentship [AS-PhD-2015-005]
- Medical Research Council
- Wellcome Trust [103848]
- NIHR Cambridge Biomedical Research Centre
- Italian Ministry of Health [NET2011-02346784]
- Association for frontotemporal Dementias Research Grant 2009
- ZonMw Memorabel project [733050103, 733050813]
- Italian Ministry of Health, Ricerca Corrente
- JPND Prefrontals Swedish Research Council (VR) [529-2014-7504]
- Swedish Research Council (VR) [2015-02926, 201802754]
- Swedish FTD Initiative Schorling Foundation
- Swedish Brain Foundation
- Swedish Alzheimer Foundation
- Stockholm County Council ALF
- Karolinska Institutet Doctoral Funding
- StratNeuro, Swedish Demensfonden
- MRC [MC_U105597119, MC_UU_00005/12, MR/K010395/1] Funding Source: UKRI
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, preclinicalMAPTcarriers endorsed worse mood and sleep symptoms, andC9orf72carriers endorsed marginally greater abnormal behaviours. PreclinicalGRNcarriers 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.
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