Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study.

Autor:	Dopper EG; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Neurology, VU Medical Center, Amsterdam, The Netherlands., Chalos V; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands., Ghariq E; C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands., den Heijer T; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Neurology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands., Hafkemeijer A; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Methodology and Statistics, Institute of Psychology, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands., Jiskoot LC; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Neuropsychology, Erasmus Medical Center, Rotterdam, The Netherlands., de Koning I; Department of Neuropsychology, Erasmus Medical Center, Rotterdam, The Netherlands., Seelaar H; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands., van Minkelen R; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands., van Osch MJ; C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands., Rombouts SA; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Methodology and Statistics, Institute of Psychology, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands., van Swieten JC; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	NeuroImage. Clinical [Neuroimage Clin] 2016 Aug 03; Vol. 12, pp. 460-5. Date of Electronic Publication: 2016 Aug 03 (Print Publication: 2016).
DOI:	10.1016/j.nicl.2016.08.001
Abstrakt:	Objective: Frontotemporal dementia (FTD) is characterized by behavioral disturbances and language problems. Familial forms can be caused by genetic defects in microtubule-associated protein tau (MAPT), progranulin (GRN), and C9orf72. In light of upcoming clinical trials with potential disease-modifying agents, the development of sensitive biomarkers to evaluate such agents in the earliest stage of FTD is crucial. In the current longitudinal study we used arterial spin labeling MRI (ASL) in presymptomatic carriers of MAPT and GRN mutations to investigate early changes in cerebral blood flow (CBF). Methods: Healthy first-degree relatives of patients with a MAPT or GRN mutation underwent ASL at baseline and follow-up after two years. We investigated cross-sectional and longitudinal differences in CBF between mutation carriers (n = 34) and controls without a mutation (n = 31). Results: GRN mutation carriers showed significant frontoparietal hypoperfusion compared with controls at follow-up, whereas we found no cross-sectional group differences in the total study group or the MAPT subgroup. Longitudinal analyses revealed a significantly stronger decrease in CBF in frontal, temporal, parietal, and subcortical areas in the total group of mutation carriers and the GRN subgroup, with the strongest decrease in two mutation carriers who converted to clinical FTD during follow-up. Interpretation: We demonstrated longitudinal alterations in CBF in presymptomatic FTD independent of grey matter atrophy, with the strongest decrease in individuals that developed symptoms during follow-up. Therefore, ASL could have the potential to serve as a sensitive biomarker of disease progression in the presymptomatic stage of FTD in future clinical trials.
Databáze:	MEDLINE
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