• Elise G P Dopper, Vicky Chalos, Eidrees Ghariq, Tom den Heijer, Anne Hafkemeijer, Lize C Jiskoot, Inge de Koning, Harro Seelaar, Rick van Minkelen, Matthias J P van Osch, Serge A R B Rombouts, and John C van Swieten.
• 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.
• Neuroimage Clin. 2016 Jan 1; 12: 460-5.

ObjectiveFrontotemporal 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).MethodsHealthy 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).ResultsGRN 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.InterpretationWe 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.

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