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Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results

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Mirza, Saira S 
Luciw, Nicholas 
Mutsaerts, Henri JMM 
Petr, Jan 


jats:titleAbstract</jats:title>jats:secjats:titleINTRODUCTION</jats:title>jats:pEffective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers.</jats:p></jats:sec>jats:secjats:titleMETHODS</jats:title>jats:pWe investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 jats:italicC9orf72</jats:italic>, 70 jats:italicGRN</jats:italic>, and 31 jats:italicMAPT</jats:italic> presymptomatic carriers and 158 non‐carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment.</jats:p></jats:sec>jats:secjats:titleRESULTS</jats:title>jats:pPerfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus asymptomatic carriers past their expected age of disease onset.</jats:p></jats:sec>jats:secjats:titleDISCUSSION</jats:title>jats:pCerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset.</jats:p></jats:sec>jats:secjats:titleHighlights</jats:title>jats:p<jats:list list-type="bullet"> jats:list-itemjats:pGray matter perfusion declines in at‐risk genetic frontotemporal dementia (FTD).</jats:p></jats:list-item> jats:list-itemjats:pRegional perfusion decline differs between at‐risk genetic FTD subgroups .</jats:p></jats:list-item> jats:list-itemjats:pHypoperfusion in the left thalamus is common across all presymptomatic groups.</jats:p></jats:list-item> jats:list-itemjats:pConverters exhibit greater right frontal hypoperfusion than non‐converters past their expected conversion date.</jats:p></jats:list-item> jats:list-itemjats:pCerebral hypoperfusion is a potential early biomarker of genetic FTD.</jats:p></jats:list-item> </jats:list></jats:p></jats:sec>


Publication status: Published

Funder: Weston Brain Institute; doi:

Funder: Deutsche Forschungsgemeinschaft; doi:

Funder: Saul A. Silverman Family Foundation

Funder: Canada International Scientific Exchange Program

Funder: Morris Kerzner Memorial Fund; doi:

Funder: European Union; doi:

Funder: University of Toronto Medical Science Open

Funder: Joseph Bazylewicz Fellowships

Funder: Swedish FTD Initiative Schörling Foundation

Funder: EU Joint Programme Neurodegenerative Disease Research‐GENFI‐PROX


presymptomatic biomarker, frontotemporal dementia, cerebral perfusion, arterial spin labeling

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Alzheimer's &amp; Dementia

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Canadian Institutes of Health Research (MOP‐327387, PJT‐175242)
Medical Research Council UK (MR/M023664/1)
Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198)
MRC Clinician Scientist Fellowship (MR/M008525/1)
NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH)
ZonMW Memorabel (733 051 042)
National Institute for Health Research Cambridge Biomedical Research Centre (NIHR203312)
Medical Research Council (MC_UU_00030/14, MR/T033371/1)
Instituto de Salud Carlos III (20/0448)
EU Joint Programme Neurodegenerative Disease Research Prefrontals Vetenskapsrådet (Dnr 529‐2014‐7504)
Vetenskapsrådet (2019‐0224, 2015‐02926, 2018‐02754)