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000281113 1001_ $$00000-0002-1151-6243$$aKancheva, Ivana Kirilova$$b0
000281113 245__ $$aCerebrovascular Reactivity at Rest and Its Association With Cognitive Function in People With Genetic Frontotemporal Dementia.
000281113 260__ $$aPhiladelphia, Pa.$$bWolters Kluwer$$c2025
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000281113 520__ $$aCerebrovascular reactivity (CVR) is an indicator of cerebrovascular health, and its signature in familial frontotemporal dementia (FTD) remains unknown. The primary aim was to investigate CVR in genetic FTD using an fMRI index of vascular contractility termed resting-state fluctuation amplitudes (RSFAs) and to assess whether RSFA differences are moderated by age. A secondary aim was to study the relationship between RSFA and cognition.Participants included presymptomatic and symptomatic C9orf72, GRN, and MAPT pathogenic variation carriers, along with noncarriers, from the prospective Genetic FTD Initiative cohort study. Cross-sectional differences in CVR were assessed using both component-based and voxel-level RSFA maps. To study disease progression-related effects, the moderating effect of age on differences between genetic status groups was analyzed using generalized linear models. The influence of RSFA, and its interaction with genetic status, on participants' cognitive function was also examined. All models were adjusted for sex, handedness, and scanning site and false discovery rate-corrected at p < 0.05.A total of 284 presymptomatic and 124 symptomatic sequence variation carriers, and 265 noncarriers, were included in the analysis (mean age 48.17 years, 55% female). Across the sample, symptomatic carriers exhibited lower RSFA and a greater age-related RSFA decline predominantly in the medial frontal (-0.07 standard units, p = 0.046, 95% CI -0.13 to -0.01) and posterior parietal (-0.06 standard units, p = 0.048, 95% CI -0.12 to 0.01) cortex, compared with presymptomatic carriers and noncarriers. RSFA was inversely correlated with age (-0.43 standard units, p < 0.001, 95% CI -0.48 to -0.37) and positively associated with cognitive function (0.09 standard units, p = 0.008, 95% CI 0.04-0.15), particularly in the prefrontal cortex, in sequence variation carriers across the sample, independent of disease stage.CVR impairment in genetic FTD has a predilection for the middle frontal and posterior cortex, and its preservation may yield a cognitive benefit for at-risk individuals. Although findings do not provide causality and warrant replication, they support the notion that vascular dysfunction in familial FTD may be a target for biomarker identification and disease-modifying efforts.
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000281113 650_7 $$2NLM Chemicals$$aC9orf72 Protein
000281113 650_7 $$2NLM Chemicals$$atau Proteins
000281113 650_7 $$2NLM Chemicals$$aMAPT protein, human
000281113 650_7 $$2NLM Chemicals$$aC9orf72 protein, human
000281113 650_7 $$2NLM Chemicals$$aProgranulins
000281113 650_7 $$2NLM Chemicals$$aGRN protein, human
000281113 650_2 $$2MeSH$$aHumans
000281113 650_2 $$2MeSH$$aMale
000281113 650_2 $$2MeSH$$aFemale
000281113 650_2 $$2MeSH$$aFrontotemporal Dementia: genetics
000281113 650_2 $$2MeSH$$aFrontotemporal Dementia: physiopathology
000281113 650_2 $$2MeSH$$aFrontotemporal Dementia: diagnostic imaging
000281113 650_2 $$2MeSH$$aFrontotemporal Dementia: psychology
000281113 650_2 $$2MeSH$$aMiddle Aged
000281113 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000281113 650_2 $$2MeSH$$aCognition: physiology
000281113 650_2 $$2MeSH$$aAged
000281113 650_2 $$2MeSH$$aC9orf72 Protein: genetics
000281113 650_2 $$2MeSH$$aCross-Sectional Studies
000281113 650_2 $$2MeSH$$atau Proteins: genetics
000281113 650_2 $$2MeSH$$aCerebrovascular Circulation: physiology
000281113 650_2 $$2MeSH$$aProgranulins: genetics
000281113 650_2 $$2MeSH$$aAdult
000281113 650_2 $$2MeSH$$aBrain: diagnostic imaging
000281113 650_2 $$2MeSH$$aBrain: physiopathology
000281113 650_2 $$2MeSH$$aBrain: blood supply
000281113 650_2 $$2MeSH$$aRest
000281113 7001_ $$00000-0002-0267-8590$$aBouzigues, Arabella$$b1
000281113 7001_ $$00000-0001-5023-5893$$aRussell, Lucy Louise$$b2
000281113 7001_ $$00000-0001-6300-6598$$aFoster, Phoebe H$$b3
000281113 7001_ $$00009-0006-5083-0901$$aFerry-Bolder, Eve$$b4
000281113 7001_ $$aVan Swieten, John C$$b5
000281113 7001_ $$00000-0002-1120-1858$$aJiskoot, Lize Corrine$$b6
000281113 7001_ $$00000-0003-1989-7527$$aSeelaar, Harro$$b7
000281113 7001_ $$00000-0001-7750-896X$$aSánchez-Valle, Raquel$$b8
000281113 7001_ $$00000-0002-2031-490X$$aLaforce, Robert$$b9
000281113 7001_ $$00000-0002-9949-2951$$aGraff, Caroline$$b10
000281113 7001_ $$00000-0002-9284-5953$$aGalimberti, Daniela$$b11
000281113 7001_ $$00000-0001-6237-2502$$aVandenberghe, Rik$$b12
000281113 7001_ $$00000-0002-0488-1453$$ade Mendonça, Alexandre$$b13
000281113 7001_ $$00000-0002-2171-1720$$aTiraboschi, Pietro$$b14
000281113 7001_ $$00000-0002-8114-9434$$aSantana, Isabel$$b15
000281113 7001_ $$00000-0002-8071-6062$$aGerhard, Alexander$$b16
000281113 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b17
000281113 7001_ $$00000-0002-0380-6670$$aSorbi, Sandro$$b18
000281113 7001_ $$00000-0003-4273-4267$$aOtto, Markus$$b19
000281113 7001_ $$00000-0002-7309-1113$$aDucharme, Simon$$b20
000281113 7001_ $$00000-0002-7502-9284$$aButler, Christopher$$b21
000281113 7001_ $$00000-0002-2508-5181$$aLe Ber, Isabelle$$b22
000281113 7001_ $$00000-0003-4461-7427$$aFinger, Elizabeth$$b23
000281113 7001_ $$00000-0002-5944-8497$$aTartaglia, Maria Carmela$$b24
000281113 7001_ $$00000-0002-6244-2096$$aMasellis, Mario$$b25
000281113 7001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b26
000281113 7001_ $$00000-0001-5200-3164$$aMoreno, Fermin$$b27
000281113 7001_ $$00000-0001-9340-9814$$aBorroni, Barbara$$b28
000281113 7001_ $$00000-0002-6155-8417$$aRohrer, Jonathan Daniel$$b29
000281113 7001_ $$avan der Weerd, Louise$$b30
000281113 7001_ $$00000-0001-7216-8679$$aRowe, James B$$b31
000281113 7001_ $$00000-0002-3178-6363$$aTsvetanov, Kamen$$b32
000281113 7001_ $$aConsortium, GENFI$$b33$$eCollaboration Author
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