Frontal Cerebral Blood Flow Deficits in Behavioral Variant Frontotemporal Dementia: Associations With Clinical Symptoms, Peripheral Vascular Biomarkers, and Neuroimaging Measures

AIMS: This study aimed to characterize regional cerebral blood flow (CBF) alterations in behavioral variant frontotemporal dementia (bvFTD), examine their associations with clinical symptoms and peripheral vascular/synaptic biomarkers, evaluate spatial concordance with gray matter volume (GMV) loss and glucose hypometabolism, and explore CBF's mediating role between biomarkers and clinical outcomes. METHODS: F-FDG PET, and structural MRI. Plasma vascular (VEGFA, PDGF-BB) and synaptic (NPTXR, NPTX2) biomarkers were measured via the Olink platform. Statistical analyses included group comparisons, ROC analysis, multiple linear regression, and mediation analysis. RESULTS: Compared with normal controls, bvFTD patients exhibited significantly reduced CBF in both frontal and temporal regions, which showed regional spatial concordance with GMV and FDG uptake in corresponding areas. Frontal CBF demonstrated good diagnostic accuracy and was significantly associated with multiple clinical measures including MMSE, MoCA, ADL, and behavioral scales, as well as with peripheral vascular and synaptic biomarkers. Exploratory mediation analyses suggested statistical indirect associations linking peripheral vascular biomarkers to clinical symptoms through frontal CBF and linking frontal CBF to behavioral outcomes through frontal GMV. CONCLUSIONS: BvFTD is characterized by frontotemporal hypoperfusion, with frontal CBF closely associated with cognitive, behavioral, and functional impairment. The regional concordance of ASL-derived CBF with gray matter atrophy and glucose hypometabolism supports its potential role as an accessible, non-invasive, and radiation-free complementary neuroimaging biomarker. The mediation findings should be considered hypothesis-generating because they did not remain significant after FDR correction and require validation in larger longitudinal studies.