The uncinate fasciculus in frontotemporal dementia subtypes: A systematic review and meta-analysis of diffusion-tensor imaging studies

BackgroundFrontotemporal dementia (FTD) is a leading cause of early-onset neurodegeneration with selective frontal and temporal lobe degeneration. Despite well-characterized gray and white matter atrophy patterns across FTD subtypes, the extent of degeneration of the uncinate fasciculus (UF) tract has not been systematically quantified across FTD subtypes.ObjectiveTo compare uncinate fasciculus fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity between frontotemporal dementia subtypes and healthy controls.MethodsWe systematically searched PubMed, Scopus, and Web of Science and performed a random-effects meta-analysis of diffusion tensor imaging studies published between 2011 and October 2025 according to PRISMA 2020 guidelines.ResultsWe systematically reviewed 11 studies and performed a meta-analysis of 540 participants across 10 studies. We found that all FTD subtypes demonstrated significant degeneration of the UF compared to controls. The greatest effect sizes were observed when comparing the left UF between the semantic variant primary progressive aphasia (svPPA) and controls (FA: SMD = -2.5396, 95% CI: -3.7914, -1.2878, p < 0.0001; RD: SMD = 2.2414, 95% CI:1.7972, 2.6855, p < 0.0001; AD: SMD = 1.9831, 95% CI: 1.1434, 2.8227, p < 0.0001; MD: SMD = 2.5268, 95% CI: 1.9993, 3.0542, p < 0.0001), while the behavioral variant (bvFTD) showed the largest reduction in right UF fractional anisotropy. Within-group analyses revealed significant left-right asymmetry in svPPA and non-fluent aphasia (nfvPPA), with greater left UF involvement, while bvFTD and controls showed no hemispheric differences.ConclusionsWe highlight the UF as a promising tract for understanding disease mechanisms and developing imaging biomarkers in FTD.