Regional glymphatic abnormality in behavioral variant frontotemporal dementia

Abstract

AbstractBackgroundThe pattern of glymphatic inflow overlaps with the geographic pattern of behavioral variant frontotemporal dementia (bvFTD). The glymphatic function has not yet been explored in bvFTD. The spatial correlation between regional glymphatic function and bvFTD remain unknown.MethodA total of 60 patients with bvFTD and 61 age‐ and sex‐matched healthy controls (HCs) were selected from two independent cohorts (discovery dataset from Xuanwu Hospital and replication dataset from the Frontotemporal Lobar Degeneration Neuroimaging Initiative study). All participant underwent neuropsychological assessment. Glymphatic measures evaluated from multimodal neuroimaging data, including choroid plexus volume, diffusion along perivascular space (DTI‐ALPS) index, and coupling between blood‐oxygen‐level‐dependent signals and cerebrospinal fluid signals (BOLD‐CSF coupling), were compared between the two groups. To evaluate glymphatic regional function, DTI‐ALPS and BOLD‐CSF coupling were further divided into anterior, middle, and posterior parts. BvFTD‐related metabolic pattern was identified using spatial covariance analysis based on [l8F]‐FDG‐PET.ResultPatients with bvFTD showed higher choroid plexus volume (P < 0.001); middle DTI‐ALPS (P < 0.001); and weaker anterior BOLD‐CSF coupling (P < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI‐ALPS was negatively associated with the expression of the bvFTD‐related metabolic pattern (r = ‐0.51, P = 0.029) and positively related with regional standardized uptake value ratios of [l8F]‐FDG‐PET in bvFTD‐related brain regions (r = 0.44–0.60, P range: 0.008–0.039). Worse glymphatic function is associated with more severe global cognition decline, disease severity, and neuropsychiatric symptoms. In addition, anterior DTI‐ALPS was higher than posterior DTI‐ALPS (P < 0.001), whereas anterior BOLD‐CSF coupling was lower than posterior BOLD‐CSF coupling (P < 0.001).ConclusionOur findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD.