Vascular dysfunction in behavior‐variant frontotemporal dementia

Abstract

AbstractBackgroundThe vascular disturbance was recently found in a postmortem study of frontotemporal dementia (FTD), but whether vascular dysfunction exists in the early stage of FTD remains elusive. The study aimed to explore whether there was evidence of vascular dysfunction in FTD and its relationship with central neurodegeneration and the clinical outcome.MethodTwenty patients with behavior frontotemporal dementia (bvFTD) were enrolled and underwent assessment of peripheral plasma vascular markers, positron emission tomography/magnetic resonance imaging, and neuropsychological examinations. Group difference was tested using the student’s t‐test and Mann‐Whitney U test. Partial correlation analysis was implemented using age and sex as covariates to explore the association between peripheral vascular markers, neuroimaging, and clinical measures.ResultAll four factors including matrix metalloproteinases‐1(MMP‐1), matrix metalloproteinases‐3 (MMP‐3), Osteopontin, and pentraxin‐3 are increased in the FTD group. The plasma level of MMP‐1 was negatively correlated with the gray matter metabolism of the prefrontal cortex (r = ‐0.5119, p = 0.0210) and the anterior cingulate cortex (r = ‐0.4685, p = 0.0269). MMP‐3 was negatively correlated with the gray matter metabolism of the anterior temporal cortex (r = ‐0.4650, p = 0.0388). Pentraxin‐3 was negatively correlated with age at sampling (r = ‐0.5024, p = 0.0240) and age at onset (r = ‐0.5693, p = 0.0088). No other significant associations were found in other vascular cytokines and clinical measures.ConclusionThe vascular disturbance was found in patients with bvFTD and associated with the disease‐specific neurodegeneration pattern, indicating vascular dysfunction and perturbance of the BBB participation in the pathogenesis of FTD. The vascular pathway might be a promising target for future potential therapy.