A longitudinal study on changes in cerebral cortical gray matter volume in patients with persistent olfactory loss after upper respiratory tract infection

Yao Linyin; Zhao Wan; Guo Yichen; Sun Zhifu; Wang Jianhong; Yi Xiaoli

doi:10.3760/j.issn.1673-4777.2026.03.022

Abstract：Objective To investigate the longitudinal dynamic changes in cerebral gray matter volume in patients with persistent olfactory loss after upper respiratory tract infection(PURIPOL).Methods A total of 20 PURIPOL patients(8 males and 12 females,aged 41±11 years)with olfactory loss lasting more than 2 years who were treated at the olfactory and gustatory disorders diagnosis and treatment center of Beijing Anzhen Hospital,Capital Medical University from January 2018 to December 2024 were enrolled.Another 20 age-,gender-and education-matched healthy volunteers were recruited as the control group.Subjective and objective olfactory functions were evaluated by the Sniffin'sticks test(TDI score)and olfactory event-related potentials(oERPs),and cognitive function was screened by the mini-mental state examination(MMSE).Retrospective analysis was performed on the 3D-T1-weighted brain structural magnetic resonance imaging of PURIPOL patients at three stages:3-12 months,＞12-24 months and＞24 months after the onset of olfactory loss.Voxel-based morphometry(VBM)was used to compare the differences in gray matter volume between PURIPOL patients and the control group,and to observe the evolutionary law over time.Results The TDI score of the PURIPOL group was significantly lower than that of the control group[(5.7±3.1)vs(34.6±2.6)](P＜0.01).The oERPs of the PURIPOL group showed longer latencies and lower amplitudes of N1 and P2 waves than those of the control group(all P＜0.01).VBM analysis revealed that compared with the control group,the PURIPOL group had a significant reduction in gray matter volume in the right orbitofrontal cortex and left gyrus rectus at 3-12 months after olfactory loss;the gray matter volume in the right orbitofrontal cortex and bilateral gyrus rectus further decreased at＞12-24 months;and the scope of gray matter atrophy extended to the bilateral orbitofrontal cortex,bilateral gyrus rectus and right insula at＞24 months(FDR corrected,all P＜0.001).Conclusion Progressive reduction in gray matter volume exists in olfactory-related brain regions of PURIPOL patients,suggesting that long-term lack of olfactory input may lead to structural remodeling in the corresponding brain regions,which may be one of the important central mechanisms of persistent olfactory loss.