Abstract: Objective To identify the atrophy feature of hippocampal subregions in patients with white matter hyperintensity (WMH) and its correlation with cognitive dysfunction. Methods Patients with WMH admitted to Nanjing Drum Tower Hospital were consecutively and prospectively recruited from 2017 to 2019. The volunteers recruited in the outpatient department during the same period were enrolled as normal controls. All subjects underwent MRI scans, and received cognitive assessments according to MMSE and MoCA scores, then were divided into WMH without cognitive impairment (CI) group and WMH with CI group. FreeSurfer 6.0 software was used to segment the hippocampal subregions, and the volume of bilateral hippocampal tail,

subiculum, CA1, hippocampal fissure, presubiculum, parasubiculum, molecular layer, dentate

gyrus(DG), CA3, CA4, hippocampal fimbria and hippocampus amygdala transition area (HATA) were calculated. The volume of periventricular, deep and total WMH were also calculated. The volume of the total hippocampus and each hippocampal subregions were compared among the three groups. The relationship between the atrophy of hippocampal subregions and the volume of WMH was analyzed in all patients with WMH. Finally, the correlation between hippocampal subregion volume and cognitive domain dysfunction was analyzed in WMH with CI group. Results A total of 85 controls, 79 patients in WMH without CI group and 89 in WMH with CI group were enrolled in this study. Compared with the control group, the WMH without CI group showed significant atrophy in the right DG (P =0.006), CA3 (P =0.006) and CA4 (P =0.020); while the WMH with CI group showed a significant decline in the volume of the right subiculum (P =0.022), molecular layer (P =0.003), DG (P =0.001), CA3 (P =0.039), CA4 (P =0.003), and the bilateral fimbria (left P =0.004, right P =0.020). Among WMH patients, the volume of the right DG was negatively correlated with the total (r =-0.134, P =0.035) and periventricular WMH (r =-0.128, P =0.045) volume,and the volume of the right CA3 was also negatively correlated with the total (r =-0.149, P =0.020) and periventricular WMH volume (r =-0.139, P =0.029). In addition, in WMH with CI group, the volume of the right subiculum was positively correlated to the general cognitive function (r =0.315, P =0.004) and language function (r =0.318, P =0.006). Executive function was positively correlated with the volume of right molecular layer (r =0.300, P =0.006), DG (r =0.333, P =0.002) and CA4 (r =0.323, P =0.003). Conclusions Patients with WMH showed an asymmetric atrophy pattern of hippocampal subregions, mainly in the right hippocampus. The right molecular layer, DG, and CA4 influenced executive function in WMH patients, while the right subiculum atrophy affected general cognitive and language function.

Key words: White matter hyperintensity; Hippocampal; Hippocampal subregion; Cognitive Impairment; Executive dysfunction

摘要： 目的 探讨脑白质高信号（white matter hyperintensity，WMH）患者海马亚区的萎缩情况及其与认知 功能障碍的相关性。 方法 前瞻性连续纳入南京鼓楼医院2017年1月-2019年12月收治的WMH患者，将同期门诊招募的健 康志愿者作为正常对照。所有受试者接受头颅MRI检查及认知功能检查，根据MMSE和MoCA评分将 WMH患者分成无认知障碍组及认知障碍组。利用FreeSurfer 6.0软件进行海马亚区的分割，计算双侧 海马尾、下托、CA1、海马裂、前下托、旁下托、分子层、齿状回、CA3、CA4、海马伞及海马杏仁核过渡区 的亚区体积，同时计算脑室周围、深部及总WMH体积。比较对照组、WMH认知障碍组和WMH无认知障 碍组之间总海马体积及各海马亚区体积的差异。在WMH患者中分析萎缩的海马亚区与WMH体积的相 关性，在WMH伴认知障碍组中分析海马亚区体积与各个认知域功能障碍的相关性。 结果 共纳入对照组85例，WMH无认知障碍组79例及WMH认知障碍患者89例。与对照组相比，WMH 无认知障碍组患者右侧齿状回（P =0.006）、CA3（P =0.006）和CA4（P =0.020）海马亚区出现萎缩，而 WMH认知功能障碍组则表现为右侧下托（P =0.022）、分子层（P =0.003）、齿状回（P =0.001）、CA3 （P =0.039）、CA4（P =0.003）及双侧海马伞亚区（左侧P =0.004，右侧P =0.020）体积降低。在WMH患者 中，右侧齿状回体积与总WMH体积（r =-0.134，P =0.035）及室周WMH体积（r =-0.128，P =0.045）呈负 相关，右侧CA3体积同样与总WMH（r =-0.149，P =0.020）及室周WMH（r =-0.139，P =0.029）呈负相关。 此外，在WMH伴认知障碍组中，总体认知功能（r =0.315，P =0.004）及语言功能（r =0.318，P =0.006） 均与右侧下托体积呈正相关；执行功能则与右侧分子层（r =0.300，P =0.006）、齿状回（r =0.333， P =0.002）和CA4（r =0.323，P =0.003）的体积呈正相关。 结论 WMH患者表现为非对称性海马萎缩模式，以右侧海马萎缩为主。右侧分子层、齿状回及CA4区 亚区影响WMH患者执行功能而右侧下托的萎缩则影响总体认知和语言功能。

关键词: 脑白质高信号; 海马; 海马亚区; 认知功能; 执行功能障碍