Jakimovski Dejan, Zivadinov Robert, Weinstock Zachary, Fuchs Tom A, Bartnik Alexander, Dwyer Michael G, Bergsland Niels, Weinstock-Guttman Bianca, Benedict Ralph H B
Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High St., Buffalo, NY, 14203, USA.
Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA.
J Neurol. 2023 Nov;270(11):5223-5234. doi: 10.1007/s00415-023-11945-2. Epub 2023 Aug 27.
The structural changes associated with cognitive performance in older people with multiple sclerosis (PwMS; age ≥ 50 years old) remain unknown.
To determine the relationship between whole-brain (WBV), thalamus as the largest deep gray matter nuclei, and cortex-specific volume measurements with both cognitive impairment and numerical performance in older PwMS. The main hypothesis is that cognitive impairment (CI) in older PwMS is explained by cortical thinning in addition to global and thalamic neurodegenerative changes.
A total of 101 older PwMS underwent cognitive and neuroimaging assessment. Cognitive assessment included tests established as sensitive in MS samples (Minimal Assessment of Cognitive Function in MS; MACFIMS), as well as those tests often utilized in Alzheimer's dementia studies (Wechsler's Memory Scale, Boston Naming Test, Visual Motor Integration and language). Cognitive impairment (CI) was based on -1.5 standard deviations in at least 2 cognitive domains (executive function, learning and memory, spatial processing, processing speed and working memory and language) when compared to healthy controls. WBV and thalamic volume were calculated using SIENAX/FIRST and cortical thickness using FreeSurfer. Differences in cortical thickness between CI and cognitively preserved (CP) were determined using age, sex, education, depression and WBV-adjusted analysis of covariance (ANCOVA). The relationship between domain-specific cognitive performance and cortical thickness was analyzed by linear regression models adjusted for age, sex, education, depression, WBV and thalamic volume. Benjamini-Hochberg-adjusted p-values lower than 0.05 were considered significant.
The average age of the study population was 62.6 (5.9) years old. After adjustment, CI PwMS had significantly thinner left fusiform (p = 0.0003), left inferior (p = 0.0032), left transverse (p = 0.0013), and bilateral superior temporal gyri (p = 0.002 and p = 0.0011) when compared to CP PwMS. After adjusting for age, sex, education, depression WBV, and thalamic volume, CI status was additionally predicted by the thickness of the left fusiform (p = 0.001) and left cuneus gyri (p = 0.004). After the adjustment, SDMT scores were additionally associated with left fusiform gyrus (p < 0.001) whereas letter-based verbal fluency performance with left pars opercularis gyrus (p < 0.001).
In addition to global and thalamic neurodegenerative changes, the presence of CI in older PwMS is additionally explained by the thickness of multiple cortical regions.
多发性硬化症（PwMS；年龄≥50岁）老年人认知功能相关的结构变化尚不清楚。
确定全脑体积（WBV）、作为最大深部灰质核团的丘脑以及特定皮层体积测量值与老年PwMS患者的认知障碍和数字表现之间的关系。主要假设是，老年PwMS患者的认知障碍（CI）除了由整体和丘脑神经退行性变化外，还可由皮层变薄来解释。
共有101名老年PwMS患者接受了认知和神经影像学评估。认知评估包括在MS样本中已确定为敏感的测试（MS认知功能最小评估；MACFIMS），以及那些在阿尔茨海默病痴呆研究中常用的测试（韦氏记忆量表、波士顿命名测试、视觉运动整合和语言）。与健康对照相比，认知障碍（CI）基于至少2个认知领域（执行功能、学习和记忆、空间处理、处理速度、工作记忆和语言）中-1.5个标准差。使用SIENAX/FIRST计算WBV和丘脑体积，使用FreeSurfer计算皮层厚度。使用年龄、性别、教育程度、抑郁和WBV调整的协方差分析（ANCOVA）确定CI组和认知保留（CP）组之间皮层厚度的差异。通过对年龄、性别、教育程度、抑郁、WBV和丘脑体积进行调整的线性回归模型分析特定领域认知表现与皮层厚度之间的关系。Benjamini-Hochberg调整后的p值低于0.05被认为具有统计学意义。
研究人群的平均年龄为62.6（5.9）岁。调整后，与CP PwMS相比，CI PwMS患者的左侧梭状回（p = 0.0003）、左侧颞下回（p = 0.0032）、左侧颞横回（p = 0.0013）和双侧颞上回（p = 0.002和p = 0.0011）明显更薄。在调整年龄、性别、教育程度、抑郁、WBV和丘脑体积后，CI状态还可由左侧梭状回（p = 0.001）和左侧楔叶回（p = 0.004）的厚度预测。调整后，符号数字模式测试（SDMT）分数还与左侧梭状回（p < 0.001）相关，而基于字母的语言流畅性表现与左侧岛盖部回（p < 0.001）相关。
除了整体和丘脑神经退行性变化外，老年PwMS患者CI的存在还可由多个皮层区域的厚度来解释。
