Chronic traumatic encephalopathy: predictors of the development of cognitive disorders and functional disability

K. Duve, S. Shkrobot, Z. Salii
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Abstract

Background. Predicting the individual risk of developing cognitive impairment and functional disability in everyday life among patients with chronic traumatic encephalopathy (CTE) will allow timely and adequate treatment to prevent dementia. Therefore, the study aimed to develop a mathematical model for predicting the risk of cognitive disorders and functional disability in patients with CTE based on the analysis of polymorphic variants of the ACE, AT2R1, eNOS, ePON1, IL-1β, IL-10, TNF-α genes, as well as cofactors (gender, age group, follow-up, presence/absence of somatic comorbidity). Materials and methods. We examined 145 individuals with CTE who were undergoing inpatient treatment in the Communal Non-Profit Enterprise “Ternopil Regional Clinical Psychoneurological Hospital” in 2021–2022 and were included in the retrospective analysis. The molecular and genetic testing was performed for 26 patients. The molecular and genetic differentiation of the studied polymorphic variants of genes was carried out in the molecular and genetic laboratory of the State Institution “Reference Centre for Molecular Diagnostics of the Ministry of Health of Ukraine” in Kyiv. Cognitive functions were studied using the Montreal Cognitive Assessment (MoCA), activities of daily living — with the Barthel index. Statistical analysis was done using Microsoft Excel and Statistica 13.0 computer software. A logistic regression analysis was performed to determine the likelihood of cognitive impairment and functional disability in patients with CTE. Results. When analyzing polymorphic variants of the ACE, AT2R1, eNOS, ePON1, IL-1β, IL-10, TNF-α genes, as well as such cofactors as gender, age group, follow-up, presence/absence of somatic comorbidity in the context of the development of cognitive disorders in patients with CTE, it has been found that the I/D polymorphism of the ACE gene has the most significant prognostic value (in the presence of the D/D genotype, the probability of cognitive impairment is 83.33 %). At the same time, patients with CTE who were carriers of the D allele of the ACE gene had a significant decrease in the MoCA score compared to the group of those who didn’t carry this allele. Regarding the development of functional disability in patients with CTE, the C108T polymorphism of the PON1 gene has the most significant prognostic value (in the presence of the T/T genotype, the risk of functional disability is 41.49 %, with significantly lower Barthel index compared to the C/C homozygotes). Conclusions. It was found that the I/D polymorphism of the ACE gene and the C108T polymorphism of the PON1 gene are likely associated with the development of cognitive impairment and functional disability in patients with CTE that indicates the feasibility of further studies involving a larger sample of patients.
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慢性创伤性脑病:认知障碍和功能障碍发展的预测因素
背景。预测慢性创伤性脑病(CTE)患者在日常生活中出现认知障碍和功能障碍的个体风险,将有助于及时、充分地治疗,预防痴呆症的发生。因此,本研究旨在根据对 ACE、AT2R1、eNOS、ePON1、IL-1β、IL-10、TNF-α 基因多态性变异的分析,以及辅助因素(性别、年龄组、随访、有无躯体合并症)的分析,建立预测 CTE 患者认知障碍和功能障碍风险的数学模型。材料与方法我们对 2021-2022 年期间在 "捷尔诺波尔地区临床精神神经病医院 "接受住院治疗并被纳入回顾性分析的 145 名 CTE 患者进行了研究。对 26 名患者进行了分子和基因检测。所研究基因多态性变体的分子和基因分化在基辅国家机构 "乌克兰卫生部分子诊断参考中心 "的分子和基因实验室进行。认知功能使用蒙特利尔认知评估(MoCA)进行研究,日常生活活动使用巴特尔指数进行研究。统计分析使用 Microsoft Excel 和 Statistica 13.0 计算机软件进行。为确定 CTE 患者出现认知障碍和功能障碍的可能性,进行了逻辑回归分析。结果。在分析 ACE、AT2R1、eNOS、ePON1、IL-1β、IL-10、TNF-α 基因的多态性变异,以及性别、年龄组、随访、有无躯体合并症等辅助因素与 CTE 患者认知障碍发展的关系时,发现 ACE 基因的 I/D 多态性具有最重要的预后价值(存在 D/D 基因型时,认知障碍的概率为 83.33 %).同时,ACE基因D等位基因携带者的CTE患者的MoCA评分与不携带该等位基因的患者相比明显下降。关于 CTE 患者出现功能障碍的情况,PON1 基因的 C108T 多态性具有最重要的预后价值(出现 T/T 基因型时,出现功能障碍的风险为 41.49%,与 C/C 同型基因携带者相比,Barthel 指数明显降低)。结论研究发现,ACE基因的I/D多态性和PON1基因的C108T多态性很可能与CTE患者认知障碍和功能障碍的发展有关,这表明进一步开展涉及更多患者样本的研究是可行的。
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