阿尔茨海默病患者证候演变规律及fNIRS脑血流动力学特征研究

Study on the Evolution Principles of Traditional Chinese Medicine syndromes and fNIRS Cerebral Hemody⁃namic Characteristics in Patients with Alzheimer's Disease

目的探讨阿尔茨海默病(AD)发展过程中各阶段患者证候虚、痰、瘀的变化规律和功能性近红外光谱(fNIRS)脑血流动力学特征。方法共纳入主诉记忆减退患者497例,分为主观认知下降(SCD)组198例、轻度认知障碍(MCI)组228例和AD组71例。采集患者的一般资料及神经心理学评价结果,进行中医证候调查,采集大脑前额叶fNIRS数据。描述统计分析各组患者的中医证候分布情况,比较各组中医证候积分,采用Logistic回归分析中医证候对患者的影响,采用Apriori算法进行证候间的关联规则分析,并分析各组患者的大脑前额叶fNIRS血流动力学特征。结果肾精亏虚证是AD各阶段最主要的证候,各组间患者的肾精亏虚、痰浊阻窍、瘀血阻络、气血亏虚、热毒内盛、腑滞浊留证分布差异均具有统计学意义(P<0.01),且各组间的肾精亏虚证候积分差异有统计学意义(P<0.01)。Logistic回归分析发现,肾精亏虚、气血亏虚证是SCD组的主要危险因素(P<0.05);痰浊阻窍证是MCI组的主要危险因素(P<0.05);热毒内盛、腑滞浊留证是AD组的主要危险因素(P<0.05)。关联规则分析发现,SCD组以肾精亏虚+痰浊阻窍组合支持度(33.33%)最高,MCI组和AD组均以肾精亏虚+瘀血阻络组合支持度(32.90%和52.13%)最高。前额叶fNIRS结果表明,各组间患者的平均ΔHbO_(2)浓度在左前额叶背外侧区依次下降(P<0.05),且各组间左前额叶背外侧区平均ΔHbO_(2)浓度与MoCA分数呈负相关(r=-0.142,P<0.05)。进一步分析发现,各组间患者肾精亏虚证的左前额叶背外侧区平均ΔHbO_(2)浓度差异具有统计学意义(P<0.05)。结论肾虚是AD发病的基础,关键损伤脑区为左前额叶背外侧皮层,痰、瘀等浊邪是疾病加重的病理因素,其证候呈现“肾虚→痰浊→血瘀→浊毒”的虚实演变规律,基于fNIRS检测的前额叶血流动力学变化与证候变化特点相一致,可用于AD患者认知损伤的程度评估。

Objective To explore the evolution principles of symptoms including deficiency,phlegm and blood stasis,and of the functional near-infrared spectroscopy(fNIRS)cerebral hemodynamic characteristics at various stages in patients of Alzheimer's disease.Methods A total of 497 patients with complaint of memory loss were included,and were divided into subjective cognitive decline(SCD)group(198 participants),mild cognitive impairment(MCI)group(228 participants)and dementia(AD)group(71 participants).Neuropsychological evaluation,traditional Chinese medicine(TCM)syndrome investigation,and fNIRS data collection of prefrontal cortex were performed in each group.Descriptive statistics were used to analyze the distribution of TCM syndromes and the difference of TCM syndrome scores in each group;logistic regression was used to analyze the influence of TCM syndromes on the inci⁃dence of the patients;association rules were used to analyze the TCM syndromes of the patients;the hemodynamic characteristics of fNIRS in the prefrontal cortex of each group were compared.Results Kidney essence deficiency syndrome was the dominant syndrome in all stages of AD.There were statistically significant differences in the distribu⁃tion frequency of kidney essence deficiency,phlegm turbidity obstructing orifices,blood stasis obstructing collaterals,qi and blood deficiency,heat toxin in the interior,and fu-organ stagnation and turbidity retention syndromes among the three groups(P<0.01),and the scores of kidney essence deficiency syndrome among the three groups were statistically significant(P<0.01).Logistic regression analysis showed that kidney essence deficiency,and qi and blood deficien⁃cy syndromes were the main risk factors for the SCD group(P<0.05),phlegm turbidity obstructing orifices syn⁃drome was the main risk factor for the MCI group(P<0.05),and heat toxin in the interior,and fu-organ stagnation and turbidity retention syndromes were the main risk factors for the AD group(P<0.05).The association rule analy⁃sis showed that the combination of kidney essence deficiency plus phlegm turbidity obstructing orifices had the highest support(33.33%)in the SCD group,and the combination of kidney essence deficiency plus blood stasis obstructing collaterals had the highest support(32.90%and 52.13%)in both the MCI and AD group.The prefrontal fNIRS re⁃sults showed that the meanΔHbO_(2)concentration in the left dorsolateral prefrontal cortex(LDLPFC)decreased sequen⁃tially among the three groups(P<0.05),and the meanΔHbO_(2)concentration in the LDLPFC was negatively correlated with the MoCA score among the three groups(r=-0.142,P<0.05).Further analysis showed that the meanΔHbO_(2)concentration in the LDLPFC of patients with kidney essence deficiency syndrome were statistically significant differ⁃ences among the three groups(P<0.05).Conclusion Kidney deficiency is the basis of the pathogenesis of AD,and the key brain area damaged is the LDLPFC.Turbid pathogens such as phlegm and blood stasis are the pathological factors that aggravate the disease,and the syndromes of AD show the evolution law of deficiency and excess as“kidney deficiency→phlegm turbidity→blood stasis→turbid toxin”.The changes in prefrontal hemodynamics based on fNIRS are consistent with the changes in the characteristics of symptoms,which can be used to assess the degree of cognitive impairment in AD patients.