【作者】 杨月嫦；

【导师】 谢瑞满； 罗蔓； 邱东鹰； 刘剑英；

【作者基本信息】 复旦大学 ， 老年医学， 2009， 硕士

【摘要】 目的:1、研究60岁及以上2型糖尿病老年患者的不同程度认知功能损害发生率,分析其相关影响因素;2、研究60岁及以上非卒中的2型糖尿病老年患者12周内认知功能状态的变化情况,分析其影响因素。资料与方法:评价指标及标准:运用MMSE、LOTCA、CDR、GDS量表评价总体认知功能,并根据MMSE、LOTCA和CDR量表中的子项目检查内容分别评价定向力、语言、记忆力、注意力、视觉空间能力和执行功能等不同领域的认知功能。认知功能损害的分组主要根据总体认知功能损害水平进行划分。正常认知功能组:MMSE总分≥24分,CDR总分为0,GDS分级为1级,三项同时成立;轻度认知功能损害组:MMSE总分≥24分,CDR总分为0.5或GDS分级为2、3级,两者同时成立;重度认知功能损害组:MMSE总分＜24分,CDR总分≥1,GDS分级≥14级,三者有一项满足即成立。糖尿病的血糖水平根据餐前、餐后2小时静脉血浆葡萄糖值及糖化血红蛋白评价血糖水平,其中糖化血红蛋白测定水平评价过去8～12周平均血糖水平。平均血糖控制情况的分组主要根据糖化血红蛋白的水平进行划分。血糖控制良好组:HbAlc＜6.5%;血糖控制一般组:HbAlc:6.5%～7.5%;血糖控制不良组:HbAlc＞7.5%。研究内容:第一部分:采用横断面研究方法。根据认知功能损害的分组标准,将60岁及以上的2型糖尿病老年患者划分3组:正常认知功能组、轻度认知功能损害组和重度认知功能损害组。分别进行三组间和两组间(正常认知功能损害组和轻度认知功能损害组、轻度认知功能损害组和重度认知功能损害组)的认知功能的比较。影响2型糖尿病老年患者认知功能损害的各项相关因素,包括基本人口学特征、血管危险因素、糖尿病各项指标等因素,进行单因素方差分析,观察三组间各项因素的差异,有统计学意义的因素再运用Bonferroni法进行两组间比较。运用多分类有序反应变量Logistic回归模型,对单因素比较中有差异的因素进行多因素分析,校正因素间相互作用,找出影响三组患者的认知功能损害的相关因素。第二部分:采用前瞻性队列研究方法。以第一部分的横断面调查为基线,对60岁及以上非卒中的2型糖尿病老年患者随访12周,12周后进行认知功能的评价和糖化血红蛋白测定,运用配对t检验,比较基线和12周后的认知功能、平均血糖水平的变化。对12周后有认知功能下降的指标进行相关危险因素分析:运用单因素Logistic回归法分析单一的危险因素;多因素Logistic逐步回归法进行主要危险因素的分析;运用多因素Logistic回归法,校正年龄混杂因素,分析糖尿病各项指标对下降的认知功能的影响;对血糖平均控制情况进行分层,分为良好、一般和不良三层,运用多因素Logistic回归法,分析在不同层面的血糖平均控制情况下,校正年龄混杂因素后,糖尿病各项指标与认知功能下降的相关性;对糖尿病微血管病变的三大病变部位,分别是糖尿病肾病、糖尿病周围神经病变、糖尿病视网膜病变,运用多因素Logistic回归法分析各病变部位与认知功能下降的相关性。结果:第一部分:共计214例入选本研究,其中正常认知功能组76例(35.5%),轻度认知功能损害组92例(43.0%),重度认知功能损害组46例(21.5%)。总体认知功能和不同领域认知功能进行三组间比较,均有统计学差异(P＜0.01)。两组间比较:其中正常认知功能组和轻度认知功能损害组的比较,除MMSE、CDR、定向力、语言功能评价指标无差异外,其余均达到统计学差异(P＜0.01);轻度认知功能损害组和重度认知功能损害组的比较,总体认知功能和不同领域认知功能均有统计学差异(P＜0.01)。三组间各项影响因素进行比较,其中年龄、受教育程度、糖尿病病程、糖尿病微血管病变(糖尿病视网膜病变)、低血糖反应、卒中和苯二氮卓类催眠药治疗有统计学差异(P＜0.05);两组间比较,正常认知功能组和轻度认知功能损害组之间存在年龄、卒中、糖尿病病程、低血糖反应和苯二氮卓类催眠药治疗的统计学差异(P＜0.0167);轻度认知功能损害组和重度认知功能损害组之间存在受教育程度、卒中、糖尿病微血管病变(糖尿病视网膜病变)的统计学差异(P＜0.0167)。三组间单因素分析中有统计学差异的相关影响因素,进行多因素分析后,显示不同程度认知功能损害的发生与年龄(OR=1.166,95%CI:1.101～1.234)和卒中(OR=17.668,95%CI:2.097～148.829)有关。第二部分:基线时共182例60岁及以上非卒中2型糖尿病老年患者,12周后共178例完成随访,失访4例(失访率2.20%)。基线和12周后的各项认知功能指标、糖化血红蛋白进行前后比较,其中LOTCA总分、记忆力、视觉空间能力提示下降(P＜0.01),糖化血红蛋白无统计学差异。下降的认知功能运用单因素Logistic回归法分析危险因素,结果显示LOTCA总分下降与年龄、受教育程度、性别、微血管病变、糖尿病病程、睡眠状态及苯二氮卓类催眠药治疗有关;记忆力下降与年龄、受教育程度、职业、低血糖反应有关;视觉空间能力下降与年龄、性别、受教育程度、职业、微血管病变、糖尿病病程、基线时和12周后糖化血红蛋白水平有关。多因素Logistic逐步回归法分析影响各项认知功能下降的主要危险因素,结果提示LOTCA总分下降主要与年龄(OR=1.066,95%CI:1.016～1.119)、受教育程度(OR=0.236,95%CI:0.103～0.538)和微血管病变(OR=2.859,95%CI:1.141～7.167)有关;记忆力下降主要与年龄(OR=1.076,95%CI:1.023～1.132)、低血糖反应(OR=10.570,95%CI:3.199～34.925)、职业(OR=0.793,95%CI:0.678～0.927)有关;视觉空间能力下降主要与受教育程度(OR=0.120,95%CI:0.097～0.414)和12周后的糖化血红蛋白水平(OR=1.552,95%CI:1.130～2.132)有关。校正年龄因素,糖尿病各项指标中,其中微血管病变(OR=2.919,95%CI:1.096～7.773)与LOTCA总分下降相关,低血糖反应(OR=8.679,95%CI:2.642～28.504)与记忆力下降相关,12周后的糖化血红蛋白水平(OR=1.485,95%CI:1.021～2.159)、微血管病变(OR=2.626,95%CI:1.013～6.808)与视觉空间能力下降有关。对12周内的平均血糖控制情况和糖尿病不同部位的微血管病变进行分层分析,提示血糖控制良好组患者的视觉空间能力下降与微血管病变有关,血糖控制一般组患者的视觉空间能力下降与糖尿病各项指标关系不大,血糖控制不良组患者的视觉空间能力下降与胰岛素治疗有关;糖尿病各部位的微血管病变中仅视网膜病变与视觉空间下降有关。结论:60岁及以上2型糖尿病老年患者出现不同程度、不同领域认知功能损害的比例较大。导致认知功能损害因素是多方面的,其中与年龄、卒中相关性较明显。60岁及以上非卒中的2型糖尿病老年患者12周后可出现总体认知功能、记忆力和视觉空间能力下降。在无卒中因素作用下,短期内认知功能下降与人口学因素和糖尿病各项指标均有关,其中与糖尿病各项指标相关性加强。该研究为2型糖尿病老年患者的认知功能损害的预防措施提供一定临床依据。本项研究有助于认知功能研究领域的深入开展。更多还原

【Abstract】 Objective:To investigate the profiles of different degrees of cognitive function impairment, evaluate the associations between cognitive function deterioration and relative factors in elderly patients with type 2 diabetes aged 60 and over.To follow-up the development of cognitive function impairment and assess possible risk factors in these cases without stroke at the end of 12 weeks.Methods:All 214 cases with type 2 diabetes aged 60 and over were selected in the study. The basic medical history,test of glucose level,and cognitive function status assessed by the Mini-Mental State Examination(MMSE),Loeweistein Occupational Therapy Cognitive Assessment(LOTCA),Clinical Dementia Rating(CDR) and Global Deterioration Scale(GDS) were collected successfully.Cognitive function status was divided into three subgroups depending on the total scores of tests of MMSE,LOTCA and CDR.Three subgroups of cognitive function status were defined as normal cognitive function(NCF) with MMSE≥24,CDR=0 or GDS=1, mild cognitive impairment(MCI) with MMSE≥24,CDR=0.5 or GDS=2-3,and severe cognitive impairment(SCI) with MMSE＜24,CDR≥1 or GDS≥4.The scores of six domains from MMSE,LOTCA and CDR were recognized as the six cognitive function status of orientation,memory,language,visuospatial ablities, attention,executive function separately.The 178 cases of 182 patients without stroke were successfully followed-up to the end of 12 weeks,and the profiles of cognitive function and glycosylated hemoglobin Alc(HbAlc) were tested.Rusult:PartⅠ:Of the all 214 cases,76 cases(35.5%) with NCF,92 patients(43.0%) with MCI and 46 patients(21.5%) with SCI were found.Compare of total and domain scores of cognitive function within three subgroups were showed significantly differences(P＜0.01).And compare of total and domain scores of cognitive function between MCI and SCI were also showed significantly differences(P＜0.01).Compare of the scores of cognitive function but scores of MMSE,CDR and orientation,language between NCF and MCI were showed significantly differences(P＜0.01).The univariate analysis of age,education level,history of hypoglycemia and stroke,benzodiazepine use,duration of 2-diabetes and the diabetic microangiopathy within three subgroups were showed significantly differences(P＜0.05).Compare of education level,history of stroke,and the diabetic microangiopathy between MCI and SCI were showed significantly differences(P＜0.0167).And compare of age, history of stroke,benzodiazepine use,duration of 2-diabetes and history of hypoglycemia between NCF and MCI were showed significantly differences(P＜0.0167).The assosiations of the above significant factors within three subgroups were analyzed with Polytomous Ordinal Logistic Regression models. Age(OR=1.166,95%CI:1.101～1.234) and history of stroke(OR=17.668,95%CI: 2.097～148.829) were showed significantly differences after adjusting BMI and occupation.PartⅡ:The 178 patients without stroke were successfully followed-up at the baseline and the end of 12 weeks,and the profiles of cognitive function and HbAlc were tested.The scores of LOTCA,memory performance and visuospatial abilities but the HbAlc were showed significantly decline(P＜0.01) with paired t test.The univariate analysis of above relative factors was assessed.The decrease score of LOTCA was associated with age,education level,gender,diabetic retinopathy,duration of diabetes,and benzodiazepine use.The memory decline was associated with age,education level,occupation,and history of hypoglycemia.The decrease score of visualspatial function was associated with age,education level, gender,occupation,diabetic retinopathy,duration of diabetes,and history of hypoglycemia.The Stepwise Logistic Regression analysis was used to assess the risk factors of cognitive function impairement.The decrease score of LOTCA was associated with age(OR=1.066,95%CI:1.016～1.119),education level(OR=0.236,95%CI: 0.103～0.538) and diabetic retinopathy(OR=2.859,95%CI:1.141～7.167).The memory decline was associated with age(OR=1.076,95%CI:1.023～1.132),history of hypoglycemia(OR=10.570,95%CI:3.199～34.925) and occupation(OR=0.793, 95%CI:0.678～0.927).The decrease score of visualspatial function was associated with education level(OR=0.120,95%CI:0.097～0.414) and HbAlc level at the end of 12 weeks(OR=1.552,95%CI:1.130～2.132).Of the factors in diabetes,the decrease score of LOTCA was associated with diabetic retinopathy(OR=2.919,95%CI:1.096～7.773),the memory decline was associated with history of hypoglycemia(OR=8.679,95%CI:2.642～28.504),and the decrease score of visualspatial function was associated with diabetic retinopathy(OR=2.626,95%CI:1.013～6.808) and HbAlc level at the the end of 12 weeks(OR=1.485,95%CI:1.021～2.159) after adjusting age.The factors of average blood glycemic level and subtype of diabetic microangiopathy was also statistically analysed.The decrease score of visualspatial function was associated with diabetic microangiopathy in the subgroup of well-controlled blood glycemic level.The decrease score of visualspatial function was not associated with the all factors of diabetic in the subgroup of controlled blood glycemic level.The decrease score of visualspatial function was associated with insulin treatment in the subgroup of uncontrolled blood glycemic level.The decrease score of visualspatial function was only associated with diabetic retinopathy in the all subtype of diabetic microangiopathy.Conclusion:The cognitive function impairment in the elderly patients with type 2 diabetes was prevalence and associated with multiple risk factors in which the age and stroke were important.The impairment of total cognitive function,memory and visualspatial function were showed at the end of 12 weeks in elderly patients without storke of type 2 diabetes aged 60 and over.The cognitive function decline was obviously associated with the factors of diabetes in above cases.The results were helpful to prevent and treat the cognitive function impairment in the elderly patients with type 2 diabetes.The methods of the study would be benefit in the field of cognitive function in the future.更多还原