Quantitative EEG and perfusional single photon emission computed tomography correlation during long-term donepezil therapy in Alzheimer's disease.

OBJECTIVE: There is an increasing interest in the effects of the acetylcholinesterase inhibitors (AChEIs) in Alzheimer's disease (AD), as investigated by means of objective, neurophysiological tools. In an open-label study, we evaluated the neurophysiological effects of chronic administration of donepezil to AD patients, by means of a correlative approach between quantitative EEG (qEEG) and perfusional brain single photon emission computed tomography (SPECT). METHODS: Sixteen patients (mean age: 74.8+/-7.9 years) with mild to moderate AD (MMSE score >13, mean: 20.7+/-4.6) underwent qEEG and SPECT examinations at the time of diagnosis (t0) and after approximately 1 year of donepezil therapy (t1). The brain SPECT (99mTc-hexamethylpropyleneamine oxime) was performed by means of a high-resolution SPECT camera; the qEEG was recorded from 19 scalp electrodes by average reference and digitized at 512 Hz. The mean frequency (MF) value of the mean power spectrum (fast Fourier transform) from 4 brain regions (one frontal and one temporal-parietal in each hemisphere) was chosen for statistical analysis. Changes in MMSE score and qEEG-MF values between t0 and t1 were assessed by analysis of variance. SPECT differences between t0 and t1, as well as the relationships between SPECT and qEEG changes, were assessed by statistical parametric mapping (SPM 99; height threshold: P=0.001 at cluster level). RESULTS: Between t0 and t1, the MMSE score significantly (P<0.05) decreased (from 20.7+/-4.64 to 19.1+/-5.09; 95% confidence interval: 1.14) and qEEG was unchanged. There was no regional perfusion decrease; a small area of relative perfusion increase was observed, including the right occipital cuneus and the left lingual gyrus. A positive correlation was found between the right frontal MF and brain perfusion in the left superior parietal lobule. A post hoc SPM analysis (height threshold: P=0.01) showed a positive correlation between brain perfusion and each of the 4 qEEG MF values in the left parietal lobe, including the precuneus, the superior parietal lobule, and the post-central gyrus. CONCLUSIONS: The posterior parietal region, which is involved in memory and attention, is often affected by hypoperfusion in AD, as a likely consequence of disconnection from the atrophic mesial temporal cortex. Metabolic activation induced by AChEIs may especially influence this disconnected but still not grossly impaired area, which could be one of the pathophysiological substrates of the cognitive effects of AChEIs. The modest topographical sensitivity of qEEG, reflecting the rather diffuse changes in AD, is further confirmed.     

The efficacy of galantamine in the treatment of Alzheimer's disease: comparison of patients previously treated with acetylcholinesterase inhibitors to patients with no prior exposure

BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) can provide benefits at the cognitive, behavioral, and functional levels to patients with Alzheimer's disease (AD). With more AChEIs now available, treatment considerations may include whether the patient has had prior exposure to an AChEI. OBJECTIVE: To compare the effects of galantamine in patients with AD who were previously exposed to AChEIs with its effects in patients with AD who had no previous exposure, using a post hoc analysis. RESULTS: Patients in groups treated with galantamine 16 mg/day and 24 mg/day achieved statistically significant improvements in ADAS-cog/11 scores in comparison with those who received placebo (naive: p = 0.003 and 0.005, respectively; prior exposure: p < 0.001 and 0.001, respectively). Similarly, a greater number of patients treated with galantamine 16 mg/day and 24 mg/day exhibited no change or improvement in their CIBIC-plus scores compared to patients who received placebo (naive: p < 0.001 and p = 0.077, respectively; prior exposure: p = 0.005 and p = 0.001, respectively). There were no significant differences in adverse events between naive patients and those with prior exposure to AChEIs. CONCLUSIONS: Galantamine is effective and safe in patients with AD, regardless of previous exposure to AChEIs.     

Differential efficacy of treatment with acetylcholinesterase inhibitors in patients with mild and moderate Alzheimer's disease over a 6-month period

There are various anticholinesterase inhibitors (AChEIs) for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). All AChEIs have shown greater efficacy than placebo in randomized, double-blind, parallel-group clinical trials. No differential studies have yet been made of the efficacy between all AChEIs. The study aims to determine the differential efficacy of the AChEIs with respect to a historical sample of patients with AD that were not treated with AChEIs. An open-label, prospective, observational study with a retrospective control group was undertaken to examine the evolution of the cognitive function over a 6-month period. The patients were assessed with the Mini-Mental State Examination (MMSE) at study entry and at 6 months. A general linear model was applied for repeated measurements with the MMSE score as the dependent variable, treatment type as an independent variable and the severity of the deterioration, age and the MMSE baseline score as covariables. Of the sample of 147 patients, 40 initiated treatment with donepezil, 32 with galantamine, 30 with rivastigmine and 45 were part of a historical sample of the memory clinic patients between 1991 and 1996 that had not been treated with AChEIs. The average age was 73.7 years (SD = 6.9; range = 52-86), 67.3% were women, 78.2% of the cases were mild and the MMSE baseline score was 18.1 points (range = 11-27). No significant intergroup differences were observed in these variables. The average doses of donepezil, galantamine and rivastigmine were 5.87 mg/day (SD = 1.92), 14.81 mg/day (SD = 6.25) and 6.41 mg/day (SD = 1.82), respectively. At 6 months, the difference in the MMSE score with respect to the untreated group was 1.6 points for donepezil (95% CI 0.79-2.37; p < 0.001), 0.99 points for galantamine (95% CI 0.14-1.85; p = 0.01) and 0.90 points for rivastigmine (95% CI 0.05-1.74; p = 0.03). No significant differences were observed in the efficacy among the groups treated with AChEIs (p > 0.05). Treatment with AChEIs significantly delays the global cognitive impairment associated with AD for at least 6 months. Our study found no significant differences in efficacy between donepezil, galantamine and rivastigmine. Further studies in the context of daily clinical practice will determine the clinical significance of the changes observed. An important variability of the response to the treatment was observed in treated patients.     

Laterality, region, and type of motor dysfunction correlate with cognitive impairment in Parkinson's disease.

We studied the relationship between two screening cognitive measures and off motor Unified Parkinson's Disease Rating Scale (UPDRS) scores in 108 Parkinson's disease patients. Multiple regressions were conducted to examine the UPDRS subscores' unique contributions to cognitive function. When including bradykinesia, rigidity, and postural/gait instability subscores, only bradykinesia predicted Mini Mental Status Examination (MMSE), normalized beta = -0.57, t(104) = -3.31, P < 0.01, and Dementia Rating Scale-2 (DRS-2), normalized beta = -0.45, t(104) = -2.55, P < 0.05. Tremor was not included in the regression analyses because it did not correlate with cognitive function. When including axial and appendicular subscores, only the axial subscore predicted MMSE, normalized beta = -0.39, t(105) = -3.19, P < 0.01, and DRS-2 scores, normalized beta = -0.40, t(106) = -3.28, P < 0.01. When including left-sided and right-sided subscores, only the right-sided symptoms predicted DRS-2 scores, normalized beta = -0.28, t(105) = -2.45, P < 0.05, and showed a trend toward predicting MMSE scores, normalized beta = -0.22, t(105) = -1.95, P = 0.054. We therefore found that right-sided symptoms (for laterality), axial symptoms (for region), and bradykinesia (for type of symptoms) were the best predictors of cognitive function.     

Predictors of depressive symptoms among spouse caregivers in Parkinson's disease.

The objective of this work was to determine the predictors of depressive symptoms among spouse caregivers of Parkinson's disease (PD) patients. Little is known about the strain in giving care to PD patients and how the motor, cognitive, and behavioral complications of PD contribute to depression among spouse caregivers. Forty-five consecutive PD patients and their spouse caregivers agreed to be evaluated after a routine clinic visit. Patient demographic data and the presence of hallucinations, delusions, incontinence, and sleep disturbances were obtained. The patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS-motor section), Hoehn and Yahr (H&Y) staging, and the Mini-Mental State Examination (MMSE). Depressive symptoms were assessed using the 17-item Hamilton Depression Scale (HAMD-17) and the Beck Depression Inventory-II (BDI-II) on patients and spouses. Thirty men and 15 women had a mean age of 71.5 years (range 53-85), average PD duration of 10 years (range 1-26), a mean "on" H&Y stage of 2.8 and an MMSE mean score of 26 (range 13-30). There was good correlation between the HAMD-17 and the BDI-II scores in both patients (r = 0.69, P = 0.001) and spouses (r = 0.66, P < 0.001). A moderate correlation was noted between the spouse HAMD-17 score and the patient UPDRS-motor score (r = 0.34; P = 0.02), the age of PD onset (r = 0.33; P = 0.02) and patient HAMD-17 scores (r= 0.29; P = 0.05). A stronger correlation was noted between spouse HAMD-17 scores and the years of PD duration (r= 0.43; P = 0.003). There was a significant difference in the mean spouse HAMD-17 scores among PD patients with sleep disturbances versus those who did not (10.2 vs. 6.4; P = 0.04). However, on stepwise regression analysis, only the duration of PD remained significant (adjusted r = 0.17; P = 0.003). No difference was noted with hallucinations, delusions or incontinence. We concluded that the duration of PD appears to be the strongest predictor of depressive symptoms among spouse-caregivers in this small cohort.     

强迫症团体认知行为治疗与药物治疗的随机对照研究

目的分析团体认知行为治疗(group cognitive-behavioral therapy,GCBT)对强迫症患者的疗效。方法本研究采用随机对照试验设计,与常规抗强迫药物治疗做对照。将符合入组标准的94例未用药强迫症患者,采用Excel软件中的RAND函数产生随机数字表形成随机分组序列的简单随机分组法,随机分为GCBT组(47例)和药物治疗组(47例)。经12周的结构化GCBT治疗和常规抗强迫药物治疗,采用t检验、卡方检验和方差分析比较2组间Y-BOCS、HAMA14和HAMD24平均减分率和减分值的差异。结果(1)2组基线Y-BOCS及HAMA14评分差异无统计学意义(t=0.281,P=0.779;t=0.795,P=0.429),但GCBT组HAMD24评分显著低于药物治疗组(t=2.316,P<0.05)。2组各有16例患者退出治疗,总脱落率为34%(32/94)。(2)12周治疗结束时,2组患者的Y-BOCS评分较基线显著降低,GCBT组和药物治疗组治疗前后Y-BOCS平均减分率[(37.0±27.4)%比(45.5±22.9)%]和平均减分值[(9.0±6.3)分比(11.0±5.8)分]比较差异无统计学意义[F(1,62)=0.069,P=0.794;F(1,62)=0.001,P=0.975]。GCBT组和药物治疗组的有效率和治愈率差异无统计学意义(χ^2=1.653,P=0.199;χ^2=0.088,P=0.767)。(3)GCBT组HAMA14减分率和减分值与药物治疗组治疗前后比较差异无统计学意义(t=-0.922,P=0.362;t=1.082,P=0.286)。(4)GCBT组HAMD24减分率与药物治疗组治疗前后比较差异无统计学意义,但药物治疗组HAMD24减分值显著高于GCBT组(t=2.239,P=0.029)。结论GCBT与常规抗强迫药物治疗强迫症患者的强迫和焦虑症状的疗效相当,常规药物治疗对抑郁症状的疗效优于GCBT。     

阿尔茨海默病患者精神行为症状复发的影响因素

目的探讨影响阿尔茨海默病(AD)患者精神行为症状复发的相关因素。方法选取2008年3月至2011年9月在我院确诊为AD患者107例,采用神经精神量表(NPI)、病理行为评分表(BEHAVE-AD)、简易智力状态检查(MMSE)、日常生活活动能力量表(ADL)调查AD患者精神行为症状发作的特征,分析影响AD患者精神行为症状复发的因素。结果复发率为41.4%,居住环境改变(RR=4.96,95%CI:2.54～12.34,P<0.05),发作时NPI评分高(RR=1.26,95%CI:1.04～1.27,P<0.05),可增加AD患者BPSD的复发。结论发作时NPI评分、居住环境改变是AD患者BPSD复发的危险因素。     

艾斯能治疗阿尔茨海默病有效性及安全性的临床研究

目的　评价艾斯能治疗阿尔茨海默病 ( Alzheimer disease,AD)患者的有效性及安全性。方法　对 30例( MMSE≤ 2 6分 ) AD患者进行了多中心、开放、自身对照 1 6周临床试验 ,应用简易智能精神量表 ( MMSE)、AD评定量表 ( ADAS)及 Blessed-Roth痴呆量表判定疗效 ,检测患者生命体征及实验室指标 ,并进行安全性评价。结果　经艾斯能治疗 1 6周后 ,患者的认知功能 :MMSE较治疗前平均提高 3.9分 ,ADAS认知部分改善 5 .4分( P<0 .0 1 ,P<0 .0 5 ) ;患者的日常生活自理能力 :Blessed-Roth日常生活能力部分降低 1 .6分 ( P <0 .0 1 ) ;患者的精神行为异常 :ADAS的非认知行为部分减少 4 .2分 ,Blessed-Roth的人格部分降低 1 .4分 ( P<0 .0 5 ,P<0 .0 1 )。 5例 ( 1 6 % )出现轻度胆碱能兴奋性副作用。结论　艾斯能可改善 AD患者的认知功能、日常生活自理能力和精神行为异常 ,耐受性好 ,安全性高 ,其主要副作用为胆碱能兴奋性胃肠道反应     

Effects of donepezil on emotional/behavioral symptoms in Alzheimer's disease patients

BACKGROUND: This open-label study examined the effects of the reversible cholinesterase inhibitor donepezil on emotional/behavioral symptoms in Alzheimer's disease (AD) patients. METHOD: Patients were diagnosed as having probable/possible AD by National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria. This study used the CERAD Behavior Rating Scale for Dementia (CBRSD) and its subscales to evaluate a group of 25 AD patients treated with donepezil. Dosage was increased at 4 months for most patients from 5 to 10 mg q.h.s. Analysis of variance was used to compare scores over a period of 12 months. These patients were also compared, using t tests, to a reference group that had received no donepezil or other anticholinesterase. RESULTS: Donepezil administration was associated with improvement in Mini-Mental State Examination (MMSE) and CBRSD total scores at 3-month evaluation (p< or =.05). CBRSD depression and behavioral dysregulation scores improved transiently at 4 months (p< or =.05). MMSE, CBRSD total, CBRSD depression, and CBRSD behavioral dysregulation scores returned to baseline levels at 12 months, in contrast to the reference group, whose MMSE and CBRSD total scores worsened minimally over the 12 months. CONCLUSION: Donepezil has a mildly positive effect on emotional/behavioral symptoms in AD in addition to its effect on cognitive function.     

Effects of long-term Donepezil therapy on rCBF of Alzheimer's patients.

BACKGROUND: The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer's Disease (AD) has led to the need to assess the brain's response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period. METHODS: Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2+/-7.2; mean Mini-Mental State Examination score, MMSE: 19.8+/-3.5) underwent (t0) brain SPECT with 99mTc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t1) after 11+/-2.6 months of chronic Donepezil administration (5mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4+/-5.7, MMSE score: 20.6+/-3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13+/-1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings. RESULTS: The MMSE score declined significantly (P<0.01) from t0 to t1 both in untreated (from 20.6+/-3.5 to 17.8+/-4.4) and in treated (from 19.8+/-3.5 to 17.8+/-4.1) group. At t(0), the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t0 and t1, significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t1. By covariate SPM analysis between t0 and t1 in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region. CONCLUSIONS: Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients.     

Category verbal fluency predicted changes in behavioral and psychological symptoms of dementia in patients with Alzheimer's disease

Aim: Alzheimer's disease (AD) is characterized by cognitive symptoms and behavioral symptoms, and their association is inconsistent. The aim of this study was to investigate the relationship between cognitive function and the changes in behavioral and psychological symptoms of dementia (BPSD) in patients with AD. Methods: A total of 101 patients with probable AD were enrolled (57 women and 44 men, mean age 77.6 ± 7.7 years). The Category Verbal Fluency Test (CVFT), the Mini‐Mental State Examination (MMSE), the Constructional Praxis Test, the Delayed Word Recall Test, the Clinical Dementia Rating Scale, and the Neuropsychiatry Inventory (NPI) were administered at baseline. The NPI was reassessed with a median follow‐up duration of 10 months (range 6–18 months). The change in the NPI scores was defined as the end‐point score of the NPI minus the initial one. The associations between the changes in NPI total score, its four subdomains (hyperactivity, psychosis, affection, and apathy), and cognitive function were examined using multivariate linear models. The results were adjusted for confounders including demographics, baseline NPI, and duration of follow up. Results: The mean MMSE was 18.6 ± 5.6, the CVFT score was 7.1 ± 3.9, and the NPI score was 10.9 ± 13.8. Regression analyses found that the CVFT score (β = ?0.32, P = 0.004) was significantly associated with the change in NPI score, but not the MMSE, the Delayed Word Recall score, or the Constructional Praxis score. The CVFT score was significantly associated with changes in the psychosis subdomain (β = ?0.34, P = 0.001), but not the other subdomains. Conclusions: Our study showed that CVFT was predictive of the changes in behavior disturbance in patients with AD, particularly in the psychosis domain.     

业余活动与60岁以上老年人认知功能的关系

目的 探讨业余活动与60岁以上老年人认知功能的关系.方法 采用多阶段整群随机抽样方法调查石家庄市社区1203例60岁以上老年人,根据业余活动量分为高业余活动(n=504)和低业余活动(n=699)组,两组受试者性别、年龄和受教育年限相匹配,差异无统计学意义(P均＞0.05).采用简易智力状况检查(Mini-Mental State Examination,MMSE)和蒙特利尔认知评估(Montreal Cognitive Assessment,MoCA)评价两组受试者的认知功能状况.结果 (1)在1203例老年人中,MMSE筛查阳性率(低于划界值)19.5％(234例),MoCA筛查阳性率(低于划界值)66.9％(805例),MoCA的阳性检出率高于MMSE,差异有统计学意义(P=0.000);(2)按照MMSE和MoCA划界分,高业余活动组与低业余活动组MMSE筛查阳性率的差异无统计学意义(P=0.162),高业余活动组MoCA筛查阳性率高于低业余活动组,差异有统计学意义(P=0.012);(3)高业余活动组与低业余活动组的MMSE总分差异无统计学意义(P=0.061),高业余活动组MoCA总分高于低业余活动组,差异有统计学意义(P=0.011);(4)高业余活动组注意力和计算力、语言及延迟回忆得分高于低业余活动组,差异有统计学意义(P均＜ 0.05).结论 60岁以上高业余活动老年人认知功能损害发生率较低.     

A comparative study of behavioral and psychological symptoms of dementia in patients with Alzheimer's disease and vascular dementia referred to psychogeriatric services in Korea and the U.K

BACKGROUND: There is a paucity of cross-cultural studies of behavioral and psychological symptoms of dementia (BPSD). METHOD: BPSD were examined in consecutive series of referrals to a psychogeriatric service in Korea and the U.K. using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale and the Cornell Scale for Depression in Dementia (CSDD). Results were analyzed separately for Alzheimer's disease and vascular dementia. RESULTS: Koreans in both diagnostic groups had lower Mini-mental State Examination (MMSE) scores and higher BEHAVE-AD total and subscale scores for most subscales. In both countries, for both diagnostic groups, the total BEHAVE-AD score and several subscale scores were negatively correlated with the MMSE scores. Logistic regression analysis for Alzheimer's disease revealed that BEHAVE-AD total and most subscale scores independently predicted the country of origin in addition to the MMSE scores predicting the same. CONCLUSIONS: These differences in BPSD are most likely explained by the lower MMSE scores in the Korean sample. However, genuine differences in BPSD between the two countries can only be critically examined in a cross-cultural population-based epidemiological study for both diagnostic categories using validated instruments to measure BPSD and controlling for the influence of MMSE score.     

急性缺血性卒中患者胆碱能通路损伤与血管性认知障碍的相关性研究

目的 探索急性缺血性卒中患者胆碱能通路损伤与血管性认知障碍(VCI)的相关性.方法 连续收集在天津医科大学总医院神经内科住院的急性缺血性卒中患者87例.采用简易智能精神状态检查量表(MMSE)及蒙特利尔认知评估量表(MoCA)进行认知评估,同时使用脑胆碱能通路白质量表(CHIPS)和Fazekas量表进行脑白质病变测评,评价其对VCI的应用价值,并分析影像学评分与认知评估间的相关性.结果 以MMSE、MoCA作为界定认知障碍的标准时,缺血性卒中患者急性期认知障碍发生率分别为26.4％、79.3％,差异有统计学意义(P=0.000).CHIPS与MMSE、MoCA量表评分总分均呈负相关(r=-0.378,P=0.043;r =-0.504,P=0.005);Fazekas与MMSE及MoCA量表评分总分均无明显相关性(r=-0.094,P =0.627;r=-0.410,P =0.056);CHIPS评分与MoCA分项中视空间与执行功能、注意与抽象能力下降呈负相关,其中与视空间与执行功能下降关系最为密切(r=-0.514,P=0.004),而Fazekas评分仅与注意能力下降存在相关性(r=-0.404,P=0.030).结论 急性缺血性卒中患者胆碱能通路损伤与白质病变所致VCI相关;MoCA与CHIPS评分联合应用可以作为简便、快速筛查和评定白质病变所致VCI的良好工具.     

缺血性卒中慢性期睡眠质量下降发生率及相关危险因素的前瞻性队列研究

目的   调查缺血性卒中患者发病1年睡眠质量下降发生率及睡眠质量下降的危险因素。 方法  连续入组住院治疗的急性缺血性卒中患者。收集患者的人口学资料、既往病史、临床指标及影像学资料（急性期病灶部位）。随访患者发病后14?d是否存在卒中后抑郁、抗抑郁药物使用与否、评定美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale,NIHSS）、简易精神状态检查量表（Mini Mental State Examination,MMSE）、汉密尔顿抑郁量表（Hamilton Depression Rating Scale,HRSD）和汉密尔顿焦虑量表（Hamilton Anxiety Scale,HAMA）;发病1年后随访卒中复发、评定改良Rankin量表（modified Rankin Scale,mRS）、HRSD、HAMA和匹兹堡睡眠质量指数（Pittsburgh Sleep Quality Indexs,PSQI）。以PSQI≥8分为患者存在睡眠质量问题,对可能影响睡眠的因素进行单因素和多因素分析。 结果  研究期间共入组并完成随访的患者共233例。1年随访时PSQI≥8分,提示存在睡眠质量问题的患者为31例（13.3%）。单因素分析结果显示睡眠质量下降与随访时患者是否服用抗抑郁药物（χ2＝3.9657,P＝0.0464）、发病14?d内的HRSD评分（Z＝1.9712,0.0487）、1年随访时HRSD评分（Z＝6.7303,P<0.0001）和HAMA评分有关（Z＝6.6807,P<0.0001）;多因素分析显示1年随访阶段的HAMA评分［比值比（odds ratio,OR）1.666,95%可信区间（confidence interval,CI）1.309～2.120,P<0.0001］是卒中患者慢性期睡眠质量下降的独立危险因素。 结论  睡眠障碍在卒中慢性期发生率仍较高,慢性期焦虑水平是睡眠质量下降的独立危险因素。     

Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease.

Neuropsychiatric and behavioral symptoms are frequent and problematic components of Alzheimer's disease (AD). In two previously reported studies, metrifonate was shown to benefit behavioral symptoms as assessed by the Neuropsychiatric Inventory (NPI). In this post hoc analysis, detailed studies were completed to determine the effects of metrifonate on individual symptoms. This study was a retrospective analysis of pooled NPI data from two double-blind, placebo-controlled, multicenter 26-week studies of metrifonate that had achieved similar levels of cholinesterase inhibition. Mild-to-moderate probable AD patients received placebo (n = 222) or metrifonate (n = 450) 30 to 60 mg by weight or a 50-mg fixed dose once daily. At 26 weeks, metrifonate-treated patients had significantly reduced NPI total scores (P = .001) and fewer neuropsychiatric symptoms when compared with placebo-treated patients, including hallucinations (P = .004), agitation/aggression (P = .006), depression/dysphoria (P = .011), apathy (P = .019), and aberrant motor behavior (P = .008). Metrifonate reduced or stabilized neuropsychiatric disturbances in 60% of symptomatic patients. Almost 40% of metrifonate-treated patients had a clinically relevant reduction (> or = 30% decrease in NPI score) in their neuropsychiatric disturbances (P = .002). High proportions of metrifonate-treated patients manifested clinically relevant reductions in anxiety (58%, P = .009), apathy (51%, P = .020), and depression/dysphoria (50%, P = .021) compared to placebo. The metrifonate-associated reductions in NPI scores were evident by week 12 and were maintained for the 26-week study period. There was an overall effect size of metrifonate of approximately 15% on total NPI scores when compared to placebo. Metrifonate significantly reduced many of the psychiatric and behavioral symptoms of AD. The observations suggest that enhancement of cholinergic functions in AD has beneficial effects on behavior.     

叶酸、维生素B12和多奈哌齐治疗高同型半胱氨酸血症阿尔茨海默病患者的对照研究

目的:探讨叶酸、维生素B12和多奈哌齐联合应用对高同型半胱氨酸血症(HHcy)阿尔茨海默病(AD)患者的影响。方法:100例AD患者依就诊顺序随机分为3组:联合治疗组(叶酸、维生素B12和多奈哌齐联合治疗)34例、多奈哌齐治疗组(单用多奈哌齐)33例、对照组(仅常规治疗)33例,观察3个月。分别于治疗前和治疗3个月进行简易精神状态检查表(MMSE)、日常生活能力量表(ADL)评分及血清Hcy浓度检测。结果:治疗后,MMSE、ADL评分及血清Hcy浓度组间效应有统计学意义(F=29.71,F=6.06,F=6.62;P均0.01)。联合治疗组MMSE评分减分值、ADL评分减分值、血清Hcy浓度减分值均明显高于多奈哌齐治疗组(t=-3.48,t=-2.26,t=2.25;P均0.05或P0.01)及对照组(t=-9.14,t=-5.73,t=5.01;P均0.01)。治疗后Hcy浓度减分值与MMSE评分减分值、ADL评分减分值呈正相关(r=0.423,P0.01;r=0.240,P0.05)。结论:叶酸、维生素B12和多奈哌齐联合治疗可降低血清Hcy浓度,并改善AD患者的认知功能和行为能力。     

The effects of metrifonate on the cognitive, behavioral, and functional performance of Alzheimer's disease patients. Metrifonate Study Group.

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of metrifonate, a long-acting acetylcholinesterase inhibitor, in patients clinically diagnosed with probable Alzheimer's disease of mild-to-moderate severity. METHOD: This was a prospective, multicenter, 26-week, double-blind, parallel group study. The 264 randomized patients met diagnostic criteria of the National Institute of Neurological and Communicative Diseases and Stroke and the Alzheimer's Disease and Related Disorders Association for probable Alzheimer's disease. Patients had Mini-Mental State Examination (MMSE) scores of 10-26 and ischemic scores (Rosen modification) of <4. Metrifonate-treated patients received a single 50-mg dose once daily. The efficacy of metrifonate was investigated with respect to 3 symptom domains. Cognitive performance was analyzed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the MMSE. Psychiatric and behavioral disturbances were analyzed using the Neuropsychiatric Inventory (NPI) and the ADAS-Noncognitive subscale (ADAS-Noncog). The ability to perform instrumental and basic activities of daily living was evaluated using the Disability Assessment for Dementia (DAD) scale. Additionally, global state was assessed using the Clinician Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus) scale. RESULTS: After 26 weeks of metrifonate therapy, a statistically significant benefit of metrifonate was observed in the cognitive performance of Alzheimer's disease patients (ADAS-Cog, t = 2.55, df = 237, p = .012; MMSE, t = 4.60, df = 237, p = .0001). Metrifonate also significantly attenuated the deterioration in activities of daily living of the patients (DAD total score, t = -2.11, df = 233, p = .036) and relieved patients' psychiatric and behavioral disturbances (NPI total score, t = 2.51, df = 233, p = .013). In addition, metrifonate significantly improved the scores for the global state of the patients (CIBIC-Plus, t = 2.07, df = 232, p = .039). Metrifonate was well tolerated; adverse events were predominantly mild in intensity, and no hepatotoxicity was observed. CONCLUSION: In this study, metrifonate was safe and well tolerated. It benefited the cognitive decline, psychiatric and behavioral disturbances, impaired ability to perform instrumental and basic activities of daily living, and global state of patients diagnosed with mild-to-moderate Alzheimer's disease.     

卡巴拉汀治疗阿尔茨海默病患者的临床研究

目的：评价卡巴拉汀治疗中国轻中度阿尔茨海默病（AD）患者的有效性和安全性,方法：多中心、随机、开放、对照试验,共有124例50例以上轻中度AD患者,简易精神状态检查表（MMSE）得分在10－26分之间,并随机分为两组（卡巴拉汀组和多奈哌齐组各62例）。治疗时间16周。疗效评价使用MMSE量表、Blessed-Roth量表和总体衰退量表（GDS）在筛查和16周末进行。用Hachinski缺血积分量表鉴别AD和血管性痴呆（VD）,安全性检查包括生命体征,实验室及心电图检查,每4周1次。结果：两组的人口统计学有可比性（P＞0．05）。两组MMSE、GDS和Blessed-Roth评分均有显著改善（P＜0．01）。Blessed-Roth分值自身对比发现卡巴拉汀组显著改善日常生活能力（P＜0．01）;治疗前后的差值比较也发现卡巴拉汀组在社会活动能力方面稍优于多奈哌齐组（P＝0．0592）其他量表指标两组间差异无显著意义（P＜0．05）。总的不良反应率在12．9％－28．8％之间,两组间无显著差异,药物对病人生命体征及实验室指标无影响,结论：卡巴拉汀可显著改善AD患者的临床症状,且安全性和耐受性良好,是AD治疗的理想药物之一。     

首次确诊帕金森病患者情绪和认知功能障碍的关系

目的观察研究首次确诊帕金森痛患者情绪和认知功能障碍之间的关系。方法60例首次确诊帕金森病（PD）患者,采用简易智能状态检查量表（MMSE）和词ir-流畅性测验评定患者的认知功能;采用汉密尔顿抑郁量表（HAMD）和汉密尔顿焦虑量表（HAMA）评定患者的情绪障碍。采用统一帕金森病评分量表（UPDRS）和改良Hoehn—Yahr分级评定患者的帕金森病严重程度。结果（1）60例首次确诊PD患者改良H0ehn～Yahr分级显示：I级11例,Ⅱ级32例,Ⅲ级16例,Ⅳ级1例。其中具有抑郁障碍患者28例,占46．7％;具有焦虑障碍患者20例,占33．3％,20例焦虑障碍PD患者都具有抑郁障碍。（2）60例首次确诊PD患者中,具有认知功能障碍患者23例,占38．3％;MMSE评分和词汇流畅性测验评分均与病程呈负相关,差异具有统计学意义（r分别为-0．42,-0．46;P〈0．05）。（3）60例首次确诊PD患者HAMD评分和MMSE评分及词汇流畅性测验评分呈负相关,差异具有统计学意义（r分别为-0．69,-0．76;P〈0．01）。PD患者HAMA评分和MMSE评分及词汇流畅性测验评分亦呈负相关,差异具有统计学意义（r分别为～0．60,-0．68;P〈0．01）。结论首次确诊PD患者多为轻、中度患者,早期即表现情绪障碍和认知功能障碍,且两者具有高度相关性。