Depressive symptoms in Alzheimer's disease: natural course and temporal relation to function and cognitive status

OBJECTIVES: To examine the natural course of depressive symptoms in patients with probable Alzheimer's disease (AD), specifically, the temporal relationship between depressive symptoms, function, and cognitive status. DESIGN: Multicenter cohort study with follow-up of up to 14 years. SETTING: Patients from the two Multicenter Study of Predictors of Disease Course in Alzheimer's Disease (Predictors Study) cohorts were recruited at five sites in the United States and Europe. PARTICIPANTS: Patients diagnosed with probable AD (n=536) enrolled in a longitudinal study (Predictors Study). MEASUREMENTS: Depressive symptoms were evaluated at 6-month intervals using the Columbia Scale for Psychopathology in Alzheimer's Disease. The Modified Mini-Mental State (3MS) and Blessed Dementia Rating Scale (BDRS) were used to assess cognitive status and functional activity, respectively. RESULTS: The prevalence of depressive symptoms was stable over the first 3 years of follow-up, at approximately 40%. There was a significant drop to 28% and 24% in the fourth and fifth years of follow-up, respectively. Time-dependent Cox analysis revealed that functional activity (BDRS) but not cognitive status (3MS) was a significant predictor of the first episode of depressive symptoms during follow-up. Generalized estimating equation analyses showed that AD duration and functional activity but not cognitive status were significantly related to depressive symptoms over the entire follow-up period. CONCLUSION: Depressive symptoms are common in AD, but their prevalence decreases over time. Examination of the temporal relationship between depressive symptoms and risk factors suggests that decline in function but not in cognition precedes the first episode of depressive symptoms in patients with probable AD.     

Does a depression intervention result in improved outcomes for patients presenting with physical symptoms?

OBJECTIVE: To investigate the effects of exclusively physical presentation of depression on 1). depression management and outcomes under usual care conditions, and 2). the impact of an intervention to improve management and outcomes. DESIGN AND SETTING: Secondary analysis of a depression intervention trial in 12 community-based primary care practices. PARTICIPANTS: Two hundred adults beginning a new treatment episode for depression. MEASUREMENTS: Presenting complaint and physician depression query at index visit; antidepressant use, completion of adequate antidepressant trial, change in depressive symptoms, and physical and emotional role functioning at 6 months. MAIN RESULTS: Sixty-six percent of depressed patients presented exclusively with physical symptoms. Under usual care conditions, psychological presenters were more likely than physical presenters to complete an adequate trial of antidepressant treatment but experienced equivalent improvements in depressive severity and role functioning. In patients presenting exclusively with physical symptoms, the intervention significantly improved physician query (40.8% vs 18.0%; P =.06), receipt of any antidepressant (63.0% vs 20.1%; P =.001), and an adequate antidepressant trial (34.9% vs 5.9%; P =.004), but did not significantly improve depression severity or role functioning. In patients presenting with psychological symptoms, the intervention significantly improved receipt of any antidepressant (79.9% vs 38.0%; P =.01) and an adequate antidepressant trial (46.0% vs 23.8%; P =.004), and also improved depression severity and physical and emotional role functioning. CONCLUSIONS: Our results suggest that there is a differential intervention effect by presentation style at the index visit. Thus, current interventions should be targeted at psychological presenters and new approaches should be developed for physical presenters.     

Depressive symptoms and level of physical activity in patients with Alzheimer's disease

Aim: The purpose of this study was to determine the presence of depressive symptoms in patients with Alzheimer's disease, to assess whether there was an association between physical activity level and depressive symptoms in this population, and to assess whether more active patients had lower rates of depressive symptoms when compared with less active patients. Methods: The study included 37 patients with Alzheimer's disease and used the following instruments: the Geriatric Depression Scale, the Cornell Scale for Depression in Dementia and the Baecke Questionnaire Modified for the Elderly. The Shapiro–Wilk test was used to determine whether the data were normally distributed. The Spearman correlation test and the Mann–Whitney U‐test was used. P‐values less than 5% were considered statistically significant. Results and discussion: The prevalence of depressive symptoms in the sample was 35.13%. The Spearman correlation test verified the relationship between level of physical activity and depressive symptoms (rho = ?0,4), and between the sports activities domain and depressive symptoms (rho = ?0,4). Patients who were more active had lower depressive symptoms. Conclusions: The prevalence of depressive symptoms in the sample was 35.13%. Patients who were more active had lower rates of depressive symptoms. Geriatr Gerontol Int 2012; ??: ??–??.     

Thiamine therapy in Alzheimer's disease

Fursultiamine (TTFD), a derivative of thiamine, at an oral dose of 100 mg/day had a mild beneficial effect in patients with Alzheimer's disease in a 12-week open trial. The improvement could be observed not only in their emotional or other mental symptoms but also in intellectual function. Only mildly impaired subjects showed cognitive improvement. Alzheimer patients' blood levels of thiamine before the trial were within the normal range. No adverse reactions were observed and all patients tolerated the trial well. TTFD could afford an alternate treatment to large doses of thiamine hydrochloride in Alzheimer patients. However, further investigations of the therapeutic implications of thiamine and its possible etiologic clues to Alzheimer's disease are necessary.     

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阿尔茨海默病是最常见的老年认知障碍,本文着重对阿尔茨海默病的治疗研究领域中的热点进行点评,包括Aβ聚集抑制剂、Aβ生成抑制剂、Aβ介导的神经递质抑制剂、Tau介导的神经毒性抑制剂等。对在困境中的AD治疗研究如何进一步深入,提出需要重新审视的问题。     

快速眼动期睡眠行为障碍与帕金森病的关联及其早期生物学标志物的研究

目的 探讨帕金森病（PD）潜在的早期生物学标志物在快速眼动期睡眠行为障碍（RBD）患者与PD患者之间的关联与差异.方法 采用统一帕金森病评定量表（UPDRS）、简易智能精神状态检查量表（MMSE）、汉密尔顿抑郁量表（HAMD-17）、帕金森病自主神经功能量表（SCOPA-AUT）、RBD筛查问卷（RBDSQ）对10例特发性RBD患者、15例PD伴RBD患者、15例PD不伴RBD患者和10例健康对照者进行运动症状及非运动症状的评定,并将上述指标在4组间进行组间比较及相关分析.结果 SCOPA-AUT评定结果显示,特发性RBD患者的非运动症状评分介于正常对照与PD患者之间（P＜0.05）,且所有被试者SCOPA-AUT评分与RBDSQ评分呈显著正相关（R=0.561,P＜0.05）.HAMD-17、MMSE评分在4组间比较差异无统计学意义（P＞0.05）,且与RBDSQ评分相关性无统计学意义（P＞0.05）.结论 RBD与PD密切相关,特发性RBD患者自主神经功能症状的严重程度介于正常对照与PD患者之间,提示自主神经功能症状有可能成为预测RBD患者发展成为PD风险的潜在生物学标记物.     

阿尔茨海默病患者精神行为异常与脑白质损害的相关性

目的 探讨阿尔茨海默病(Alzheimer's disease,AD)患者精神行为异常与脑白质损害的相关性.方法 纳入60例60岁以上的AD患者(AD组)和40例年龄、性别相匹配的认知功能正常的老年人(对照组),盲法分析其CT资料,双侧额区、顶枕区、颞区和幕下共8个区域白质损害的总和作为白质损害的总分,并检测CT显示的脑血管病变.AD组分别进行神经精神科问卷评分(Neuropsychiatric Inventory,NPI).结果 AD组脑白质损害总分、左额区、右额区、左顶枕区、右顶枕区白质损害和脑血管病变分别为1.450±2.310、0.340±0.340、0.310±0.560、0.240±0.360、0.140±0.230和0.120±0.330,而对照组分别为9.640±1.566、1.720±0.248、1.680±0.312、1.550±0.244、0.140±0.230和2.230±0.378,两组有显著差异(P分别为0.000、0.001、0.001、0.012、0.006和0.002).Spearman相关分析表明,NPI与白质损害总评分、左额区、右额区、左顶枕区和右顶枕区白质损害评分相关,rs(P)分别为0.487(0.016)、0.490(0.014)、0.502(0.014)、0.507(0.012)和0.521(0.014),而与脑血管病变无关(rs=0.132,P=0.590).结论 脑白质损害和脑血管病变对AD的发病及病情发展至关莺要,脑白质损害与AD患者的精神行为异常密切相关.     

Impediments to timely diagnosis of Alzheimer's disease in African Americans

The purpose of this study was to identify early patterns of care for Alzheimer's disease (AD) in a cohort of African-American patients and their caregivers presenting at an inner city clinic and a suburban memory assessment clinic. Caregivers (N=79) of patients diagnosed with probable AD were interviewed. Data were collected about the delay from noticing first AD signs until recognition that a problem existed and delay from problem recognition until first physician consultation. Patients and caregivers had lower educational status, and patients had been diagnosed more recently at the inner city clinic than at the suburban clinic, although MMSE scores of patients at the two clinics did not differ; median delays in caregivers' recognizing a problem and in consulting a physician were also similar across clinics. Delay was as long as 7 years between noticing symptoms and problem recognition and between problem recognition and physician consultation. Although patients attending the suburban clinic were more likely to have previously seen a physician than those attending the inner city clinic, they were no more likely to have received a prior diagnosis of AD. Lack of physician contact is likely to be widespread in families caring for African Americans with AD. Physician consultation is more characteristic of more highly educated families but may not yield a correct diagnosis for the patient. Intensive efforts are needed to connect African-American families with physicians and to achieve more timely diagnosis of AD to enable families to understand the illness, plan for patient safety, and make long-term plans.     

维生素E对Alzheimer病模型大鼠的影响

采用ＡｌＣｌ３诱导，建立Ａｌｚｈｅｉｍｅｒ病（ＡＤ）模型大鼠。用维生素Ｅ（ＶＥ）（５ｍｇ／１００ｇ体重·ｄ－１）对ＡＤ模型大鼠进行灌胃治疗。通过行为测试，光镜形态学观察，用免疫细胞化学ＡＢＣ结合图像定量分析的方法，对ＡＤ大鼠行为改变，海马结构ＣＡ１区淀粉样蛋白免疫反应阳性神经元的形态和数目、胞体平均截面积和光密度以及β淀粉样蛋白的沉积变化进行观察。结果显示ＶＥ组大鼠治疗３个月和５个月后，受电击次数和潜伏期较对照组明显减少和延长（Ｐ＜００１），３个月与５个月之间有显著性差异（Ｐ＜００１）；ＶＥ组大鼠海马结构ＣＡ１区淀粉样蛋白免疫反应阳性神经元的形态和数目、胞体平均截面积和光密度值，３个月和５个月较对照组均有明显减少和降低（Ｐ＜００１），３个月和５个月之间也有显著性差异（Ｐ＜００１），β淀粉样蛋白样反应染色减少或消失。说明ＶＥ可以改善ＡＤ模型大鼠的学习记忆，其作用机制是通过抑制和清除海马结构ＣＡ１区β淀粉样蛋白的沉积来实现的，作用效果随治疗时间的延长而更加明显。本实验研究结果为临床应用ＶＥ治疗老年性痴呆提供了形态学依据。     

阿尔茨海默病与血管性痴呆的非认知功能损害

目的　观察阿尔茨海默病与血管性痴呆的患者除认知功能异常外 ,是否存在非认知功能的异常。方法　根据DSM -Ⅳ阿尔茨海默病及血管性痴呆的诊断标准以及CDR的临床痴呆分级标准 ,对神经内科老年记忆障碍专科病房的 2 1例轻中度阿尔茨海默病及 2 5例血管性痴呆患者的非认知功能损害的临床表现进行了观察 ,包括情感反应、行为异常、人格变化及知觉异常。结果　阿尔茨海默病患者的非认知功能损害在情感障碍 (16例 ,76 % )、人格异常 (10例 ,48% )及知觉异常 (6例 ,2 9% )方面 ,明显多于血管性痴呆组 (分别为 10例 ,40 % ;1例 ,4% ;1例 ,4% )。结论　痴呆患者不仅有认知功能的损害 ,还有非认知功能的损害。阿尔茨海默病的非认知功能损害重于血管性痴呆 ,可能与两种痴呆的发病机制不同有关。     

Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort

OBJECTIVES: To determine whether coronary artery disease, peripheral arterial disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the onset of dementia and Alzheimer's disease (AD). DESIGN: Longitudinal cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Men and women (N=3,602) with a brain magnetic resonance imaging (MRI) scan but no dementia were followed for 5.4 years. Participants with stroke were excluded. MEASUREMENTS: Neurologists and psychiatrists classified incident cases of dementia and subtype using neuropsychological tests, examination, medical records and informant interviews. CVD was defined at the time of the MRI scan. Noninvasive tests of CVD were assessed within 1 year of the MRI. Apolipoprotein E allele status, age, race, sex, education, Mini-Mental State Examination score, and income were assessed as potential confounders. RESULTS: The incidence of dementia was higher in those with prevalent CVD, particularly in the subgroup with PAD. The rate of AD was 34.4 per 1,000 person-years for those with a history of CVD, versus 22.2 per 1,000 person-years without a history of CVD (adjusted hazard ratio (HR)=1.3, 95% confidence interval (CI)=1.0-1.7). Rates of AD were highest in those with PAD (57.4 vs 23.7 per 100 person-years, adjusted HR=2.4, 95% CI=1.4-4.2). Results were similar with further exclusion of those with vascular dementia from the AD group. A gradient of increasing risk was noted with the extent of vascular disease. CONCLUSION: Older adults with CVD other than stroke had a higher risk of dementia and AD than did those without CVD. The risk was highest in people with PAD, suggesting that extensive peripheral atherosclerosis is a risk factor for AD.     

扩瞳试验在Alzheimer病诊断中的意义

目的　探讨扩瞳试验在Alzheimer病 (AD)诊断中的意义。　方法　在滴入 0 0 1%托吡卡胺 7～ 10min后 ,用双侧瞳孔红外线同步记录分析仪自动记录并分析滴药眼的瞳孔直径扩大程度(按对照侧校正 )。共测定AD 5 2例 ,血管性痴呆 (VD) 33例和健康对照 (HC) 5 8例。利用受试者工作特性曲线 (ROC)确定最能明显区别AD与HC的分界线 ,计算敏感度、特异度和Kappa值 ,评估扩瞳试验的诊断价值。　结果　 ,AD患者滴药眼的瞳孔明显扩大 ,与VD或HC差异有极显著性 (P <0 0 1) ,其中以第 18min时的差别最为显著。如以瞳孔扩大 15 %作为分界线 ,敏感度均为 0 81,特异度分别为 0 82和 0 79,Kappa值分别为 0 6 7和 0 6 0。　结论　扩瞳试验可以作为筛选早期AD的一个手段 ,也可在鉴别AD与VD时作参考。     

Apolipoprotein E genotyping in Alzheimer's disease in an Australian sample

Background: Several previous studies have reported an increased frequency of the E4 allele of the gene for Apolipoprotein (APOE4) in both familial and sporadic Alzheimer's disease (AD). We report the results of a study of this association in an Australian clinic-based sample. Aim: To investigate the relationship between APOE4 frequency and AD in an Australian clinic-based sample and compare the results with previous studies. Methods: Subject DNA was PCR amplified, enzymatically digested with Hhal and the resulting fragments electrophoretically separated. The genotypes were ascertained according to the resulting fragment sizes and the resulting allele frequencies analysed by calculating a z-statistic for comparison of two proportions. Results: The frequency of the APOE4 allele was 53% in the AD group and 11% in the control group. This difference is statistically significant. There was no significant difference in E4 allele frequencies between AD subjects with a family history and those without. At least one E4 allele was found in 26/30 (87%) of AD patients and 10/50 (20%) of controls. The allele frequencies of the control subjects used in this study were found to be consistent with those of several previous studies. Conclusion: The frequency of the APOE4 allele was significantly higher in AD subjects than in unaffected controls. This provides further evidence of an association between APOE4 and both familial and sporadic AD.     

Development of a scale to predict decline in patients with mild Alzheimer's disease

OBJECTIVES: To develop a scale that can assist in predicting likelihood of decline from mild dementia over 1 year in patients with Alzheimer's disease (AD). DESIGN: Retrospective cohort study. SETTING: University Memory and Aging Center. PARTICIPANTS: Patients with probable or possible AD and Clinical Dementia Rating (CDR) of 1 at baseline, divided into development and validation cohorts (n = 118 each). MEASUREMENTS: The CDR and neurological and neuropsychological assessments were given at baseline and 1 year later. RESULTS: In the development cohort, high education, low Mini-Mental State Examination score, poor insight, psychotic symptoms, and greater activity of daily living impairment predicted decline in CDR from 1 to 2 or 3. Receiver operating characteristics (ROC) curve analysis identified cutoff scores that maximized sensitivity and specificity for each significant predictor of decline. Based on the cutoff, raw scores were recoded to reflect risk for decline, weighted, and summed to create a final scale score. ROC curve analysis established a cutoff to indicate risk for decline on the final scale score. Sensitivity, specificity, and area under the ROC were 0.76, 0.74, and 0.83 in the development cohort and 0.77, 0.69, and 0.80 in the validation cohort, respectively. Positive and negative predictive values were 0.71 and 0.78 in the development cohort and 0.68 and 0.78 in the validation cohort, respectively. CONCLUSIONS: Decline from mild to moderate or severe impairment represents significant clinical change, with implications for patient and caregiver quality of life and treatment options. The clinical scale developed uses data to enhance prediction about change from mild to moderate or severe stages of AD.     

Prediction of on-road driving performance in patients with early Alzheimer's disease

OBJECTIVES: Physicians and family members frequently are asked to provide information about driving ability in patients with Alzheimer's disease (AD), yet there has been little research on the validity of their assessments of driving performance. DESIGN: Cross-sectional. SETTING: Participants were recruited from the neurology department of a community hospital affiliated with Brown Medical School. PARTICIPANTS: Participants included 75 older adults (17 with mild AD, 33 with very mild AD, and 25 elderly controls). MEASUREMENTS: The participant him/herself, an informant, and an experienced neurologist rated each participant's driving ability on a 3-point rating scale (safe, marginal, unsafe). A professional driving instructor also completed a standardized 108-point on-road driving assessment of each participant and then rated driving ability on the 3-point scale. Ratings were compared with the on-road driving score and with each other. RESULTS: Only the neurologist's rating of the participants' driving abilities was significantly related to on-road driving score. When related to the instructor's safety rating, the neurologist's ratings were the most sensitive and specific. Mini-Mental State Examination score was a borderline covariate for the neurologist's rating. Overall, the instructor was the most stringent rater of participant driving ability, followed by the neurologist, the informant, and the participant. CONCLUSION: An experienced neurologist's assessment of driving competence may be a valid predictor of driving performance of patients with early AD.     

Longitudinal patterns of unawareness of memory deficits in mild Alzheimer's disease

Aim:   Patients with Alzheimer's disease (AD) frequently demonstrate impaired awareness of their cognitive difficulties. However, less is known about the longitudinal progression of this phenomenon. We examined the longitudinal evolution of unawareness in patients with mild AD to determine whether impaired awareness progresses with cognitive decline.
Methods:   Based on Mini-Mental State Examination (MMSE) score changes after a 1-year follow up, 39 patients were regarded as the stabilized group and 19 patients were regarded as the non-stabilized group. The unawareness of memory impairment was evaluated with a standardized questionnaire system based on the Everyday Memory Checklist (EMC). The EMC scores for the patient's own rating, the caregivers' rating and the unawareness score, defined as the difference between these (caregiver rating – patient rating), were analyzed.
Results:   Although unawareness scores were similar in the two groups at the initial examination, they were significantly higher in the non-stabilized group than in the stabilized group at the follow up examination. There was a significant and negative correlation between change in unawareness score and change in MMSE score over time ( r  = −0.56, P  < 0.0001).
Conclusion:   Our results indicated that impaired awareness progressed with cognitive decline. The EMC may be a simple and useful tool for the monitoring of progression in patients with AD.     

多奈哌齐治疗阿尔茨海默病的远期疗效观察

目的 观察多奈哌齐治疗阿尔茨海默病(AD)的远期疗效和安全性. 方法 86例AD患者随机分为对照组43例和治疗组43例.对照组运用茴拉西坦、尼莫地平、银杏叶片进行常规治疗,治疗组在常规治疗的基础上每日加服多奈哌齐l0 mg.以简易智能状态检查量表(MMSE)、AD评估量表认知分量表(ADAS-cog)、日常生活能力量表(ADL)、总体衰退量表(GDS)等评分作为主要评价指标,比较两组患者在治疗前与治疗3、6、12、18、24、30、36、42、48、54、60、66和72个月后的认知能力、精神状况、日常生活能力的情况. 结果 与对照组比较,治疗组患者MMSE、ADAS-cog、GDS评分在3个月以后、ADL评分在6个月以后优于对照组,差异有统计学意义(t=2.361,-2.198,-1.790和-2.420;P＜0.05或P＜0.01);12个月时与对照组相比最显著(均P＜0.01),36个月以后各项指标继续减退,到72个月时,治疗组与对照组相比,MMSE高出7.5分,ADAS-cog优于20.3分,ADL优于19.5分,GDS优于1.4分(均P＜0.01).与治疗前比较,治疗组患者MMSE、ADAS cog、GDS评分在治疗3、6、12、18和24个月时差异有统计学意义(P＜0.05或P＜0.01);ADL评分在6、12、18、24和30个月时差异有统计学意义(P＜0.05或P＜0.01);ADAS-cog和GDS评分在24个月以后、MMSE和ADL在30个月以后差异无统计学意义(P＞0.05). 结论 多奈哌齐治疗AD的远期疗效满意,安全可靠,可有效减缓AD患者认知功能和总体功能衰退进程.     

Phosphofructokinase activity in fibroblasts from patients with Alzheimer's disease and age- and sex-matched controls

The activity of the enzyme phosphofructokinase (PFK) was comparable in cultured skin fibroblasts from eight patients with Alzheimer's disease and eight age- and sex-matched controls. Mean activities were similar in the two groups whether measured under nonallosteric conditions at pH 8.0 or under allosteric conditions at pH 7.0, in the presence of 0.1 or 1 mM ATP. Activities of PFK in Alzheimer's disease and control cells also showed a similar temperature dependence and similar isozyme patterns on column chromatography. These results argue against the existence of significant structural variations of PFK in Alzheimer's disease.     

轻度阿尔茨海默病持续性注意功能的相关性研究

目的 了解轻度阿尔茨海默病(AD)患者注意功能损害情况及其相关因素. 方法 对68例轻度AD病患者在入组时、入组治疗8周后和100例健康老年人进行了连续操作试验(CPT)测试,以简易精神状态量表(mini-mental state examination,MMSE)和AD病理行为评分表(BEHAVE-AD)评定病情,并对测试结果、病程、病情严重度、年龄等进行回归分析. 结果 AD患者的所有CPT指标视觉单目标持续性注意测验(VOT)、视觉连续目标持续性注意测验(VST)、听觉持续性注意测验(ET)的漏答率、误答率、反应时间和变异系数均高于健康对照组,人组治疗8周后略有好转,但仍比健康人高,人组时CPT结果与病程、病情严重程度有关. 结论 AD患者注意损害广泛而严重,注意损害与病程、精神行为症状有关.