自然人群中老年人轻度认知障碍的随访研究

目的　研究自然人群中老年人轻度认知障碍 (MCI)向痴呆和阿尔茨海默病 (AD)的转化率。方法　以北京市 1997年痴呆患病率调查的样本人群为研究对象 ,对患病率调查时经简易智能状态检查法筛查、标准化神经心理测试和临床评估后诊断为MCI以及认知正常的受试者进行随访。比较MCI和认知正常受试者转化为痴呆和AD的转化率。结果　 12 1例MCI和 2 81名认知正常受试者平均随访大约 3年。MCI向痴呆和AD的平均年转化率分别为 14 1·10 0 -1·年-1和 8 0·10 0 -1·年 -1。认知正常受试者向痴呆和AD的平均年转化率分别为 1 6·10 0 -1·年 -1和 1 1·10 0 -1·年 -1。MCI转化为痴呆或AD的相对危险性分别为认知正常者的 9倍和 6倍。结论　MCI转化为痴呆的危险性远远大于认知正常的受试者。在未来开展痴呆人群综合防治的研究中 ,MCI是值得高度重视的人群。     

Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up

OBJECTIVE: This study evaluated the predictive utility of olfactory identification deficits in patients with mild cognitive impairment for follow-up diagnosis of probable Alzheimer's disease. METHOD: Ninety outpatients with mild cognitive impairment were examined at 6-month intervals. Matched healthy comparison subjects (N=45) were examined annually. The University of Pennsylvania Smell Identification Test was given at baseline. RESULTS: Olfaction scores were lower in patients with mild cognitive impairment than in healthy comparison subjects. Seventy-seven patients were followed up; 19 were diagnosed with Alzheimer's disease by 2 years. Patients with low olfaction scores (< or =34 of 40), and patients with low olfaction scores who reported no subjective problems smelling, were more likely to develop Alzheimer's disease than other patients. In a Cox proportional hazards model adjusted for age, sex, modified Mini-Mental State score, and education, low olfaction scores did not predict time until development of Alzheimer's disease, but low olfaction scores accompanied by lack of awareness of olfactory deficits predicted time to development of Alzheimer's disease. This effect remained when attention or memory measures replaced modified Mini-Mental State score in the model. In patients with high Mini-Mental State scores (> or =27 of 30), low olfaction with lack of awareness remained a significant predictor of Alzheimer's disease. Olfaction scores of 30-35 showed moderate to strong sensitivity and specificity for diagnosis of Alzheimer's disease at follow-up. CONCLUSIONS: In patients with mild cognitive impairment, olfactory identification deficits, particularly with lack of awareness of olfactory deficits, may have clinical utility as an early diagnostic marker for Alzheimer's disease.     

Platelet amyloid precursor protein abnormalities in mild cognitive impairment predict conversion to dementia of Alzheimer type: a 2-year follow-up study

BACKGROUND: Alteration of the amyloid precursor protein (APP) forms ratio has been described in the platelets of patients with dementia of Alzheimer type (DAT) and in a subset of subjects with mild cognitive impairment (MCI). OBJECTIVE: To evaluate the potential role of the platelet APP forms ratio in predicting progression from MCI to DAT. DESIGN: Thirty subjects with MCI underwent a clinical and neuropsychological examination and a determination of the platelet APP forms ratio. Subjects were followed up periodically for 2 years, and the progression to dementia was evaluated. SETTING: Community population-based sample of patients admitted for memory complaints. RESULTS: Patients who progressed to DAT at the 2-year follow-up (n = 12) showed a significant decrease of baseline platelet APP forms ratio values (mean +/- SD, 0.36 +/- 0.28) compared with stable MCI subjects (mean +/- SD, 0.73 +/- 0.32) (P<.01) and patients who developed other types of dementia (mean +/- SD, 0.83 +/- 0.27) (P =.03). By fixing a cutoff score of 0.6, 10 (83%) of the 12 DAT patients showed baseline values below the cutoff, whereas 10 (71%) of 14 subjects who either developed non-Alzheimer-type dementia or maintained cognitive functions had values in the normal range. CONCLUSION: Mild cognitive impairment is a major risk factor for DAT, and Alzheimer disease-related pathological changes can be identified in patients converting to DAT within a 2-year follow-up.     

Progression to dementia in a population with amnestic mild cognitive impairment: clinical variables associated with conversion

The aim of this study was to investigate clinical predictors of, and rates of conversion to, dementia syndrome in a case series of patients with amnestic mild cognitive impairment (aMCI). Two hundred and eight aMCI subjects were followed over a six-year period. A lower Mini Mental State Examination score was a significant predictor of dementia, and mild cognitive impairment patients with behavioral and psychiatric symptoms showed a faster conversion rate.     

Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer's disease: a one-year follow-up study

OBJECTIVE: To evaluate the relation between apathy and development of dementia in patients with amnestic mild cognitive impairment (MCI). METHODS: Two hundred and fifty-one French-speaking outpatients fulfilling the criteria of amnestic MCI were enrolled. Apathy was assessed with the Apathy Inventory (IA). Neuropsychiatric evaluation also included the Goldberg anxiety scale and the Montgomery and Asberg Depressive Rating Scale (MADRS). The main end point considered after a 1-year follow-up was the development of dementia of Alzheimer type (DAT). RESULTS: At baseline there were 86 (39.8%) subjects presenting at least one symptom of apathy among the 216 included in analysis. After a 1-year follow-up, 22 patients developed DAT. Of the patients with apathy at baseline 13 (15.1%) developed DAT in comparison with 9 (6.9%) of the non-apathetic patients. At the 1-year follow-up, patients developing DAT had a significantly higher frequency of apathetic symptoms (91.7%) than patients without DAT (26.9%). CONCLUSION: Taking into account that apathy is one of the most frequently observed neuropsychiatric symptoms in MCI and in DAT the present study suggests that patients with MCI and apathy should be more closely observed.     

轻度认知障碍与无痴呆型血管性认知障碍患者的神经心理学特征

阿尔茨海默病（AD）和血管性痴呆（vascular dementia，VD）是临床常见的老年期痴呆类型。虽然长期以来受到广泛关注．但对其治疗收效甚微．近年逐渐将研究重点转向对其早期阶段的干预治疗。在这一临床需要下，针对阿尔茨海默病和血管性痴呆分别提出了轻度认知障碍（mild cognitive impairment，MCI）和血管性认知障碍（vascular cognitive impairment，VCI）的概念，力求对患者进行早期识别和干预，以延缓甚至阻止痴呆的发生、发展。     

Impact of cognitive impairment on mild dementia patients and mild cognitive impairment patients and their informants

BACKGROUND: The aim of this study was to identify key aspects of the impact of cognitive impairment on patients with mild cognitive impairment (MCI) and mild probable Alzheimer disease (AD) and their informants, and identify overlap and differences between the groups. METHODS: Structured focus group discussions were conducted with MCI patients, AD patients, MCI informants, and AD informants. Participants were recruited from memory clinics in the U.K. and the U.S.A. A total of 20 AD and 20 MCI patients and 16 AD and 11 MCI informants participated. Sessions were content reviewed to identify key impacts of cognitive impairment; results were compared across diagnostic groups and for patients and informants. RESULTS: Seven key themes emerged: uncertainty of diagnosis, skill loss, change in social and family roles, embarrassment and shame, emotionality, insight, and burden. Patients were able to discuss the impact of cognitive impairment on their lives and reported frustration with recognized memory problems, diminished self-confidence, fear of embarrassment, concerns about changing family roles due to cognitive impairment, and anxiety. Informants reported more symptoms and more impairment than did patients and indicated increased dependence on others among patients. CONCLUSION: MCI and mild AD exert substantial burden on patients' lives and the lives of those close to them.     

遗忘型轻度认知功能障碍的执行功能损害

目的探讨遗忘型轻度认知功能障碍患者执行功能变化的特点。方法依据Miyake的执行功能三因素模型(工作记忆、任务转换、反应抑制),使用E-prime软件对这三种执行功能核心成分编写检测任务:利用2-back任务和Keep-track任务检测工作记忆,Stop-signal任务和Stroop任务检测反应抑制,More-odd shift-ing任务检测任务转换能力。在34例遗忘型轻度认知功能障碍(amnestic mild cognitive impairement,aMCI)患者和31例正常老年人中进行这些任务的检测,比较两组间执行功能差异的特点。结果 aMCI组的执行功能比对照组显著降低(Wilks′λ=0.567,P﹤0.01)。除Stroop任务的数据两组间没有明显差异之外,aMCI组的2-back任务、Keep-track任务、Stop-signal任务、More-odd shifting任务的成绩均显著低于对照组(P<0.05),但这4种任务成绩下降的程度彼此间没有显著差异。结论aMCI阶段已经出现了执行功能的全面损害,三种执行功能核心成分均有受损。     

Functional deficits in patients with mild cognitive impairment: prediction of AD

OBJECTIVE: To evaluate the predictive utility of self-reported and informant-reported functional deficits in patients with mild cognitive impairment (MCI) for the follow-up diagnosis of probable AD. METHODS: The Pfeffer Functional Activities Questionnaire (FAQ) and Lawton Instrumental Activities of Daily Living (IADL) Scale were administered at baseline. Patients were followed at 6-month intervals, and matched normal control subjects (NC) were followed annually. RESULTS: Self-reported deficits were higher for patients with MCI than for NC. At baseline, self- and informant-reported functional deficits were significantly greater for patients who converted to AD on follow-up evaluation than for patients who did not convert, even after controlling for age, education, and modified Mini-Mental State Examination scores. While converters showed significantly more informant- than self-reported deficits at baseline, nonconverters showed the reverse pattern. Survival analyses further revealed that informant-reported deficits (but not self-reported deficits) and a discrepancy score indicating greater informant- than self-reported functional deficits significantly predicted the development of AD. The discrepancy index showed high specificity and sensitivity for progression to AD within 2 years. CONCLUSIONS: These findings indicate that in patients with MCI, the patient's lack of awareness of functional deficits identified by informants strongly predicts a future diagnosis of AD. If replicated, these findings suggest that clinicians evaluating MCI patients should obtain both self-reports and informant reports of functional deficits to help in prediction of long-term outcome.     

轻度认知损害向老年性痴呆转化的临床研究

目的 研究轻度认知损害(mild cognitive impairment,MCI)向痴呆自然转化过程及多奈哌齐对转化的干预影响.方法 总结98例MCI患者情况,将服用多奈哌齐和未服用任何胆碱酯酶抑制剂的遗忘型MCI(aMCI)及非aMCI患者按年龄、性别、认知减退程度及ApoEε4携带情况分层配对研究,分析各组向痴呆转化率以及MMSE、阿尔茨海默病(AD)评定量表(ADAS-Cog)和aMCI组修订韦氏记忆量表(WMS-R)变化.结果 由aMCI向AD转化率,服用和未服用多奈哌齐组于1年时分别为15.1%和8.3%(P＜0.05),2年时分别为24.2%和12.5%(P＜0.01).由非aMCI向AD转化率,服用和未服用多奈哌齐组,于1年时分别为13.0%和5.5%(P＜0.05),2年时分别为21.7%和16.6%(P＜0.05).服用多奈哌齐6个月时,aMCI组MMSE提高(0.1±1.3)分,对照组下降(0.3±2.4)分;ADAS-Cog下降(1.4±4.7)分,对照组升高(0.03±4.55)分;WMS-R改善(4.8±4.1)分,对照组下降(3.7±5.2)分,治疗组与自然病程对照组比较差异有统计学意义(P＜0.01),并可维持1～2年.多奈哌齐还能延缓携带ApoEε4的MCI患者向AD转化,但与自然病程组比较无统计学意义(P＞0.05),尚有待扩大样本量继续研究观察.多奈哌齐对认知相关区脑萎缩有减缓趋势.结论 本组资料提示,多奈哌齐能推迟MCI向AD转化.     

A two-year follow-up of cognitive deficits and brain perfusion in mild cognitive impairment and mild Alzheimer's disease

The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimer's disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI.     

Amyloid deposition and CBF patterns predict conversion of mild cognitive impairment to dementia

Mild cognitive impairment (MCI) can include the transition from a normal state to dementia. To explore biomarkers for the development of dementia, we performed an 18-month follow-up study in 28 patients with amnestic MCI. Amyloid deposition was examined using PiB PET, and cerebral blood flow (CBF) was examined using SPECT. Cognitive function was periodically assessed. The rate of conversion to dementia was higher in the PiB-positive/equivocal group (74%) than in the PiB-negative group (33%) (p?=?0.041). Perfusion SPECT was performed in 16 patients. MCI patients with an AD-characteristic pattern of reduced CBF had a higher PiB-positive/equivocal rate (82%) than those with a non-AD pattern (20%) (p?=?0.018), and patients with an AD pattern had a higher conversion rate (82%) than those with a non-AD pattern (40%) (p?=?0.094). Clinically, all PiB-positive converters were diagnosed as having Alzheimer’s disease (AD), whereas PiB-negative converters were thought to have some form of dementia other than AD. Amyloid PET is useful for predicting conversion to AD in MCI patients. A pattern analysis of perfusion SPECT findings might also be helpful for predicting conversion to AD, but with a lower specificity.