轻度认知功能障碍与阿尔茨海默病患者血管危险因素的研究

目的 探讨血管危险因素与轻度认知功能障碍（Mild cognitive impairment,MCI）及阿尔茨海默病（Alzheimer＇sdisease,AD）的关系,并进一步分析各因素与认知功能下降程度的相关性.方法 选择2012年6月至2014年6月于门诊及住院部诊断为MCI及AD的患者各35例,同期体检的性别、年龄、文化程度相匹配的健康老人35例为对照.所有研究对象均进行MMSE、ADAS-Cog量表评定,采集晨空腹血进行血脂、血糖检测,并分别记录性别、年龄、身高、体重、吸烟、饮酒等情况.采用最小显著性差异法（LSD）比较各组间血管危险因素的差异、Pearson＇s相关分析各因素与认知功能评分的相关性.结果 与对照组相比,MCI组、AD组体重指数、血胆固醇水平呈进行性下降,但仅AD组与对照组相比差异有统计学意义.收缩压水平MCI组、AD组与对照组相比均明显升高,MCI组与AD组比较差异亦有统计学意义.Pearson＇s分析可见各因素与认知功能下降程度之间呈线性相关.糖尿病、饮酒比率AD组与对照组相比亦明显升高.结论 血管危险因素在老年人认知功能下降过程中有重要的作用,并有可能指导AD早期诊断及治疗.     

18F-FDG和11C-PIB PET联合脑显像对阿尔茨海默病及 额颞痴呆的鉴别诊断价值初探

目的 初步探讨11C-PIB和18F-FDG联合脑显像在阿尔茨海默病（AD）及额颞痴呆（FTD）鉴别诊断中的 应用价值。方法 10例难以鉴别为AD或FTD的患者,行11C-PIB及18F-FDG PET联合脑显像。18例年龄匹配的健康 老年人为对照组,行18F-FDG PET脑显像。18F-FDG结果应用统计参数图（SPM）进行基于体素水平分析,行2个样本t 检验,P < 0.001认为有统计学意义。选取11C-PIB廓清及滞留情况对比明显的55~60 min图像进行视觉分析,PIB阳性 定义为双侧额叶、顶叶、枕叶、颞叶及皮质下结构PIB放射性滞留较白质为著,小脑PIB廓清。PIB阴性定义为大脑皮 层及皮质下结构、小脑无明显PIB滞留,仅在脑白质走行区少量放射性滞留。结果 18F-FDG与11C-PIB PET脑显像 示典型AD图像5例,双侧颞-顶联合皮质区、楔前叶及后扣带回大脑葡萄糖代谢减低,PIB阳性。典型FTD图像2例, 双侧额叶、前扣带回及双侧皮质下结构大脑葡萄糖代谢减低,PIB阴性。3例患者经18F-FDG脑显像仍难以鉴别,但 11C-PIB脑显像提示AD 2例,FTD 1例,并且经5~6个月随访证实。结论18F-FDG和11C-PIB联合脑显像能为AD及FTD 鉴别诊断提供双重的影像学依据,尤其是在大脑葡萄糖代谢减低脑区相互重叠时,11C-PIB显像有助于进一步鉴别。     

The status of ongoing trials for mild cognitive impairment

Mild cognitive impairment (MCI) is a term used to describe memory decline or other specific cognitive impairment in individuals who do not have dementia or significant impairment of other cognitive functions beyond that expected for their age or education. It has been suggested that as much as 38% of the elderly population would meet criteria for MCI and although the associated memory deficits are mild, the fact that up to 15% of MCI patients, particularly those with a particular type of memory impairment, convert to Alzheimer’s disease (AD) annually has prompted serious attention. Despite the high conversion rate, MCI cannot be used synonymously with early or mild AD, as patients with AD are impaired not only in memory performance but in other cognitive domains as well; they meet diagnostic criteria for dementia. However, since there is a high conversion rate from MCI to AD, it is likely many with MCI have the underlying neuropathology of AD, though they do not yet meet clinical diagnostic criteria. Therefore, treatment strategies developed for AD, specifically acetylcholinesterase inhibitors and Cox-2 inhibitors, have been among the first employed to treat MCI. It is hoped that by impeding the progression of MCI in this manner, fewer patients will convert to AD. This article will give a brief overview of the condition of mild cognitive impairment and an account of trial methodology and current treatment strategies being employed for MCI.     

The status of ongoing trials for mild cognitive impairment

Mild cognitive impairment (MCI) is a term used to describe memory decline or other specific cognitive impairment in individuals who do not have dementia or significant impairment of other cognitive functions beyond that expected for their age or education. It has been suggested that as much as 38% of the elderly population would meet criteria for MCI and although the associated memory deficits are mild, the fact that up to 15% of MCI patients, particularly those with a particular type of memory impairment, convert to Alzheimer's disease (AD) annually has prompted serious attention. Despite the high conversion rate, MCI cannot be used synonymously with early or mild AD, as patients with AD are impaired not only in memory performance but in other cognitive domains as well; they meet diagnostic criteria for dementia. However, since there is a high conversion rate from MCI to AD, it is likely many with MCI have the underlying neuropathology of AD, though they do not yet meet clinical diagnostic criteria. Therefore, treatment strategies developed for AD, specifically acetylcholinesterase inhibitors and Cox-2 inhibitors, have been among the first employed to treat MCI. It is hoped that by impeding the progression of MCI in this manner, fewer patients will convert to AD. This article will give a brief overview of the condition of mild cognitive impairment and an account of trial methodology and current treatment strategies being employed for MCI.     

Regional grey matter loss and brain disconnection across Alzheimer disease evolution

It is becoming increasingly clearer that the clinical manifestations of Alzheimer's disease (AD) are not only associated with regional grey matter (GM) damage, but also with abnormal integration between cortical brain regions by disconnection mechanism. This concept comes from the evidence that white matter (WM) damage (as assessed by diffusion MR imaging) can be observed in patients with AD since the early clinical stages, and it correlates with clinical measures of cognitive disability. In this perspective, several functional imaging studies, based on PET and resting state fMRI, have provided evidence that brain hypometabolism/disconnection may precede the occurrence of GM atrophy in certain regions of AD brains, such as the cingulate cortex. The cingulum represents the most prominent WM tract of the limbic system, being directly connected to the medial temporal lobe structures. Therefore, this structure likely contributes to changes in functional connectivity observed within the so called default-mode network of AD patients, and its damage is likely to play a remarkable role in the conversion from mild cognitive impairment (MCI) to dementia. Nowadays, the combination of several neuroimaging techniques that provide both, measures of regional GM loss and measures of functional and structural connectivity offer the opportunity to investigate in vivo the pathophysiological changes of brain tissue modifications across the clinical evolution of AD. This paper reviews the main MR based methods of investigation of brain tissue involvement in patients with AD and MCI, and the role they have played in clarifying the differential contribution of GM damage and brain disconnection to AD pathophysiology. This subject seems to be relevant for both, speculative aspects of neurology and application to clinical trials.     

轻度认知功能障碍患者后扣带回的磁共振扩散张量成像研究

目的 应用磁共振DTI分析轻度认知功能障碍（MCI）患者后扣带回脑白质各向异性分数（FA）值的变化,探讨DTI对轻度认知障碍的诊断价值.方法 选择观察组MCI患者与对照组健康志愿者各18例,应用GE Signa Excite 1.5 T 核磁共振系统进行头颅DTI检查,分别测量2组后扣带回、海马旁回及内囊后肢脑白质的FA值,比较2组测量结果.结果 观察组双侧后扣带回脑白质FA值显著低于对照组,差异有统计学意义（P〈0.05）;2组海马旁回、内囊后肢及胼胝体膝部FA值比较差异无统计学意义（P〉0.05）.结论 DTI作为早期诊断MCI的无创性检查手段,对早期干预及提高患者生存质量具有重要意义.     

Abnormal APP processing in platelets of patients with Alzheimer’s disease: correlations with membrane fluidity and cognitive decline

Rationale Previous studies have implicated platelet amyloid precursor protein (APP) as a candidate biomarker for Alzheimer’s disease (AD). Platelets contain more than 95% of the circulating APP and enclose the enzymatic machinery for the APP metabolism yielding both soluble APP and amyloid-β peptides. Objectives The objective of this study is to compare the ratio of 130- to 110-kDa fragments of APP in platelets from patients with AD, mild cognitive impairment (MCI), and elderly controls. Materials and methods After subjects were grouped according to diagnosis, APP ratio in platelets was evaluated by means of Western blot analysis. Results The APP ratio was significantly lower in AD patients (1.01 ± 0.21) as compared to controls (1.24 ± 0.21, p = 0.001) and MCI patients (1.18 ± 0.21, p = 0.027), but no significant differences were found between MCI and controls (p = 0.904). In addition, we found positive correlations between the APP ratio and 1,6-diphenyl-1,3,5-hexatriene anisotropy (r = 0.3, p = 0.01), as well as with certain parameters of cognitive decline, namely, the mini-mental state examination score (r = 0.33, p = 0.003), the total Cambridge cognitive test (CAMCOG) score (r = 0.37, p = 0.001), and the score on the memory subscale of the CAMCOG (r = 0.38, p = 0.001). Conclusions The pattern of platelet APP fragments was altered in patients with AD but not in patients with MCI. The alteration of APP fragments was correlated with membrane fluidity and the cognitive decline.     

老年阿尔茨海默病患者脑白质结构的扩散加权成像研究

目的:探讨磁共振扩散加权成像(DWI)评价阿尔茨海默病(AD)患者脑白质微结构改变的应用价值及该结构改变与患者认知功能损害的关系.方法:老年AD患者(AD组)及同期接受MRI检查无神经系统疾病或健康体检者(对照组)各30例,所有受检者均进行神经科查体和简易智能精神状态量表(MMSE)测试,对常规脑部MRI脑白质表现正常的部位行DWI检查,测量额叶白质、颞叶白质、顶叶白质、枕叶白质、胼胝体膝部和胼胝体压部6个兴趣区的平均弥散系数(ADC),并分析各部位ADC值与MMSE评分的关系.结果:AD组额叶自质、胼胝体压部、颞叶、顶叶的ADC值高于对照组(t分别为3.087、2.931、2.441和3.909,P＜0.05或P＜0.01),胼胝体膝部和枕叶ADC值与对照组比较差别无统计学意义(t分别为1.025和1.260,P＞0.05).AD组MMSE评分为(24.1±0.8)分,AD组顶叶白质、胼胝体压部、额叶白质的ADC值与MMSE评分呈负相关(r分别为-0.867、-0.670和-0.472,t分别为9.207,4.776,2.833,P＜0.05或P＜0.01),胼胝体膝部、颞叶白质、枕叶白质的ADC值与MMSE评分无直线相关性(r分别为-0.301、-0.308和-0.297,t分别为1.670,1.713,1.646,均P＞0.05).结论:对AD患者行定量DWI分析有助于评价AD常规MRI检查正常区域的微结构改变.老年痴呆患者认知功能的衰退与白质微结构密切相关,顶叶脑白质ADC值异常在认知功能损害早期更明显.     

Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease

OBJECTIVE: To evaluate the synergistic effects of the apolipoprotein E (APOE) epsilon4 and butyrylcholinesterase K-variant (BCHE-K) alleles on progression to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI). METHODS: This was a post-hoc exploratory analysis from a 3-4-year, randomized, placebo-controlled study of rivastigmine in participants with MCI (InDDEx study). Participants who consented to genetic testing were included in the current analyses. The incidence of progression to AD, cognitive decline and changes in MRI brain volumes were investigated in participants from the placebo arm of the InDDEx study. RESULTS: Of the 1018 participants in the overall study, 464 were successfully genotyped for both APOE and butyrylcholinesterase. Of these, 68 (14.7%) carried > or =1 APOE epsilon4 and > or =1 BCHE-K allele. The presence of APOE epsilon4 was associated with a significantly higher incidence of progression to AD whereas the presence of BCHE-K had no independent effect on progression. A synergistic effect of the combined presence of APOE epsilon4 and BCHE-K on the time to clinical diagnosis of AD and on MRI brain volumes was seen. Progression to AD and hippocampal volumetric loss was greatest in participants who carried both APOE epsilon4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE epsilon4 allele. CONCLUSION: In MCI, the risk of cognitive decline, hippocampal volumetric loss and progression to AD seems to be the greatest in individuals who carry at least one copy of both the BCHE-K and APOE epsilon4 alleles.     

Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline,Mild Cognitive Impairment,and Alzheimer’s Disease

BackgroundOdor identification (OI) dysfunction is an early marker of Alzheimer’s disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia.MethodsTwo hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls.ResultsFrom the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants.ConclusionStructural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.     

Blood D-Amino Acid Oxidase Levels Increased With Cognitive Decline Among People With Mild Cognitive Impairment: A Two-Year Prospective Study

BackgroundDysregulation of N-methyl-D-aspartate receptor (NMDAR) neurotransmission has been reported to be implicated in the pathogenesis of Alzheimer’s disease (AD). D-amino acid oxidase (DAO), responsible for degradation of NMDAR-related D-amino acids such as D-serine, regulates NMDAR function. A cross-section study found that serum DAO levels were positively related with the severity of cognitive aging among elderly individuals. This 2-year prospective study aimed to explore the role of DAO levels in predicting the outcome of patients with very early-phase AD, such as mild cognitive impairment (MCI).MethodsFifty-one patients with MCI and 21 healthy individuals were recruited. Serum DAO levels and cognitive function, measured by the AD assessment scale-cognitive subscale and the Mini-Mental Status Examination, were monitored every 6 months. We employed multiple regressions to examine the role of DAO concentration in cognitive decline in the 2-year period.ResultsFrom baseline to endpoint (24 months), serum DAO levels increased significantly, and cognitive ability declined according to both cognitive tests in the MCI patients. Among the healthy individuals, DAO concentrations also increased and Mini-Mental Status Examination scores declined; however, AD assessment scale-cognitive subscale scores did not significantly change. Further, DAO levels at both months 12 and 18 were predictive of cognitive impairment at month 24 among the MCI patients.ConclusionsTo our knowledge, this is the first study to demonstrate that blood DAO levels increased with cognitive deterioration among the MCI patients in a prospective manner. If replicated by future studies, blood DAO concentration may be regarded as a biomarker for monitoring cognitive change in the patients with MCI.     

阿尔茨海默病和轻度认知障碍常用实验动物模型的初步评价

阿尔茨海默病(AD)是一种典型的以进行性认知障碍和行为损害为特征的中枢神经退行性疾病,病理表现主要有细胞外淀粉样蛋白沉积、细胞内神经纤维缠结以及神经元丢失等。轻度认知障碍(MCI)是介于正常认知和AD之间的一种认知缺损状态,MCI具有转化为AD的高度危险性。以往大多通过建立具有临床AD特征的动物模型进行机制研究、药物筛选以及新药研发等,近年来,有研究者尝试建立具有临床MCI特征的动物模型,试图从MCI阶段进行早期干预,从而有效预防AD的发生。AD实验动物模型有多种类型,MCI研究模型应区别于AD模型。该文在对AD和MCI的特点进行较系统介绍的基础上,从模型建立的角度对常用AD和MCI实验动物模型进行了总结和初步评价,尝试为开展AD和MCI的研究提供建议。     

A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment.

Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and might be mediated via the COX-2 enzyme. Previous studies with the selective COX-2 inhibitors, rofecoxib and celecoxib, have shown that they do not alter the progression of AD. We conducted a double-blind study to investigate whether rofecoxib could delay a diagnosis of AD in patients with mild cognitive impairment (MCI), a group with an expected annual AD diagnosis rate of 10-15%. MCI patients > or =65 years were randomized to rofecoxib 25 mg (N=725) or placebo (N=732) daily for up to 4 years. The primary end point was the percentage of patients with a clinical diagnosis of AD. The estimated annual AD diagnosis rate was lower than the anticipated 10-15%: 6.4% in the rofecoxib group vs 4.5% in the placebo group (rofecoxib : placebo hazard ratio=1.46 (95% CI: 1.09, 1.94), p=0.011). Analyses of secondary end points, including measures of cognition (eg the cognitive subscale of the AD Assessment Scale (ADAS-Cog)) and global function (eg the Clinical Dementia Rating (CDR)), did not demonstrate differences between treatment groups. There was also no consistent evidence that rofecoxib differed from placebo in post hoc analyses comparing ADAS-Cog and CDR-sum of boxes scores in overlapping subgroups of patients who had Mini Mental State Exam scores of 24-26 in the present MCI study and in a previous AD treatment study with a similar design. The results from this MCI study did not support the hypothesis that rofecoxib would delay a diagnosis of AD. In conjunction with the lack of effects observed in previous AD studies, the findings suggest that inhibition of COX-2 is not a useful therapeutic approach in AD.     

Effects of lithium on brain glucose metabolism in healthy men

Lithium is clinically available for the treatment of mood disorders. However, it has remained unclear how lithium acts on the brain to produce its effects. The aim of this study was to evaluate the effects of chronic lithium on human brain activity using positron emission tomography and clarify the correlation between brain activity changes and cognitive functional changes as induced by chronic lithium administration. A total of 20 healthy male subjects (mean age, 32 +/- 6 years) underwent positron emission tomographic scans with F-fluorodeoxyglucose and a battery of neuropsychological tests at baseline condition and after 4 weeks of lithium administration. Brain metabolic data were analyzed using statistical parametric mapping. Lithium increased relative regional cerebral glucose metabolism (rCMRglc) in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased rCMRglc in the right cerebellum and left lingual gyrus/cuneus. There was no difference in any of the variables of cognitive functions between the baseline condition and after chronic lithium administration. There was no correlation between rCMRglc changes in any of the brain regions and individual variable changes in any of the neuropsychological tests. The results suggest that the effects of chronic lithium are associated with increased activity in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased activity in the right cerebellum and left lingual gyrus/cuneus.     

Neuropsychological assessment of cognitive function in chronic alcohol-dependent patients and patients with Alzheimer's disease

BACKGROUND: Heavy and chronic alcohol dependence and Alzheimer's disease may share some neuropsychological characteristics. PATIENTS AND METHODS: The pattern of neuropsychological characteristics of 33 alcohol-dependent patients who reported memory disturbances were evaluated and compared to the neuropsychological performance of 38 patients with mild-stage Alzheimer's disease and 73 healthy subjects, serving as controls. Alcohol-dependent patients were examined with tools concerning the pattern of alcohol abuse and problems related to alcohol consumption. All groups completed a full battery of neuropsychological tests for the assessment of cognitive functions, such as different kinds of memory, attention, executive function etc. RESULTS: Alcohol-dependent patients fared worse compared to the control subjects in every test used. The comparison of alcohol-dependent patients versus patients with Alzheimer's disease showed that the latter are much more burdened, as far as cognition is concerned, in all aspects of memory. CONCLUSION: Alcohol-dependent patients, even if they are not demented, have mild cognitive impairment in all domains of cognition (memory and frontal functions) in comparison with controls which performed within the norms. Verbal fluency, working memory and frontal functions were impaired at the same degree in alcohol-dependent patients and in patients with Alzheimer's disease. Memory problems were more pronounced in Alzheimer's disease patients.     

Cholinergic agonism alters cognitive processing and enhances brain functional connectivity in patients with multiple sclerosis

The aim of this study is to define mechanisms underlying the pharmacological effects of brain cholinesterase inhibition on cognitive function in patients with multiple sclerosis (MS). Both a Stroop task and an N-back task were used to probe the changes in brain activity using functional magnetic resonance imaging (fMRI) in a single (investigator)-blind, crossover treatment design studying 15 patients with multiple sclerosis (12 relapsing remitting, 3 secondary progressive) taking rivastigmine (4.5 mg po bid) and domperidone (10 mg po qd) or domperidone alone. Administration of rivastigmine increased Stroop functional magnetic resonance imaging activation in the right inferior frontal gyrus for the Stroop task (P < 0.05, corrected). Incremental functional magnetic resonance imaging activation with progressively greater N-back task difficulty was enhanced by rivastigmine in prefrontal and parietal cortical regions (P < 0.01, ANOVA). Functional connectivity analysis of the N-back functional magnetic resonance imaging data based on correlations between pair-wise interregional activations showed increased connectivity between left to right prefrontal, anterior cingulate to left prefrontal and right parietal to right prefrontal regions with rivastigmine (P < 0.05, corrected). Although there were no statistically significant changes in the neuropsychological task performance with rivastigmine in this small study, 11 of 15 patients showed improvements, whereas only 4 of 15 patients showed decline in performance (P = 0.07). With regard to the previous data, these findings suggest different patterns of brain response to lower dose acute and higher dose chronic administration of rivastigmine in patients with multiple sclerosis. They showed that rivastigmine enhances the prefrontal function and alters the functional connectivity associated with cognition. We interpret this as evidence for greater efficiency of brain information transfer that should increase confidence in a potentially beneficial clinical therapeutic effect.     

Limbic versus cognitive target for deep brain stimulation in treatment-resistant depression: Accumbens more promising than caudate

High-frequency deep brain stimulation (DBS) represents a major stake for treatment for treatment-resistant depression (TRD). We describe a preliminary trial of DBS of two potential brain targets in chronic TRD: the nucleus accumbens (Acb) and, in the event of failure, the caudate nucleus. Patients were followed for 6 months before surgery (M0). From M1 to M5, they underwent stimulation of the Acb target. PET scans allowed us to track metabolic modifications resulting from this stimulation. The caudate target of nonresponders was stimulated between M5 and M9. Patients then entered an extension phase, in which it was possible to adapt stimulation parameters and treatments. Six patients were included and four were operated on. At M5, none of the patients were either responders or remitters, but we did observe a decrease in Hamilton Depression Rating Scale (HDRS) scores. Three patients were switched to caudate stimulation, but no improvement was observed. During the extension phase, the Acb target was stimulated for all patients, three of whom exhibited a significant response. A decrease in glucose metabolism was observed after Acb stimulation, in the posterior cingulate gyrus, left frontal lobe, superior and medial gyrus, and bilateral cerebellum. An increase in metabolism was observed in the bilateral frontal lobe (superior gyrus), left frontal lobe (medial gyrus), and right limbic lobe (anterior cingulate gyrus). The results of this trial suggest that Acb is a more promising target than the caudate. NCT01569711.     

Measuring Cigarette Smoking-Induced Cortical Dopamine Release: A [11C]FLB-457 PET Study

Striatal dopamine (DA) is thought to have a fundamental role in the reinforcing effects of tobacco smoking and nicotine. Microdialysis studies indicate that nicotine also increases DA in extrastriatal brain areas, but much less is known about its role in addiction. High-affinity D_2/3 receptor radiotracers permit the measurement of cortical DA in humans using positron emission tomography (PET). [¹¹C]FLB-457 PET scans were conducted in 10 nicotine-dependent daily smokers after overnight abstinence and reinstatement of smoking. Voxel-wise [¹¹C]-FLB-457-binding potential (BP_ND) in the frontal lobe, insula, and limbic regions was estimated in the two conditions. Paired t-tests showed BP_ND values were reduced following smoking (an indirect index of DA release). The overall peak t was located in the cingulate gyrus, which was part of a larger medial cluster (BP_ND change −12.1±9.4%) and this survived false discovery rate correction for multiple comparisons. Clusters were also identified in the left anterior cingulate cortex/medial frontal gyrus, bilateral prefrontal cortex (PFC), bilateral amygdala, and the left insula. This is the first demonstration of tobacco smoking-induced cortical DA release in humans; it may be the result of both pharmacological (nicotine) and non-pharmacological factors (tobacco cues). Abstinence increased craving but had minimal cognitive effects, thus limiting correlation analyses. However, given that the cingulate cortex, PFC, insula, and amygdala are thought to have important roles in tobacco craving, cognition, and relapse, these associations warrant investigation in a larger sample. [¹¹C]FLB-457 PET imaging may represent a useful tool to investigate individual differences in tobacco addiction severity and treatment response.     

嗅觉障碍检测对轻度认知功能损害诊断价值的研究

目的探讨在中老年（50岁以上）人群中嗅觉障碍检测对轻度认知功能损害诊断的价值。方法运用简易智能状态检查（MMSE）对研究人群进行认知功能检查,根据MMSE结果将受试人群分为可能MCI组（n=19）和正常对照组（n=46）。采用气味感知阈试验、气味识别试验、气味再记忆试验等对受试者进行嗅觉功能检测。结果可能MCI组的气味感知阈值（P〈0.01）、气味识别（P〈0.01）和气味再记忆功能（P〈0.05）较正常对照组差;相关分析显示,MMSE总分与气味识别之间有显著的相关性（r=0.299,P〈0.05）。结论 MCI患者存在嗅觉功能损害,嗅觉障碍是MCI的简单反映;嗅觉的气味识别可以作为早期筛查认知功能损害的方法之一。