Cerebrospinal fluid biomarkers in Alzheimer’s disease, vascular dementia and ischemic stroke patients: a critical analysis

Vascular factors are thought to contribute to the development of disease pathology in neurodegenerative dementia such as Alzheimer’s disease (AD). Another entity, called vascular dementia (VaD), comprises a less defined group of dementia patients having various vascular diseases that especially emerge in the elderly population and require valid options for examination and differential diagnosis. In the context of a retrospective study, we analyzed the cerebrospinal fluid (CSF) biomarkers t-tau, p-tau and Aß42 of a total of 131 patients with AD (n = 47), mild cognitive impairment (MCI) (n = 22), VaD (n = 44) and stroke (n = 18). We found a remarkable alteration in CSF biomarker profile in AD, VaD and in acute ischemic events. CSF profile in AD patients was altered in a very similar way as in stroke patients, without statistical differences. In stroke, increase depend largely on size and duration after the initial event. Total tau levels were useful to differ between VaD and stroke. Aß42 decreased in a similar way in AD, VaD and stroke and had a trend to lower levels in MCI but not in controls.     

Combined Plasma Biomarkers for Diagnosing Mild Cognition Impairment and Alzheimer’s Disease

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皮质下缺血性脑血管病认知功能障碍研究

目的应用系列神经心理学测试分析皮质下缺血性脑血管病(SIVD)患者的认知损害特征。方法入选SIVD患者53例,年龄及性别相当的健康老年人25例为正常对照组。SIVD患者按照认知损害的诊断标准分为血管性痴呆(VaD)组27例和血管性认知障碍非痴呆(VCIND)组26例。进行MMSE及血管性痴呆包括记忆力、注意力、语言、视空间结构及执行功能5个认知域在内的神经心理学测试,确定VCIND患者受损的认知域。结果①与正常对照组比较,VaD组患者各项量表测试均严重受损,具有统计学差异(P﹤0.05);②VCIND组患者MMSE、数字倒背评分下降,连线测验时间延长,差异有统计学意义(P﹤0.05);③VaD组与VCIND组相比,上述各项均受损严重,其中单词回忆、连线测验、画钟测验、数字广度测验评分差异有统计学意义(P﹤0.05)。结论①SIVD患者同时存在多个认知域损害,以执行功能、注意力损害较为突出,记忆、语言受累相对较轻;②VCIND患者表现为执行功能、注意力受损,程度均低于VaD组,晚期VaD患者全面认知功能明显下降。     

Predictive accuracy of MCI subtypes for Alzheimer's disease and vascular dementia in subjects with mild cognitive impairment: a 2-year follow-up study

AIM: The aim of this study was to investigate the prognostic accuracy of different subtypes of mild cognitive impairment (MCI): amnestic MCI, multiple domain MCI, and single non-memory domain MCI, for the development of Alzheimer's dementia (AD) and vascular dementia (VaD). PATIENTS: Nondemented patients from a memory clinic cohort (n = 118), and a stroke cohort (n = 80, older than 55 years and with a cognitive impairment). RESULTS: 'Multiple domain MCI' had the highest sensitivity for both AD (80.8%) and VaD (100%), and 'amnestic MCI' had the highest specificity (85.9% for AD, 100% for VaD). The positive predictive value was low for all subtypes (0.0-32.7%), whereas the negative predictive value was high (72.8-100%). DISCUSSION: The subtype 'multiple domain MCI' has high sensitivity in identifying people at risk for developing AD or VaD. The predictive accuracy of the MCI subtypes was similar for both AD and VaD.     

Identification of VaD and AD prodromes: The Cache County Study

BackgroundIt is unclear whether vascular dementia (VaD) has a cognitive prodrome, akin to the mild cognitive impairment (MCI) prodrome to Alzheimer’s dementia (AD). To evaluate whether VaD has a cognitive prodrome, and if it can be differentiated from prodromal AD, we examined neuropsychological test performance of participants in a nested case-control study within a population-based cohort aged 65 or older.MethodsParticipants (n = 485) were identified from the Cache County Study, a large population-based study of aging and dementia. After an average of 3 years of follow-up, a total of 62 incident dementia cases were identified (14 VaD, 48 AD). We identified a number of neuropsychological tests (executive and memory) that discriminated between diagnosed VaD and AD cases. Multivariate analyses sought to differentiate between these same groups 3 years before clinical diagnosis.ResultsThe Consortium to Establish a Registry for Alzheimer’s Disease Word List Recognition Test correct recognition of foils (mean difference, 1.25; 95% confidence interval [CI], 0.42 to 2.07; p < 0.01), Logical Memory I (mean difference, 7.16; 95% CI, 0.78 to 13.55, p < 0.05), Logical Memory II delayed recall (mean difference, 8.67; 95% CI, 1.59 to 15.74, p < 0.05), and percent savings (mean difference, 51.07; 95% CI, 32.58 to 69.56, p < 0.0001) differentiated VaD from AD cases after adjustment for age, sex, education, and dementia severity. Three years before dementia diagnosis, word list recognition (“no” responses mean difference, 1.40; 95% CI, 0.64 to 2.17; p < 0.001, and “yes” responses mean difference, –1.14; 95% CI, –2.14 to –0.13; p < 0.03) discriminated between prodromal VaD and AD.ConclusionThese results suggest that VaD has a prodromal syndrome, the cognitive features of which are distinguishable from the cognitive prodrome of AD.     

Metabolic Syndrome,Mild Cognitive Impairment,and Dementia: A Meta-Analysis of Longitudinal Studies

ObjectiveA systematic review and a meta-analysis of both clinical and population-based studies was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to clarify whether Metabolic Syndrome (MetS) is a risk or a protective factor for incident dementia, Alzheimer disease (AD), and vascular dementia (VaD), and whether it's involved in progression to dementia in patients affected by mild cognitive impairment (MCI).MethodsSearch terms included (“metabolic syndrome” OR “syndrome x” OR “plurimetabolic syndrome”) AND (“dementia” OR “Alzheimer disease” OR “vascular dementia” OR “mild cognitive impairment” OR “MCI”). Research was restricted to articles published in English between January 1, 2000 and August 31, 2018. No age limit was set.ResultsAt the end of the selection procedure, nine longitudinal studies were selected for the meta-analysis: six studies enrolled cognitively well-functioning participants and three studies involved MCI patients. A total of 18,313 participants aged older than 40 years with mean MetS prevalence of 22.7% were followed on average for 9.41years. A fixed model was used to estimate pooled hazard ratios and 95% confidence intervals.ConclusionNo statistically significant pooled association emerged between MetS and incident dementia and AD. MetS increased the incidence of pure VaD. MetS increased the risk of progression from MCI to dementia. Follow-up length might be a key factor in investigating these associations further. Because MetS is constituted by a set of potentially modifiable factors, further studies with longer follow-up and repeated assessment of both MetS and cognitive status are desirable to draw definite conclusions.     

Enhanced cued recall and clock drawing test performances differ in Parkinson's and Alzheimer's disease-related cognitive dysfunction

Cognitive impairment either as dementia (PD–D) or mild cognitive impairment (PD–MCI) is common in Parkinson's disease (PD). The clinical features and cognitive profile differs from Alzheimer's disease (AD) or amnestic MCI (aMCI). In this study we aim to disclose the utility of pre-selected practical neuropsychological tests in differentiation of PD–D and AD, and also PD–MCI and aMCI. Consecutive cases with mild to moderate AD (n = 32) and PD–D (n = 26); aMCI (n = 34) and PD–MCI (n = 19) were evaluated. Although MMSE scores were similar in PD–D and AD or in PD–MCI and aMCI groups, memory impairment assessed by enhanced cued recall (ECR) was more apparent in AD than PD–D; and ECR scores tended to be worse in aMCI group than PD–MCI group. In contrast, clock drawing was more impaired in PD–D than AD. For differentiation of PD–D from AD, ECR, clock drawing and letter fluency were found to be valuable with moderately high sensitivity and specificities. In differentiation of aMCI and PD–MCI, ECR, clock drawing test and copying of intersecting pentagons were helpful. Stepwise linear discrimination function analysis disclosed that combination of ECR and clock drawing tests correctly classified 70.7% of the overall study population (71.4% of AD, 71.9% of aMCI, 69.6% of PD–D and 68.8% of PD–MCI). These findings suggest that ECR and clock drawing tests can be valuable as an additive to clinical diagnostic criteria in differentiation of PD–D and PD–MCI cases from AD and aMCI.     

Intracranial volume in mild cognitive impairment,Alzheimer's disease and vascular dementia: evidence for brain reserve?

OBJECTIVE: The possibility of brain volume reserve effects was examined in a sample of geriatric outpatients with mild cognitive impairment (MCI), Alzheimer's disease (AD) and vascular dementia (VaD). The total intracranial volume (ICV) served as an estimate of the maximum attained brain volume in life. METHODS: Subjects (n = 181, mean age 60.7) were consecutive referrals to a geriatric outpatients clinic (n = 96) and a group of age-matched healthy control subjects (n = 85). ICV and brain volume were attained from T1-weighted magnetic resonance images using a stereological method. Hippocampal atrophy was assessed with a visual rating scale. RESULTS: ICV was significantly smaller in patients with AD and VaD than in control subjects, but effect size was small. After adjusting for age and gender, having ICV in the smallest quartile significantly increased the risk of cognitive impairment (either MCI or dementia). In patients with dementia, but not in MCI, severity of cognitive impairment and ICV were moderately correlated. The effect of ICV on cognition was not mediated by hippocampal atrophy. CONCLUSIONS: These findings are compatible with volume reserve effects that modify the clinical expression of symptoms in both AD and VaD. They may have implications for the design of neuroimaging studies that use ICV for normalization procedures.     

Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer’s disease

Background and purpose: Life style‐related disorders such as hypertension, diabetes, dyslipidemia, and obesity are reported to be a great risk of dementia. Adipocytokines released from adipose tissue are thought to modulate some brain functions including memory and cognition. We here analysed adiponectin, one of the most important adipocytokines, in plasma and cerebrospinal fluid (CSF) from cognitive normal controls (NC), mild cognitive impairment (MCI) subjects, and patients with Alzheimer’s disease (AD) and discussed if/how adiponectin could relate to the pathogenesis of AD. Methods: Normal controls (n = 28), MCI (n = 18), and AD (n = 27) subjects were recruited at Tohoku University Hospital. The diagnosis of AD was based on NINCDS‐ADRDA criteria. All the blood and CSF samples were obtained from each fasted subject. Adiponectin was assayed using a sandwich ELISA system. Results: The levels of adiponectin between in plasma and in CSF showed a positive correlation. Plasma adiponectin was significantly higher in MCI and AD compared to NC, whereas CSF adiponectin was significantly higher in MCI compared to NC. Conclusion: It is possible that the level of adiponectin in plasma reflects its level in CSF. The tendency to have higher adiponectin in plasma and CSF from MCI and AD suggests that this molecule plays a critical role in the onset of AD.     

Apolipoprotein E phenotypes in demented and cognitively impaired patients with and without cerebrovascular disease

Controversy exists regarding the apolipoprotein E (ApoE) epsilon4 allele association with vascular dementia (VaD), ranging from increased epsilon4 frequency, similar to that found for Alzheimer's disease (AD), to no association between the epsilon4 allele and VaD. To clarify further the relationship between ApoE alleles polymorphism and cerebrovascular disease (CVD) in demented and cognitively impaired patients, we examined the ApoE phenotypes in a sample of 280 patients: 155 with AD, 21 with VaD, 32 with mixed dementia (MD), 45 with mild cognitive impairment (MCI) but without CVD, and 27 in which vascular disease was the most probable cause of cognitive decline [vascular mild cognitive impairment (VMCI)]. Our results show that the frequency of the ApoE epsilon4 allele in patients over 70 years old with clinically diagnosed VaD and VMCI does not differ significantly from that of controls. In contrast, ApoE epsilon4 allele-bearing individuals had greater risk of having late-onset AD (OR = 8.8; 95% CI 3.7-21.0), or non-vascular cognitive impairment (OR = 7.0; 95% CI 2.5-19.0).     

Discrepancy of subjective and objective sleep problems in Alzheimer’s disease and mild cognitive impairment detected by a home-based sleep analysis

There is a strong relationship between Alzheimer’s disease (AD) and sleep problems, and a sleep condition is informative for evaluating the AD status. In the present study, we evaluated subjective sleep problems in AD and mild cognitive impairment (MCI) with self-check questionnaires and objective sleep problems with a convenient home-based portable device, WatchPAT. A total of 63 subjects with normal cognition (NC) (n = 22), MCI (n = 20), and AD (n = 21) were cross-sectionally investigated. AD patients showed a better self-check Pittsburgh sleep quality index (PSQI) score (*p < 0.05) than NC and MCI patients. On the other hand, WatchPAT analysis showed a significantly reduced rapid eye movement (REM) sleep (*p < 0.05) and increased light sleep in AD patients (*p < 0.05) compared with NC subjects, and mildly reduced REM and increased light sleep in MCI subjects. The present study revealed a gap between the subjective self-check sleep questions and the objective WatchPAT analysis in AD patients. Thus, a home-based sleep study with WatchPAT is a useful tool to detect an objective sleep problem in AD and the risk of MCI conversion into AD.     

Cognition in MCI and Alzheimer’s Disease: Baseline Data from a Longitudinal Study of the NTB

Baseline data are summarized from a study examining the psychometric properties of the Neuropsychological Test Battery (NTB) and its subtests, and correlating the NTB with other cognitive and functional assessments. A multicenter, longitudinal, non-interventional study included mild to moderate Alzheimer’s disease (AD, n = 196), mild cognitive impairment (MCI, n = 70), or normal cognition participants (NC, n = 75). The NTB, other cognitive assessment tools, functional/behavioral questionnaires, and health outcome assessments were administered. At baseline composite NTB, NTB memory, and NTB executive function z-scores were significantly lower for participants with AD compared with MCI, and for participants with MCI compared with NC. The composite NTB z-score had high test–retest reliability between screening and baseline. The results of this study suggest that NTB exhibits good reliability in patients with mild to moderate AD and MCI.     

Is there any relation between insulin resistance and cognitive function in the elderly?

BACKGROUND: Vascular risk factors are blamed as being involved in the pathogenesis of cognitive dysfunction in the elderly. Alzheimer's disease or vascular-type dementia could be part of a metabolic syndrome. The aim of this study was to evaluate whether there is any relation between insulin resistance and cognitive status of the elderly regarding normal, mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia.METHODS: 267 elderly patients admitted to an outpatient geriatrics clinic were evaluated medically and cognitively in this study. The patients were diagnosed using ARDRA and DSM-IV criteria for AD; NINDS-AIREN and DSM-IV criteria for VaD; and Petersen criteria for MCI. Insulin resistance was calculated using both the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) formulas.RESULTS: The mean values of HOMA and QUICKI scores were 2.79 (SD+/-3.56) and 0.346 (SD+/-0.036) for the normal group, 2.81 (SD+/-3.06) and 0.354 (SD+/-0.047) for AD group, 2.20 (SD+/-1.82) and 0.360 (SD+/-0.048) for VaD group, 2.87 (SD+/-1.81) and 0.339 (SD+/-0.038) for mixed dementia group, 2.79 (SD+/-2.81) and 0,349 (SD+/-0.042) for MCI group, respectively. There were no statistically significant differences between HOMA and QUICKI scores of all the groups.CONCLUSION: This is the first study of the possible relation between insulin resistance and cognitive function in people categorized according to five forms of cognitive status. Unfortunately the results do not allow generalizations. Further prospective cohort studies that follow a normal cognitive group and MCI patients with and without insulin resistance are necessary.     

Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions.Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.     

以精神行为异常为主要症状的非痴呆型血管性认知障碍临床研究

目的 分析以精神行为异常为主要症状的非痴呆型血管认知障碍（vascular cognitive impairment no
dementia,VCIND）的精神行为特点和认知功能特征。
方法 本研究为横断面研究,收集2011年6月～2013年12月广州市脑科医院以精神行为异常为主要
症状就诊的VCIND18例、伴有精神行为异常的血管性痴呆（vascular dementia,VaD）16例和无认知功能
障碍（no cognitive impairment,NCI）18例作为对照组。采用神经精神科问卷（Neuropsychiatric Inventory,
NPI）和简易精神状态检查量表（Mini-Mental State Examination,MMSE）及蒙特利尔认知评估量表
（Montreal Cognitive Assessment,MoCA）分别评定精神行为和认知状态,并比较各组间精神行为及认
知状态的差异。
结果 VCIND组最多见的精神行为异常表现为易激惹/情绪不稳（66.7%）,睡眠障碍（61.1%）,其
次为激越/攻击行为（55.6%）,幻觉/妄想（44.4%）。VaD组焦虑/抑郁症状与VCIND组相比较多见,差
异具有显著性（75% vs 16.7%;P =0.001）。VCIND组各认知评分介于VaD组和NCI组之间,与NCI组
相比,在视空间/执行能力（2.78±0.73 vs 4.50±0.51）、注意（4.61±0.61 vs 5.33±0.48）、语言
（2.11±0.47 vs 2.67±0.49）、抽象［1（0,1）vs 2（1,2）］、延迟记忆［2（2,3）vs 4（4,4）］方面差异
均具有显著性（P <0.001）。
结论 VCIND可以以精神行为异常为主要表现,尤其是急起的易激惹/情绪不稳、睡眠障碍及激越/
攻击行为。     

Yes/No Versus Forced-Choice Recognition Memory in Mild Cognitive Impairment and Alzheimer's Disease: Patterns of Impairment and Associations with Dementia Severity

Memory tests are sensitive to early identification of Alzheimer's disease (AD) but less useful as the disease advances. However, assessing particular types of recognition memory may better characterize dementia severity in later stages of AD. We sought to examine patterns of recognition memory deficits in individuals with AD and mild cognitive impairment (MCI). Memory performance and global cognition data were collected from participants with AD (n?=?37), MCI (n?=?37), and cognitively intact older adults (normal controls, NC; n?=?35). One-way analyses of variance (ANOVAs) examined differences between groups on yes/no and forced-choice recognition measures. Individuals with amnestic MCI performed worse than NC and nonamnestic MCI participants on yes/no recognition, but were comparable on forced-choice recognition. AD patients were more impaired across yes/no and forced-choice recognition tasks. Individuals with mild AD (≥120 Dementia Rating Scale, DRS) performed better than those with moderate-to-severe AD (<120 DRS) on forced-choice recognition, but were equally impaired on yes/no recognition. There were differences in the relationships between learning, recall, and recognition performance across groups. Although yes/no recognition testing may be sensitive to MCI, forced-choice procedures may provide utility in assessing severity of anterograde amnesia in later stages of AD. Implications for assessment of insufficient effort and malingering are also discussed.     

急性缺血性卒中患者血管性认知障碍及其亚型的相关因素分析

目的探讨急性缺血性卒中患者血管性认知障碍(vascular cognitive impairment,VCI)及其亚型非痴呆性血管性认知障碍(VCI-no dementia,VCIND)与血管性痴呆(vascular dementia,Va D)发生的主要相关因素。方法选择2014年6月至2015年6月就诊于天津医科大学总医院神经内科的491例急性缺血性卒中患者为研究对象,应用前期已建立的血管性认知障碍数据库记录患者的一般人口学信息、病史、体格检查、血管危险因素、生化及影像检查信息,对患者进行美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分、Essen评分及低分子肝素治疗急性卒中试验(the Trial of Org 10172 in Acute Stroke Treatment,TOAST)分型,于发病(10±2)d进行蒙特利尔认知量表(Montreal Cognitive Assessment,Mo CA)、临床痴呆量表(Clinical Dementia Rating,CDR)、日常生活能力量表(Activities of Daily Living,ADL)评分,依据血管性认知障碍诊治指南中VCI的诊断及分类诊断标准将患者分为认知正常组(no cognitive impairment,NCI)和VCI组,VCI组包括VCIND组和Va D组,分析上述各项因素的组间差异及相关性。结果 491例急性缺血性卒中患者中VCI占69.86%,其中包括37.68%的VCIND和32.18%的Va D患者。1VCI组低受教育程度(P0.001)、糖尿病(P=0.005)、心脏病(P=0.045)、卒中家族史(P=0.005)、幕上病变(P0.001)的比例及卒中次数(P=0.014)、D-二聚体水平(P=0.001)、Essen评分(P=0.024)、NIHSS评分(P0.001)显著高于NCI组,女性(P=0.004)、幕下病变(P0.001)的比例及受教育年(P0.001)显著低于NCI组,差异均有显著性;Logistic回归分析显示低受教育程度、糖尿病、幕上病变和高D-二聚体水平是VCI的独立危险因素。2与VCIND组比较,Va D组患者既往卒中史(P=0.013)、TOAST分型中大动脉粥样硬化型梗死(P0.001)的比例及卒中次数(P=0.001)、Essen评分(P=0.032)、神经功能缺损程度(P=0.005)显著高于VCIND组,TOAST分型中小动脉闭塞型梗死(P0.001)、幕下病变(P0.001)的比例显著低于VCIND组,差异均有显著性;Logistic回归分析显示卒中次数、神经功能缺损程度、大动脉粥样硬化型梗死是Va D的独立危险因素,而幕下病变患者发生Va D的风险明显小于幕上病变患者。结论 VCI及其亚型的影响因素不同,与NCI比较,低受教育程度、糖尿病、幕上病变和高D-二聚体水平是VCI的独立危险因素;与VCIND比较,卒中次数、严重的神经功能缺损、TOAST分型中大动脉粥样硬化型梗死是Va D的独立危险因素。     

Expression of inducible nitric oxide synthase (iNOS) and period 1 (PER1) clock gene products in different sleep stages of patients with cognitive impairment

Circadian and sleep disturbances are common behavioural and psychological symptoms of dementia; circadian rhythm–related molecules may be altered in dementia patients. This study investigated the expression of the period 1 clock gene product (PER1), which is involved in circadian rhythms, and inducible nitric oxide synthase (iNOS), thought to generate nitric oxide, important in rapid eye movement (REM) sleep regulation. Specifically, we investigated the difference in expression of these two genes between patients with cognitive impairment and controls. We studied iNOS and PER1 mRNA expression using real-time polymerase chain reaction in peripheral leukocytes during REM sleep, non-REM sleep and wake stages in patients with Alzheimer’s disease (AD, n = 5), patients with mild cognitive impairment (MCI, n = 8) and controls (n = 9) during polysomnography examination. Expression of iNOS significantly increased during REM sleep in AD patients compared to MCI patients and controls. There were no significant differences in PER1 expression between the three groups, but an increase in PER1 expression during the wake stage was observed for all participants. Increased expression of iNOS during REM sleep of patients with AD might be a compensation mechanism for maintaining REM sleep. However, the precise role of nocturnal expression of iNOS in patients with AD requires further investigation.     

皮质下缺血性血管性认知损害扩散张量成像研究

目的通过扩散张量成像(DTI)探讨皮质下缺血性血管性认知损害患者白质微结构变化及其与认知功能之间的相关性。方法采集49例皮质下缺血性脑血管病患者[轻度血管性痴呆(VaD)10例、非痴呆型血管性认知损害(VCIND)20例、认知功能正常19例]DTI数据并观察皮质下白质微结构改变,分析VaD组患者DTI参数与认知功能间的相关性。结果与对照组相比,VaD组内侧前额叶、前扣带回、胼胝体干、双侧顶叶、右侧颞叶、双侧眶额叶,以及VCIND组右侧额下回、右侧海马、双侧楔前叶FA值减低(均P=0.000);与VCIND组比较,VaD组内侧前额叶、前扣带回、胼胝体、双侧顶叶、右侧颞叶FA值减低(P=0.000)。与对照组相比,VaD组内侧前额叶、胼胝体、双侧顶叶、双侧颞叶、前扣带回,以及VCIND组双侧楔前叶、右侧海马MD值升高(均P=0.000);与VCIND组相比,VaD组右侧内侧前额叶、前扣带回、胼胝体干、双侧顶叶、双侧颞叶MD值升高(均P=0.000)。VaD组内侧前额叶FA值与数字连线测验A时呈显著负相关(r=-0.782,P=0.007),双侧额下回MD值与数字连线试验A时程呈显著正相关(r=0.877,P=0.001)。结论 DTI对皮质下缺血性认知损害患者白质微结构改变更敏感,能够反映患者认知功能早期异常改变;内侧前额叶白质微结构的改变是影响患者执行能力的重要因素。     

Regional hyperperfusion in older adults with objectively-defined subtle cognitive decline

Although cerebral blood flow (CBF) alterations are associated with Alzheimer’s disease (AD), CBF patterns across prodromal stages of AD remain unclear. Therefore, we investigated patterns of regional CBF in 162 Alzheimer’s Disease Neuroimaging Initiative participants characterized as cognitively unimpaired (CU; n = 80), objectively-defined subtle cognitive decline (Obj-SCD; n = 31), or mild cognitive impairment (MCI; n = 51). Arterial spin labeling MRI quantified regional CBF in a priori regions of interest: hippocampus, inferior temporal gyrus, inferior parietal lobe, medial orbitofrontal cortex, and rostral middle frontal gyrus. Obj-SCD participants had increased hippocampal and inferior parietal CBF relative to CU and MCI participants and increased inferior temporal CBF relative to MCI participants. CU and MCI groups did not differ in hippocampal or inferior parietal CBF, but CU participants had increased inferior temporal CBF relative to MCI participants. There were no CBF group differences in the two frontal regions. Thus, we found an inverted-U pattern of CBF signal across prodromal AD stages in regions susceptible to early AD pathology. Hippocampal and inferior parietal hyperperfusion in Obj-SCD may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain cognitive functioning relative to MCI participants, yet is also reflective of early cognitive inefficiencies that distinguish Obj-SCD from CU participants.