Estimating High-Order Functional Connectivity Networks for Mild Cognitive Impairment Identification Based on Topological Structure

Functional connectivity networks (FCNs) are important in the diagnosis of neurological diseases and the understanding of brain tissue patterns. Recently, many methods, such as Pearson’s correlation (PC), Sparse representation (SR), and Sparse low-rank representation have been proposed to estimate FCNs. Despite their popularity, they only capture the low-order connections of the brain regions, failing to encode more complex relationships (i.e. , high-order relationships). Although researchers have proposed high-order methods, like PC + PC and SR + SR, aiming to build FCNs that can reflect more real state of the brain. However, such methods only consider the relationships between brain regions during the FCN construction process, neglecting the potential shared topological structure information between FCNs of different subjects. In addition, the low-order relationships are always neglected during the construction of high-order FCNs. To address these issues, in this paper we proposed a novel method, namely Ho-FCNTops, towards estimating high-order FCNs based on brain topological structure. Specifically, inspired by the Group-constrained sparse representation (GSR), we first introduced a prior assumption that all subjects share the same topological structure in the construction of the low-order FCNs. Subsequently, we employed the Correlation-reserved embedding (COPE) to eliminate noise and redundancy from the low-order FCNs. Meanwhile, we retained the original low-order relationships during the embedding process to obtain new node representations. Finally, we utilized the SR method on the obtained new node representations to construct the Ho-FCNTops required for disease identification. To validate the effectiveness of the proposed method, experiments were conducted on 137 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to identify Mild Cognitive Impairment (MCI) patients from the normal controls. The experimental results demonstrate superior performance compared to baseline methods.

Proteomics of serum exosomes identified fibulin-1 as a novel biomarker for mild cognitive impairment

Mild cognitive impairment(MCI)is a prodrome of Alzheimer’s disease pathology.Cognitive impairment patients often have a delayed diagnosis because there are no early symptoms or conventional diagnostic methods.Exosomes play a vital role in cell-to-cell communications and can act as promising biomarkers in diagnosing diseases.This study was designed to identify serum exosomal candidate proteins that may play roles in diagnosing MCI.Mass spectrometry coupled with tandem mass tag approach-based non-targeted proteomics was used to show the differentially expressed proteins in exosomes between MCI patients and healthy controls,and these differential proteins were validated using immunoblot and enzyme-linked immunosorbent assays.Correlation of cognitive performance with the serum exosomal protein level was determined.Nanoparticle tracking analysis suggested that there was a higher serum exosome concentration and smaller exosome diameter in individuals with MCI compared with healthy controls.We identified 69 exosomal proteins that were differentially expressed between MCI patients and healthy controls using mass spectrometry analysis.Thirty-nine exosomal proteins were upregulated in MCI patients compared with those in control patients.Exosomal fibulin-1,with an area under the curve value of 0.81,may be a biomarker for an MCI diagnosis.The exosomal protein signature from MCI patients reflected the cell adhesion molecule category.In particular,higher exosomal fibulin-1 levels correlated with lower cognitive performance.Thus,this study revealed that exosomal fibulin-1 is a promising biomarker for diagnosing MCI.

Brain Functional Networks with Dynamic Hypergraph Manifold Regularization for Classification of End-Stage Renal Disease Associated with Mild Cognitive Impairment

The structure and function of brain networks have been altered in patients with end-stage renal disease(ESRD).Manifold regularization(MR)only considers the pairing relationship between two brain regions and cannot represent functional interactions or higher-order relationships between multiple brain regions.To solve this issue,we developed a method to construct a dynamic brain functional network(DBFN)based on dynamic hypergraph MR(DHMR)and applied it to the classification of ESRD associated with mild cognitive impairment(ESRDaMCI).The construction of DBFN with Pearson’s correlation(PC)was transformed into an optimization model.Node convolution and hyperedge convolution superposition were adopted to dynamically modify the hypergraph structure,and then got the dynamic hypergraph to form the manifold regular terms of the dynamic hypergraph.The DHMR and L_(1) norm regularization were introduced into the PC-based optimization model to obtain the final DHMR-based DBFN(DDBFN).Experiment results demonstrated the validity of the DDBFN method by comparing the classification results with several related brain functional network construction methods.Our work not only improves better classification performance but also reveals the discriminative regions of ESRDaMCI,providing a reference for clinical research and auxiliary diagnosis of concomitant cognitive impairments.

Receded near point of convergence as a predictor of mild cognitive impairment in the general geriatric population:results from a population-based study

AIM:To investigate the relationship between near point of convergence(NPC)and mild cognitive impairment(MCI)in the general elderly population.METHODS:The present report is a part of the Tehran Geriatric Eye Study(TGES):a population-based crosssectional study conducted on individuals 60 years of age and above living in Tehran,Iran using the multi-stage stratified random cluster sampling method.Cognitive status was assessed using the Persian version of the Mini-Mental State Examination(MMSE).All study participants underwent complete ocular examination including measurement of uncorrected and best-corrected visual acuity,objective and subjective refraction,cover testing,NPC measurement,and slit-lamp biomicroscopy.RESULTS:The data of 1190 individuals were analyzed for this report.The mean age of the participants analyzed was 66.82±5.42(60-92y)and 728(61.2%)of them were female.Patients with MCI had a significantly more receded NPC compared to subjects with normal cognitive status(10.89±3.58 vs 7.76±2.71 cm,P<0.001).In the multivariable logistic regression model and in the presence of confounding variables,a receded NPC was statistically significantly associated with an increased risk of MCI(odds ratio:1.334,95%confidence interval:1.263 to 1.410,P<0.001).According to receiver operating characteristic(ROC)analysis,a cut point NPC>8.5 cm(area under the curve:0.764,P<0.001)could predict the presence of MCI with a sensitivity and specificity of 70.9%and 69.5%,respectively.CONCLUSION:A receded NPC can be clinically proposed as a predictor of MCI in older adults.It is recommended that elderly with a receded NPC>8.50 cm undergo detailed cognitive screening for a definite diagnosis of MCI.In this case,the necessary interventions can be carried out to slow down MCI progression to dementia.

The Effect of Sleep and Cognition Enhancement Multimodal Intervention for Mild Cognitive Impairment with Sleep Disturbance in the Community-Dwelling Elderly

Dementia prevalence has soared due to population aging. In Mild Cognitive Impairment (MCI) as a pre-dementia stage, sleepdisturbances have raised much interest as a factor in a bidirectional relationship with cognitive decline. Thus, this studydeveloped the Sleep and Cognition Enhancement Multimodal Intervention (SCEMI) based on Lazarus’ multimodal approachand conducted a randomized controlled experiment to investigate the effects of the novel program on sleep and cognition inMCI elderly. The participants were 55 MCI elderly with sleep disturbances at two dementia care centers located in S-city,Gyeonggi-do, South Korea (n = 25 in the experimental group and n = 30 in the control group). The study period was fromNovember 01 to December 27, 2022. The experimental group received 8 sessions of SCEMI, 60 min per session once a week.The control group received general education and guidance using a simplified booklet on the sleep and cognitive improvement.For data collection, a self-reported questionnaire was used to investigate sleep quality, presleep arousal, cognitive function,stress, and depression. The results showed that, compared to the control group, the experimental group had significantlyimproved across all variables: sleep quality (U = 109.50, p < 0.001), presleep arousal (U = 11.50, p < 0.001), cognitive function(U = 72.00, p < 0.001), stress (U = 139.00, p < 0.001), and depression (U = 231.50, p = 0.015). Thus, the SCEMI appears topositively affect symptomatic improvement and delays the progression to dementia as an integrated intervention to enhancesleep and cognition in community-dwelling MCI elderly with sleep disturbances.

A Novel Computerized Cognitive Test for the Detection of Mild Cognitive Impairment and Its Association with Neurodegeneration in Alzheimer’s Disease Prone Brain Regions

During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU;36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.

Acupuncture enhances brain function in patients with mild cognitive impairment: evidence from a functional-near infrared spectroscopy study

Mild cognitive impairment(MCI)is a precursor to Alzheimer’s disease.It is imperative to develop a proper treatment for this neurological disease in the aging society.This observational study investigated the effects of acupuncture therapy on MCI patients.Eleven healthy individuals and eleven MCI patients were recruited for this study.Oxy-and deoxy-hemoglobin signals in the prefrontal cortex during working-memory tasks were monitored using functional near-infrared spectroscopy.Before acupuncture treatment,working-memory experiments were conducted for healthy control(HC)and MCI groups(MCI-0),followed by 24 sessions of acupuncture for the MCI group.The acupuncture sessions were initially carried out for 6 weeks(two sessions per week),after which experiments were performed again on the MCI group(MCI-1).This was followed by another set of acupuncture sessions that also lasted for 6 weeks,after which the experiments were repeated on the MCI group(MCI-2).Statistical analyses of the signals and classifications based on activation maps as well as temporal features were performed.The highest classification accuracies obtained using binary connectivity maps were 85.7%HC vs.MCI-0,69.5%HC vs.MCI-1,and 61.69%HC vs.MCI-2.The classification accuracies using the temporal features mean from 5 seconds to 28 seconds and maximum(i.e,max(5:28 seconds))values were 60.6%HC vs.MCI-0,56.9%HC vs.MCI-1,and 56.4%HC vs.MCI-2.The results reveal that there was a change in the temporal characteristics of the hemodynamic response of MCI patients due to acupuncture.This was reflected by a reduction in the classification accuracy after the therapy,indicating that the patients’brain responses improved and became comparable to those of healthy subjects.A similar trend was reflected in the classification using the image feature.These results indicate that acupuncture can be used for the treatment of MCI patients.

Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong（EX-HN1）, Yintang（EX-HN3）, Neiguan（PC6）, Taixi（KI3）, Fenglong（ST40）, and Taichong（LR3）, or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.

Brain imaging of mild cognitive impairment and Alzheimer's disease

The rapidly increasing prevalence of cognitive impairment and Alzheimer＇s disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer＇s disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and AIzheimer＇s disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer＇s disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer＇s disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.

Individual identification using multi-metric of DTI in Alzheimer's disease and mild cognitive impairment

Accurate identification of Alzheimer＇s disease （AD） and mild cognitive impairment （MCI） is crucial so as to improve diagnosis techniques and to better understand the neurodegenerative process. In this work, we aim to apply the machine learning method to individual identification and identify the discriminate features associated with AD and MCI. Diffusion tensor imaging scans of 48 patients with AD, 39 patients with late MCI, 75 patients with early MCI, and 51 age-matched healthy controls （HCs） are acquired from the Alzheimer＇s Disease Neuroimaging Initiative database. In addition to the common fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity metrics, there are two novel metrics, named local diffusion homogeneity that used Spearman＇s rank correlation coefficient and Kendall＇s coefficient concordance, which are taken as classification metrics. The recursive feature elimination method for support vector machine （SVM） and logistic regression （LR） combined with leave-one-out cross validation are applied to determine the optimal feature dimensions. Then the SVM and LR methods perform the classification process and compare the classification performance. The results show that not only can the multi-type combined metrics obtain higher accuracy than the single metric, but also the SVM classifier with multi-type combined metrics has better classification performance than the LR classifier. Statistically, the average accuracy of the combined metric is more than 92% for all between-group comparisons of SVM classifier. In addition to the high recognition rate, significant differences are found in the statistical analysis of cognitive scores between groups. We further execute the permutation test, receiver operating characteristic curves, and area under the curve to validate the robustness of the classifiers, and indicate that the SVM classifier is more stable and efficient than the LR classifier. Finally, the uncinated fasciculus, cingulum, corpus callosum, corona radiate, external capsule, and internal capsule have been regarded as the most important white matter tracts to identify AD, MCI, and HC. Our findings reveal a guidance role for machine-learning based image analysis on clinical diagnosis.

Cognitive Training in Older Adults with Mild Cognitive Impairment

Objective We investigated the feasibility and efficacy of cognitive training for older adults in rura settings and with low education levels, who have mild cognitive impairment （MCl）. Methods Forty-five older adults （ages 〉65 years） with MCI were assigned to treatment or control groups, at a 2：1 ratio. Cognitive training occurred in the treatment group for 2 months. The cognitive abilities of the participants were assessed at pre-training, metaphase, and post-training time points, using the Mini-Mental State Examination （MMSE）, Montreal Cognitive Assessment （MoCA）, Loewenstein Occupational Therapy Cognitive Assessment （LOTCA）, and Hamilton Depression Scale （HAM-D）. Results Following training, cognitive abilities improved in the treatment group, based on the total scores of all 4 measures, as well as specifically on the MoCA and LOTCA. There were differences in the main effects of group and time point on some subscales, but these differences had little, if any, effect on the overall analyses. Conclusion The present study demonstrated that cognitive training has beneficial effects on attention, language, orientation, visual perception, organization of visual movement, and logical questioning in patients with MCI. Furthermore, the observed effects are long-term changes.

Bibliometric analysis of papers on mild cognitive impairment nursing in China

Purpose: To supply further references by analyzing the status of research on mild cognitive impairment nursing in China.Methods: Papers on mild cognitive impairment nursing published between 2005 and 2014 were collected from China National Knowledge Infrastructure,Wanfang Data,and China Biological Medicine database,while their publication dates,journals,and types were subjected to a bibliometric analysis using NoteExpress and Excel.Results: A total of 68 papers were collected from the selected databases.The number of papers on mild cognitive impairment nursing increased annually.The selected papers were published in 44 journals,55.88% of them were published in core journals,35.29% received funding support,35.29% were published by hospitals affiliated to colleges,47.06% were published by other local hospitals,author collaboration is 2.66,and 66.18% showed co-authorship.These papers covered a wide range of topics,but were only conducted based on clinical interventions.Around 29.41% of these papers had a citation frequency of over 5,the highest citation frequency was 29,and the highest h-index was 23.Conclusion: Beijing and Shanghai established core author groups for mild cognitive impairment nursing research.These studies should focus on the community and psychological nursing of such impairment.Targeted nursing interventions on different types of mild cognitive impairment should be adopted,new avenues for research should be opened,and various research methods should be introduced.

Improving wellbeing of community-dwelling people with mild cognitive impairment: the SENIOR (SystEm of Nudge theory based ICT applications for OldeR citizens) project

Population aging with longer life expectancy represents one of the most relevant challenges of the next future,also because of a significant proportion of older adult people may present with dementia.Motivating senior citizens with mild cognitive impairment to maintain their independence and functional abilities,improve health status and quality of life as well as social interactions,constitutes the main target of preventive medicine.According to a nudge theoretical approach,the SENIOR(SystEm of Nudge theory based ICT applications for OldeR citizens)project–developed thanks to the collaboration among Catholic University of the Sacred Heart,Bicocca University and IRCCS Auxiologico Institute in Milan(Italy)–has been designed to adopt an advanced information and communication technology coaching system able to collect and integrate physiological,psychological and behavioral data,with the final aim of interacting with community-dwelling elderly people suffering from mild cognitive impairment and of providing them personalized feedback on lifestyle management.The SENIOR project proposes to use a smart-watch app for alerting family doctors,sharing information with family members in specific cases and monitoring patients at higher risk in hospital Units,in order to ameliorate health of senior citizens with mild cognitive impairment.

Psychophysiological Effects of Sideritis and Bacopa Extract and Three Combinations Thereof—A Quantitative EEG Study in Subjects Suffering from Mild Cognitive Impairment (MCI)

Mild cognitive impairment (MCI) is regarded as a transitional stage during the development of Alzheimer’s disease. Diagnosis of MCI can be obtained by the questionnaire “DemTect” in German speaking countries. Quantitative assessment has been successfully performed using psychometric testing concomitantly with quantitative EEG recording. The present investigation aimed at the possible treatment of MCI with two botanicals, namely extracts from Sideritis scardica (500 mg) or Bacopa monnieri (320 mg) and three combinations thereof using this method in order to find a new treatment. The performance of the d2-test, an arithmetic calculation test (CPT) and a memory-test revealed better performance for the d2-test only in the presence of Sideritis extract or the combinations with Bacopa extract. Quantitative EEG assessment during the different experimental conditions showed massive differences between both extracts. Whereas Sideritis extract and its combination with a low amount of Bacopa extract (160 mg) induced increases of spectral power in fronto-temporal brain areas, Bacopa and the combination of Sideritis with high amounts of Bacopa extract produced attenuation of all waves except for delta in fronto-temporal brain areas. These differences were also documented by quantitative EEG maps in comparison to Placebo. A different action of both extracts was confirmed by discriminant analysis, where Sideritis extract and its combination with low Bacopa grouped together quite at distance to Bacopa and the combination of Sideritis with high Bacopa. A combination of Sideritis extract with a low amount of Bacopa should be tested with daily repetitive dosing for at least 4 weeks as a consequence.

Association of chronic obstructive pulmonary disease with mild cognitive impairment and dementia risk:A systematic review and meta-analysis

BACKGROUND Chronic obstructive pulmonary disease(COPD)is a common public health issue that has been linked to cognitive dysfunction.AIM To investigate the relationship between COPD and a risk of mild cognitive impairment(MCI)and dementia.METHODS A comprehensive literature search of the PubMed,Embase,Google Scholar,and Cochrane Library electronic databases was conducted.Pooled odds ratios(OR)and mean differences(MD)with 95%confidence intervals(CIs)were calculated using a random or fixed effects model.Studies that met the inclusion criteria were assessed for quality using the Newcastle Ottawa Scale.RESULTS Twenty-seven studies met all the inclusion criteria.Meta-analysis yielded a strong association between COPD and increased risk of MCI incidence(OR=2.11,95%CI:1.32-3.38).It also revealed a borderline trend for an increased dementia risk in COPD patients(OR=1.16,95%CI:0.98-1.37).Pooled hazard ratios(HR)using adjusted confounders also showed a higher incidence of MCI(HR=1.22,95%CI:-1.18 to-1.27)and dementia(HR=1.32,95%CI:-1.22 to-1.43)in COPD patients.A significant lower mini-mental state examination score in COPD patients was noted(MD=-1.68,95%CI:-2.66 to-0.71).CONCLUSION Our findings revealed an elevated risk for the occurrence of MCI and dementia in COPD patients.Proper clinical management and attention are required to prevent and control MCI and dementia incidence in COPD patients.

Usefulness of the Japanese version of Rapid Dementia Screening Test for mild cognitive impairment in older patients with cardiovascular disease:a cross-sectional study

BACKGROUND Cognitive decline is common among older patients with cardiovascular disease(CVD) and can decrease their self-management abilities. However, the instruments for identifying mild cognitive impairment(MCI) are not always feasible in clinical practice. Therefore, this study evaluated whether MCI could be detected using the Japanese version of the Rapid Dementia Screening Test(RDST-J), which is a simple screening tool for identifying cognitive decline.METHODS This retrospective single-center study included patients who were ≥ 65 years old and hospitalized because of CVD.Patients with a pre-hospitalization diagnosis of dementia were excluded. Each patient's cognitive function had been measured at discharge using the RDST-J and the Japanese version of the Montreal Cognitive Assessment(Mo CA-J), which is a standard tool for MCI screening. The correlation between the two scores was evaluated using Spearman's rank correlation coefficient. Receiver operating characteristic(ROC) analysis was also to evaluate whether the RDST-J could identify MCI, which was defined as a Mo CA-J score of ≤ 25 points.RESULTS The study included 78 patients(mean age: 77.2 ± 8.9 years). The RDST-J and Mo CA-J scores were strongly correlated(r = 0.835, P < 0.001). The ROC analysis revealed that an RDST-J score of ≤ 9 points provided 75.4% sensitivity and 95.2% specificity for identifying MCI, with an area under the curve of 0.899(95% CI: 0.835-0.964). The same cut-off value was identified when excluding patients with a high probability of dementia(RDST-J score of ≤ 4 points).CONCLUSIONS The RDST-J may be a simple and effective tool for identifying MCI in older patients with CVD.

Psychophysiological Effects of a Combination of Sideritis and Bacopa Extract (memoLoges®) in 32 Subjects Suffering from Mild Cognitive Impairment. A Double-Blind, Randomized, Placebo-Controlled, 2-Armed Study with Parallel Design

Mild cognitive impairment (MCI) can be regarded as a non-demented transitional stage during the development of Alzheimer’s disease. Early recognition of this stage might increase the chance of prevention by early treatment. Within a pilot study, two plant-derived preparations and mixtures thereof were tested successfully in subjects suffering from MCI. A combination of Sideritis scardica and Bacopa monnieri extract (memoLoges®) was chosen now for a repetitive dosing during 4 weeks. Thirty-two subjects aged 50 to 80 years and suffering from MCI (having a DemTect questionnaire score between 8 and 13) were recruited for intake of 2 capsules of the preparation per day. Quantitative EEG recording during relaxation and concomitant performance of three 5 minutes lasting psychometric tests (d2-concentration test, arithmetic calculation test and memory test) was achieved at the first day and one day after the last repetitive intake. Seventeen channels of EEG and one channel EOG (for artefact rejection) were recorded. After frequency analysis (FFT) current source density was calculated as reported earlier. One, two and three hours after intake of the herbal extract or placebo the whole procedure was repeated. Brain imaging was achieved by conversion of numerical values of spectral EEG power into spectral colors and additive color mixture according to RGB as used in TV settings. Intake of memoLoges® induced a trend of improvement of performance in psychometric testing (all three tests). During relaxation quantitative assessment of EEG data revealed attenuation of delta and theta spectral power in frontal brain as likewise reported in the presence of the Alzheimer drug rivastigmine, bringing the spectrum back to “normality”. During mental work memoLoges® induced statistically significant increases of beta power. Since MCI subjects produce less beta power in comparison to healthy subjects, this increase must likewise be seen as a positive effect pointing to a healthier spectrum.

IL-1β, TNF-α and Sambucus nigra Reactive Serum Proteins as Biomarkers of Mild Cognitive Impairment and Alzheimer Disease Progression

Amyloid-β (Aβ) can induce a chronic inflammatory immune response that is associated, amongst many others, to abnormal glycosylation, inducible nitric oxide synthase (iNOS) and nitric oxide (NO). The relation between development of Mild Cognitive Impairment (MCI) and Alzheimer’s disease progression and these serum markers has not been evaluated. Serum levels of iNOs, NO, TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12 are determined with commercially available kits. Sialylation of albumin-free serum patterns is determined by Western blot analysis with Sambucus nigra (specific for sialic acid attached to terminal galactose in α2,6 linkage) lectin. Apolipoprotein E (ApoE) haplotype is determined by Western blot using specific anti-ApoE 2, 3 or 4 antibodies. A mini-mental state examination (MMSE) test is also performed in the 10 MCI patients, 19 Alzheimer’s disease (AD) patients and 46 healthy age-matched controls evaluated. The results show an increase of iNOS in MCI and AD but significantly higher NO concentrations are only found in MCI patients. TNF-α and IL-1β concentrations are the only significantly increased cytokines in MCI patients;no differences between control and MCI or AD patients are found in regard to the other cytokines. An abnormal MMSE test result only correlates with a decrease in serum NO concentration in MCI patients. The terminal sialic acid linkage pattern of serum proteins also shows highly significant differences between MCI and AD patient. ApoE3/4 or 4/4 haplotypes are characteristic of MCI and AD patients. Our results imply that increased serum TNF-α, IL-1β, iNOS, NO and alterations of serum proteins glycosylation patterns in adult individuals with an abnormal MMSE test may serve as an early biomarker of MCI and AD development.

Effects of Ginkgo Biloba Special Extract EGb 761^(█) in Very Mild Cognitive Impairment(vMCI)

Objective: To assess effects of EGb 761? on cognition and quality of life in subjects with very mild cognitive impair-ment. Methods: We randomized 300 subjects aged 45 to 65 with cognitive complaints and low functioning (more than one standard deviation below appropriate norm) in at least one cognitive test to double-blind treatment with once daily 240 mg EGb 761? or placebo for 12 weeks. Results: The exploratory intention-to-treat analysis showed significant im-provement (p < 0.025, one-sided) beyond practice effects for EGb 761? in a measure of attention (Vienna Test System - Work Performance Series) and trends in favour of EGb 761? in measures of memory (Wechsler Memory Scale III - Faces I, Appointments Test – delayed recall), and perceived physical health (SF36 - factor score Physical Health). Cognitive effects were more pronounced and more consistent (p < 0.025 in 4 of 5 tests) in subjects with lower memory function at baseline. Specifically, practice effects in the more demanding tests were attenuated or absent in these sub-jects. Conclusion: Ginkgo biloba extract EGb 761? improved cognitive functioning and aspects of quality of life in sub-jects with very mild cognitive impairment.

White matter changes in 80 mild cognitive impairment patients using magnetic resonance imaging

BACKGROUND： Many studies have suggested that one possible etiology of mild cognitive impairment is small vessel cerebrovascular disease, which is associated with small subcortical infarcts and white matter abnormalities. These white matter changes have been detected as white matter hyperintensity （WMH） using magnetic resonance imaging. WMH may be associated with frontal lobe dysfunction. OBJECTIVE： To examine white matter changes in mild cognitive impairment patients of different subtypes, and to evaluate the correlation between white matter changes and neuropsychological characteristics, demographic information, vascular risk factors, and mild cognitive impairment subtypes. DESIGN, TIME AND SETTING： The neurophysiological, comparison study was performed at the Department of Neurology Memory Clinic, Ulsan University Hospital, South Korea, between March 2007 and March 2008. PARTICIPANTS： Out of a total of 83 subjects with clinically diagnosed mild cognitive impairment at the out-patient clinic, 3 subjects with severe WMH were excluded. A total of 80 subjects were included in this study. No patients suffered from cognitive impairment induced by neurological diseases, mental disorders, or somatic diseases. In accordance with magnetic resonance imaging results, the patients were assigned to two subtypes： 56 subjects without WMH and 24 subjects with WMH. METHODS： All patients were subjected to a standard neuropsychological battery using the Korean version of the Mini-Mental State Examination, Clinical Dementia Rating, and comprehensive Seoul Neuropsychological Screening Battery. The Clinical Dementia Rating reflected general cognitive function of patients. Results from the Seoul Neuropsychological Screening Battery reflected attention, language function, visuospatial function, verbal memory, nonverbal memory, long-term memory, and frontal/executive function. Magnetic resonance imaging was used to map changes in the brain. MAIN OUTCOME MEASURES： The association between various white matter changes and neuropsychological characteristics, demographic information, vascular risk factors, and mild cognitive impairment subtypes was measured, based primarily on neuropsychological profiles using statistical methods. RESULTS： WMH was significantly associated with neuropsychological characteristics in MCI patients （P 〈 0.05 or P 〈 0.01）, in particular with frontal/executive dysfunction. WMH was significantly correlated with age （P = 0.022） and vascular risk factors （P = 0.006）, independent of gender and MCI subtypes. CONCLUSION： WMH was significantly associated with frontal/executive dysfunction in mild cognitive impairment.