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1.
Sei J. Lee Christine S. Ritchie Kristine Yaffe Irena Stijacic Cenzer Deborah E. Barnes 《PloS one》2014,9(12)
Background
Mild cognitive impairment is often a precursor to dementia due to Alzheimer''s disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment.Objective
To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings.Design and Participants
382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer''s Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study.Main Predictors Measures
Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales.Main Outcome Measure
Progression to probable Alzheimer''s disease.Key Results
Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer''s disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell''s c-statistic was 0.71(95% CI: 0.68–0.75). Fourteen percent of subjects with low risk scores (0–2 points, n = 124) converted to probable Alzheimer''s disease over 3 years, compared to 51% of those with moderate risk scores (3–8 points, n = 223) and 91% of those with high risk scores (9–16 points, n = 35).Conclusions
An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer''s disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression. 相似文献2.
Background
Human brain aging has received special attention in part because of the elevated risks of neurodegenerative disorders such as Alzheimer''s disease in seniors. Recent technological advances enable us to investigate whether similar mechanisms underlie aging and neurodegeneration, by quantifying the similarities and differences in their genome-wide gene expression profiles.Principal Findings
We have developed a computational method for assessing an individual''s “physiological brain age” by comparing global mRNA expression datasets across a range of normal human brain samples. Application of this method to brains samples from select regions in two diseases – Alzheimer''s disease (AD, superior frontal gyrus), frontotemporal lobar degeneration (FTLD, in rostral aspect of frontal cortex ∼BA10) – showed that while control cohorts exhibited no significant difference between physiological and chronological ages, FTLD and AD exhibited prematurely aged expression profiles.Conclusions
This study establishes a quantitative scale for measuring premature aging in neurodegenerative disease cohorts, and it identifies specific physiological mechanisms common to aging and some forms of neurodegeneration. In addition, accelerated expression profiles associated with AD and FTLD suggest some common mechanisms underlying the risk of developing these diseases. 相似文献3.
Andreas Deistung Ferdinand Schweser Benedikt Wiestler Mario Abello Matthias Roethke Felix Sahm Wolfgang Wick Armin Michael Nagel Sabine Heiland Heinz-Peter Schlemmer Martin Bendszus Jürgen Rainer Reichenbach Alexander Radbruch 《PloS one》2013,8(3)
Objectives
The application of susceptibility weighted imaging (SWI) in brain tumor imaging is mainly used to assess tumor-related “susceptibility based signals” (SBS). The origin of SBS in glioblastoma is still unknown, potentially representing calcifications or blood depositions. Reliable differentiation between both entities may be important to evaluate treatment response and to identify glioblastoma with oligodendroglial components that are supposed to present calcifications. Since calcifications and blood deposits are difficult to differentiate using conventional MRI, we investigated whether a new post-processing approach, quantitative susceptibility mapping (QSM), is able to distinguish between both entities reliably.Materials and Methods
SWI, FLAIR, and T1-w images were acquired from 46 patients with glioblastoma (14 newly diagnosed, 24 treated with radiochemotherapy, 8 treated with radiochemotherapy and additional anti-angiogenic medication). Susceptibility maps were calculated from SWI data. All glioblastoma were evaluated for the appearance of hypointense or hyperintense correlates of SBS on the susceptibility maps.Results
43 of 46 glioblastoma presented only hyperintense intratumoral SBS on susceptibility maps, indicating blood deposits. Additional hypointense correlates of tumor-related SBS on susceptibility maps, indicating calcification, were identified in 2 patients being treated with radiochemotherapy and in one patient being treated with additional anti-angiogenic medication. Histopathologic reports revealed an oligodendroglial component in one patient that presented calcifications on susceptibility maps.Conclusions
QSM provides a quantitative, local MRI contrast, which reliably differentiates between blood deposits and calcifications. Thus, quantitative susceptibility mapping appears promising to identify rare variants of glioblastoma with oligodendroglial components non-invasively and may allow monitoring the role of calcification in the context of different therapy regimes. 相似文献4.
A. David Smith Stephen M. Smith Celeste A. de Jager Philippa Whitbread Carole Johnston Grzegorz Agacinski Abderrahim Oulhaj Kevin M. Bradley Robin Jacoby Helga Refsum 《PloS one》2010,5(9)
Background
An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.Objective
To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).Methods and Findings
Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.Results
A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.Conclusions and Significance
The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer''s disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer''s disease, trials are needed to see if the same treatment will delay the development of Alzheimer''s disease.Trial Registration
Controlled-Trials.com ISRCTN94410159 相似文献5.
Salvatore Nigro Antonio Cerasa Giancarlo Zito Paolo Perrotta Francesco Chiaravalloti Giulia Donzuso Franceso Fera Eleonora Bilotta Pietro Pantano Aldo Quattrone the Alzheimer's Disease Neuroimaging Initiative 《PloS one》2014,9(1)
Purpose
This paper describes a novel method to automatically segment the human brainstem into midbrain and pons, called LABS: Landmark-based Automated Brainstem Segmentation. LABS processes high-resolution structural magnetic resonance images (MRIs) according to a revised landmark-based approach integrated with a thresholding method, without manual interaction.Methods
This method was first tested on morphological T1-weighted MRIs of 30 healthy subjects. Its reliability was further confirmed by including neurological patients (with Alzheimer''s Disease) from the ADNI repository, in whom the presence of volumetric loss within the brainstem had been previously described. Segmentation accuracies were evaluated against expert-drawn manual delineation. To evaluate the quality of LABS segmentation we used volumetric, spatial overlap and distance-based metrics.Results
The comparison between the quantitative measurements provided by LABS against manual segmentations revealed excellent results in healthy controls when considering either the midbrain (DICE measures higher that 0.9; Volume ratio around 1 and Hausdorff distance around 3) or the pons (DICE measures around 0.93; Volume ratio ranging 1.024–1.05 and Hausdorff distance around 2). Similar performances were detected for AD patients considering segmentation of the pons (DICE measures higher that 0.93; Volume ratio ranging from 0.97–0.98 and Hausdorff distance ranging 1.07–1.33), while LABS performed lower for the midbrain (DICE measures ranging 0.86–0.88; Volume ratio around 0.95 and Hausdorff distance ranging 1.71–2.15).Conclusions
Our study represents the first attempt to validate a new fully automated method for in vivo segmentation of two anatomically complex brainstem subregions. We retain that our method might represent a useful tool for future applications in clinical practice. 相似文献6.
Devasuda Anblagan Nia W. Jones Carolyn Costigan Alexander J. J. Parker Kirsty Allcock Rosanne Aleong Lucy H. Coyne Ruta Deshpande Nick Raine-Fenning George Bugg Neil Roberts Zdenka Pausova Tomá? Paus Penny A. Gowland 《PloS one》2013,8(7)
Objective
To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta.Design
A case-control study, with operators performing the image analysis blinded.Setting
Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom.Participants
A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy.Methods
Each fetus was scanned with MRI at 22–27 weeks and 33–38 weeks gestational age (GA).Main outcome measures
Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes.Results
Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume.Conclusion
Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women. 相似文献7.
Jesús de Pedro-Cuesta Ignacio Mahillo-Fernandez Miguel Calero Alberto Rábano Mabel Cruz ?ke Siden Pablo Martínez-Martín Henning Laursen María Ruiz-Tovar K?re M?lbak 《PloS one》2014,9(10)
Introduction
Sporadic Creutzfeldt-Jakob disease (sCJD) might be transmitted by surgery. The purpose of this study was to investigate potential susceptibility to sCJD from surgery at juvenile age and in early adulthood.Methods
From Danish and Swedish national registries we identified 167 definite and probable sCJD cases with onset from 1987 through 2003, and 835 age-, sex- and residence-matched controls along with their surgical histories. Main, anatomically or etiologically classified surgical procedures followed by a ≥20-year lag were analyzed using logistic regression, and stratified by age at first-registered surgical discharge.Results
The risk of having a diagnosis of CJD depended strongly on age at first surgery with odds ratio (OR) of 12.80 (95% CI 2.56–64.0) in patients <30 years, 3.04 (95% 1.26–7.33) in 30–39 years, and 1.75 (95% CI 0.89–3.45) in ≥40 years, for anatomically classified surgical procedures. Similar figures were obtained for etiologically classified surgical procedures.Conclusions
Risk of surgical-acquired sCJD depends on age at exposure; this pattern is similar to age-specific profiles reported for CJD accidentally transmitted by human pituitary-derived growth hormone and susceptibility curves for variant CJD estimated after adjustment for dietary exposure to bovine spongiform encephalopathy. There might be an age-at-exposure-related susceptibility to acquire all CJD forms, including sCJD from routine surgery. 相似文献8.
Christian Pradier Charlotte Sakarovitch Franck Le Duff Richard Layese Asya Metelkina Sabine Anthony Karim Tifratene Philippe Robert 《PloS one》2014,9(8)
The aim of this study
was firstly to describe the MMSE (Mini-Mental State Examination) score upon initial diagnosis of Alzheimer''s disease and related disorders among the French population, according to age. Secondly, education, gender and place of residence were studied as factors potentially associated with delayed Alzheimer''s disease diagnosis.Design
we conducted a cross sectional analysis of the French National Alzheimer database (BNA). Data from 2008 to 2012 were extracted. Patients were selected at the moment of their first diagnosis of AD (n = 39,451).Results
The MMSE score at initial diagnosis dropped significantly with increasing age. The test score increased with the degree of educational background regardless of age. Gender and place of residence were significantly related to the MMSE score, women and persons living in medical institutions having lower MMSE scores under the age of 90 years and at all educational levels.Conclusions
Health care professionals should be aware of these risk factors in order to maximize chances of earliest possible diagnosis of Alzheimer''s disease and related disorders. 相似文献9.
Jakub Pazdrowski Pieńkowski Piotr Magdalena Kordylewska Anna Wegner Paweł Golusiński Wojciech Golusiński 《Reports of Practical Oncology and Radiotherapy》2010,15(3):60-63
Background
The exact assessment of a tonsil carcinoma''s size is often difficult because of the tumour''s submucosal extension and deep infiltration.Aim
The aim of the study is to assess the usefulness of intraoperative ultrasonography in tonsil cancer.Material
Twenty patients with carcinoma of the tonsil were included in the study (squamous cell carcinoma keratosis – 12, squamous cell carcinoma akeratosis – 6, diffuse large B cell lymphoma – 1, neoplasma malignum microcellulare – 1).Method
Transcutaneous, endoscopic, and intraoperative ultrasonography were performed using a linear 7.5 MHz probe.Results
The difference in the results was statistically significant between palpation examination and intraoperative ultrasonographic examination, between transcutaneous ultrasonographic examination and intraoperative ultrasonographic examination, and between endoscopic ultrasonographic examination and intraoperative ultrasonographic examination in tonsil tumours. Generally, tumour size assessed by intraoperative ultrasonography was more advanced than those assessed by other methods.Conclusions
Intraoperative ultrasonography is a safe, non-invasive method, which can be repeated at every stage of surgery. There were no contraindications or side effects. In all cases histological margins corresponded to sonographic margins. Intraoperative ultrasonography provides a quick and reliable orientation during resection of tonsil carcinoma. 相似文献10.
Background
Acetylcholinesterase inhibitors (AChEIs) are widely used to delay cognitive decline in Alzheimer''s disease. Observational studies in routine clinical practice have shown cognitive improvement in some groups of patients receiving these agents but longitudinal trajectories before and after AChEI initiation have not previously been considered.Objectives
To compare trajectories of cognitive function before and after AChEI initiation and investigate predictors of these differences.Method
A retrospective longitudinal study was constructed using data from 2460 patients who received AChEIs and who had routine data on cognitive function (Mini-Mental State Examination; MMSE) before and after AChEI initiation. Longitudinal MMSE change was modelled using three-piece linear mixed models with the following segments: 0–12 months prior to AChEI initiation, 0–6 months and 6–36 months after initiation.Results
MMSE decline was reversed (in that the slope was improved by an average 4.2 units per year, 95% CI 3.5–4.8) during the 6-month period following AChEI initiation compared with the slope in the one year period before AChEI initiation. The slope in the period from 6–36 months following AChEI initiation returned to the pre-initiation downward trajectory. The differences in slopes in the 1 year period prior to AChEI initiation and in the 6 months after initiation were smaller among those with higher MMSE scores at the time of AChEI initiation, among those who received a vascular dementia diagnosis at any point, and among those receiving antipsychotic agents.Conclusion
In this naturalistic observational study, changes in cognitive trajectories around AChEI initiation were similar to those reported in randomised controlled trials. The magnitude of the difference in slopes between the 1 year period prior to AChEI initiation and the 6 month period after AChEI initiation was related to level of cognitive function at treatment initiation, vascular comorbidity and antipsychotic use. 相似文献11.
Object
The aim of this study was to determine the suitability of magnetic resonance spectroscopy (MRS) for screening brain tumors, based on a systematic review and meta-analysis of published data on the diagnostic performance of MRS.Methods
The PubMed and PHMC databases were systematically searched for relevant studies up to December 2013. The sensitivities and specificities of MRS in individual studies were calculated and the pooled diagnostic accuracies, with 95% confidence intervals (CI), were assessed under a fixed-effects model.Results
Twenty-four studies were included, comprising a total of 1013 participants. Overall, no heterogeneity of diagnostic effects was observed between studies. The pooled sensitivity and specificity of MRS were 80.05% (95% CI = 75.97%–83.59%) and 78.46% (95% CI: 73.40%–82.78%), respectively. The area under the summary receiver operating characteristic curve was 0.78. Stratified meta analysis showed higher sensitivity and specificity in child than adult. CSI had higher sensitivity and SV had higher specificity. Higher sensitivity and specificity were obtained in short TE value.Conclusion
Although the qualities of the studies included in the meta-analysis were moderate, current evidence suggests that MRS may be a valuable adjunct to magnetic resonance imaging for diagnosing brain tumors, but requires selection of suitable technique and TE value. 相似文献12.
Background
In pediatric oncology, effective clinic–based management of acute and long–term distress in families calls for investigation of determinants of parents'' psychological response to the child''s cancer. We examined the relationship between parents'' prior exposure to traumatic life events (TLE) and the occurrence of posttraumatic stress symptoms (PTSS) following their child''s cancer diagnosis. Factors mediating the TLE–PTSS relationship were analyzed.Methodology
The study comprised 169 parents (97 mothers, 72 fathers) of 103 cancer diagnosed children (median age: 5,9 years; range 0.1–19.7 years). Thirty five parents were of immigrant origin (20.7%). Prior TLE were collated using a standardized questionnaire, PTSS was assessed using the Impact of Events–Revised (IES–R) questionnaire covering intrusion, avoidance and hyperarousal symptoms. The predictive significance of prior TLE on PTSS was tested in adjusted regression models.Results
Mothers demonstrated more severe PTSS across all symptom dimensions. TLE were associated with significantly increased hyperarousal symptoms. Parents'' gender, age and immigrant status did not significantly influence the TLE–PTSS relationship.Conclusions
Prior traumatic life–events aggravate posttraumatic hyperarousal symptoms. In clinic–based psychological care of parents of high–risk pediatric patients, attention needs to be paid to life history, and to heightened vulnerability to PTSS associated with female gender. 相似文献13.
Christer Nilsson Maria Landqvist Wald? Karin Nilsson Alexander Santillo Susanna Vestberg 《PloS one》2014,9(4)
Objectives
Frontotemporal dementia (FTD) is considered to be a mainly early-onset neurodegenerative disorder with a strong hereditary component. The aim of the study was to investigate age-related incidence and family history in FTD compared to other dementia disorders, especially Alzheimer''s disease (AD).Methods
The Swedish Dementia Registry (SveDem) registers all new cases of dementia diagnosed by the participating centres, including data on demographics, diagnosis, and investigations used. Data for the period 2008–2011 were extracted and compared with age-related population data on a regional and national level.Results
There were 20 305 patients registered in SveDem during 2008–2011, whereof 352 received a diagnosis of FTD. Mean age at diagnosis for FTD was 69.6 years and almost 70% of FTD cases were 65 years or older at the time of diagnosis. Both FTD and AD showed an increased incidence with age, which reached a maximum in the age group 80–84 years at 6.04 and 202 cases per 100 000 person-years, respectively. The proportion of cases with a positive family history was significantly lower in FTD than in AD.Conclusions
Contrary to general opinion within the field, data from SveDem show that the incidence of FTD increases with age, and that the majority of cases are diagnosed after the age of 65 years. In addition, data from SveDem might suggest that the importance of hereditary factors in general is similar in FTD and AD. The recognition of these findings has important consequences for the diagnosis, treatment and care of patients with FTD. 相似文献14.
《PloS one》2010,5(11)
Background
Late Onset Alzheimer''s disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.Methodology
We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.Principal Findings
We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.Significance
Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer''s disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches. 相似文献15.
O'Bryant SE Xiao G Barber R Huebinger R Wilhelmsen K Edwards M Graff-Radford N Doody R Diaz-Arrastia R;Texas Alzheimer's Research & Care Consortium;Alzheimer's Disease Neuroimaging Initiative 《PloS one》2011,6(12):e28092
Context
There is no rapid and cost effective tool that can be implemented as a front-line screening tool for Alzheimer''s disease (AD) at the population level.Objective
To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma.Design, Setting, Participants
Analysis of serum biomarker proteins were conducted on 197 Alzheimer''s disease (AD) participants and 199 control participants from the Texas Alzheimer''s Research Consortium (TARC) with further analysis conducted on plasma proteins from 112 AD and 52 control participants from the Alzheimer''s Disease Neuroimaging Initiative (ADNI). The full algorithm was derived from a biomarker risk score, clinical lab (glucose, triglycerides, total cholesterol, homocysteine), and demographic (age, gender, education, APOE*E4 status) data.Major Outcome Measures
Alzheimer''s disease.Results
11 proteins met our criteria and were utilized for the biomarker risk score. The random forest (RF) biomarker risk score from the TARC serum samples (training set) yielded adequate accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) = 0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI cerebral spinal fluid (CSF) analyses (t-tau/Aβ ratio AUC = 0.92). However, the full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91). The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03 (SE = 1.17; 95% CI = 4.49–14.47), the likelihood ratio of not having AD based on the algorithm (LR−) = 3.55 (SE = 1.15; 2.22–5.71), and the odds ratio of AD were calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86–69.47).Conclusions
It is possible to create a blood-based screening algorithm that works across both serum and plasma that provides a comparable screening accuracy to that obtained from CSF analyses. 相似文献16.
Steffen Wolfsgruber Michael Wagner Klaus Schmidtke Lutz Fr?lich Alexander Kurz Stefanie Schulz Harald Hampel Isabella Heuser Oliver Peters Friedel M. Reischies Holger Jahn Christian Luckhaus Michael Hüll Hermann-Josef Gertz Johannes Schr?der Johannes Pantel Otto Rienhoff Eckart Rüther Fritz Henn Jens Wiltfang Wolfgang Maier Johannes Kornhuber Frank Jessen 《PloS one》2014,9(7)
Background
Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer''s dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).Methods
We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.Results
Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.Conclusions
Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients'' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI. 相似文献17.
María-Salud García-Ayllón Iolanda Riba-Llena Carol Serra-Basante Jordi Alom Rathnam Boopathy Javier Sáez-Valero 《PloS one》2010,5(1)
Background
Many studies have been conducted in an extensive effort to identify alterations in blood cholinesterase levels as a consequence of disease, including the analysis of acetylcholinesterase (AChE) in plasma. Conventional assays using selective cholinesterase inhibitors have not been particularly successful as excess amounts of butyrylcholinesterase (BuChE) pose a major problem.Principal Findings
Here we have estimated the levels of AChE activity in human plasma by first immunoprecipitating BuChE and measuring AChE activity in the immunodepleted plasma. Human plasma AChE activity levels were ∼20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G1+G2 forms and not G4 tetramers. The levels and pattern of the molecular forms are similar to that observed in individuals with silent BuChE. We have also compared plasma AChE with the enzyme pattern obtained from human liver, red blood cells, cerebrospinal fluid (CSF) and brain, by sedimentation analysis, Western blotting and lectin-binding analysis. Finally, a selective increase of AChE activity was detected in plasma from Alzheimer''s disease (AD) patients compared to age and gender-matched controls. This increase correlates with an increase in the G1+G2 forms, the subset of AChE species which are increased in Alzheimer''s brain. Western blot analysis demonstrated that a 78 kDa immunoreactive AChE protein band was also increased in Alzheimer''s plasma, attributed in part to AChE-T subunits common in brain and CSF.Conclusion
Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation. 相似文献18.
Study objectives
To search for early abnormalities in electroencephalogram (EEG) during sleep which may precede motor symptoms in a transgenic mouse model of hereditary neurodegenerative Huntington’s disease (HD).Design
In the R6/1 transgenic mouse model of HD, rhythmic brain activity in EEG recordings was monitored longitudinally and across vigilance states through the onset and progression of disease.Measurements and results
Mice with chronic electrode implants were recorded monthly over wake-sleep cycles (4 hours), beginning at 9–11 weeks (presymptomatic period) through 6–7 months (symptomatic period). Recording data revealed a unique β rhythm (20–35 Hz), present only in R6/1 transgenic mice, which evolves in close parallel with the disease. In addition, there was an unusual relationship between this β oscillation and vigilance states: while nearly absent during the active waking state, the β oscillation appeared with drowsiness and during slow wave sleep (SWS) and, interestingly, strengthened rather than dissipating when the brain returned to an activated state during rapid eye movement (REM) sleep.Conclusions
In addition to providing a new in vivo biomarker and insight into Huntington''s disease pathophysiology, this serendipitous observation opens a window onto the rarely explored neurophysiology of the cortico-basal ganglia circuit during SWS and REM sleep. 相似文献19.
Purpose
Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormone''s effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury.Methods
Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1–7, subjected to behavioral testing from PID 9–27, and analyzed for lesion size at PID 28.Results
The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats.Conclusion
Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits. 相似文献20.
Hogne Soennesyn Dennis W. Nilsen Ketil Oppedal Ole Jacob Greve Mona K. Beyer Dag Aarsland 《PloS one》2012,7(12)