Search

The pathophysiology of amnestic Mild Cognitive Impairment (aMCI) is largely unknown, although some papers found signs of immune activation. To assess the cytokine network in aMCI after excluding patients with major depression (MDD) and to examine the immune profiles of quantitative aMCI (qMCI) and distress symptoms of old age (DSOA) scores. A case-control study was conducted on 61 Thai aMCI participants and 60 healthy old adults (both without MDD). The Bio-Plex Pro human cytokine 27-plex test kit was used to assay cytokines/chemokines/growth factors in fasting plasma samples. aMCI is characterized by a significant immunosuppression, and reductions in T helper 1 (Th)1 and T cell growth profiles, the immune-inflammatory responses system, interleukin (IL)1β, IL6, IL7, IL12p70, IL13, GM-CSF, and MCP-1. These 7 cytokines/chemokines exhibit neuroprotective effects at physiologic concentrations. In multivariate analyses, three neurotoxic chemokines, CCL11, CCL5, and CXCL8, emerged as significant predictors of aMCI. Logistic regression showed that aMCI was best predicted by combining IL7, IL1β, MCP-1, years of education (all inversely associated) and CCL5 (positively associated). We found that 38.2% of the variance in the qMCI score was explained by IL7, IL1β, MCP-1, IL13, years of education (inversely associated) and CCL5 (positively associated). The DSOA was not associated with any immune data. An imbalance between lowered levels of neuroprotective cytokines and chemokines, and relative increases in neurotoxic chemokines are key factors in aMCI. Future MCI research should always control for the confounding effects of affective symptoms., (© 2024. The Author(s).)

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP ( n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aβ42/Aβ40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aβ42/Aβ40 (rho = -0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized β = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.

Introduction: Novel plasma biomarkers are promising for identifying Alzheimer's disease (AD) pathological processes in vivo, but most currently employed assays have limitations precluding widespread use., Methods: CSF and plasma samples were collected from seventy amnestic mild cognitive impairment (aMCI) subjects, stratified as A+ and A-. CSF Aβ40, Aβ42, p-tau181 and t-tau and plasma Aβ40, Aβ42 and p-tau181 quantification were conducted using the Lumipulse G assays (Fujirebio), to evaluate the diagnostic performance of plasma biomarkers and assess their associations with CSF biomarkers., Results: All plasma biomarkers except Aβ40 showed a very good accuracy in distinguishing A+ aMCI from A- aMCI, Aβ42/p-tau181 ratio being the most accurate (AUC 0.895, sensitivity 95.1%, specificity 82.8%). Plasma biomarkers levels were significantly associated with CSF biomarkers concentration., Discussion: High-throughput and fully-automated plasma assays could be helpful in discriminating with high accuracy between aMCI in the AD continuum and aMCI unlikely due to AD in clinical settings., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest.

Background: Long noncoding RNAs (lncRNAs) regulate the pathogenesis of Alzheimer's disease (AD)., Objective: To identify lncRNAs in the peripheral blood as potential diagnostic biomarkers for amnestic mild cognitive impairment., Methods: In the discovery group, a microarray was used to screen for significant differences in lncRNA expression between patients with mild cognitive impairment (MCI) caused by AD and normal controls (NCs) (n = 10; MCI, 5; NC, 5). Furthermore, two analytic groups were assessed (analytic group 1: n = 10; amnestic MCI (aMCI), 5; NC, 5; analytic group 2: n = 30; AD, 10; aMCI, 10; NC, 10) and finalized in the validation group (n = 150; AD, 50; aMCI, 50; NC, 50). In the analytic and validation groups, real-time quantitative reverse-transcription polymerase chain reaction was used to identify differentially expressed lncRNAs between the aMCI and NC groups., Results: We identified 67 upregulated and 220 downregulated lncRNAs among the expression profiles. The panel with lncRNAs T324988, NR_024049, ENST00000567919, and ENST00000549762 displayed the highest discrimination ability between patients with aMCI and NCs. The area under the receiver operating characteristic curve of this combined model was 0.941, with a sensitivity of 92.00% and specificity of 84.00%., Conclusions: This study reports on a panel of four lncRNAs as promising biomarkers to diagnose aMCIs.

Beta-secretase 1 (BACE1) is considered as the key enzyme in amyloid-β formation. Previous works suggest that high BACE1 activity may be present in brain, cerebrospinal fluid and serum of patients with late-onset Alzheimer's disease (LOAD) as well as mild cognitive impairment (MCI). Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI to dementia. BACE1 activity was measured in the serum of 259 MCI patients (162 amnestic-aMCI, 97 non-amnestic-naMCI) and 204 healthy Controls. After a median follow-up of 32 months (range: 10-153), 116 MCI progressed to dementia (87 aMCI and 29 naMCI). Serum BACE1 activity was higher in MCI compared with Controls (p < 0.001), and in aMCI with brain atrophy compared with naMCI without brain atrophy (p = 0.04). No difference in BACE1 activity emerged between converter and non-converter MCI, and this was true for both aMCI and naMCI. However, among aMCI with better cognitive performance (n. 163, MMSE score ≥24/30) those converting to dementia had higher BACE1 activity compared to stable ones (p = 0.05). This was not associated with an increased risk to develop dementia (hazard ratio: 1.65; 95% confidence interval: 0.67-4.01). In conclusion, serum BACE1 activity significantly increased in MCI patients (both amnestic and non-amnestic) compared with Controls. Moreover, higher serum BACE1 activity was observed only among aMCI with a better cognitive performance who progressed to dementia, suggesting that a dysregulation of this enzyme might be an early event primarily associated with neurodegeneration., (© 2021 International Society for Neurochemistry.)

Alpha 1-antichymotrypsin (ACT), an acute-phase protein, has been reported to be increased in the brain and blood of Alzheimer's disease (AD) patients. However, few previous studies have focused on amnestic mild cognitive impairment (aMCI) patients. The aim of our study was to investigate the changing trend in ACT concentrations during the progression of aMCI. Hence, we measured the cerebrospinal fluid (CSF) and serum levels of ACT in aMCI subjects and normal controls (NC) at 2-year follow-up assessments using ELISA and Western blot. Forty-four NCs, 28 stable aMCI (sMCI) patients, and 20 progressive aMCI (pMCI) patients finished the follow-up assessments, and their data were used for analysis. We found that CSF and serum ACT levels of both sMCI and pMCI patients increased over time, while those of NCs remained stable; CSF and serum ACT levels were significantly higher in both sMCI and pMCI patients than in NCs, except for baseline serum ACT. In pMCI patients prior to developing AD, CSF and serum ACT levels were already significantly higher than those in sMCI patients. The ROC curve results demonstrated that combining CSF and serum ACT levels can distinguish aMCI patients from NCs with high specificity and sensitivity. Our data suggest that ACT may be a biomarker for diagnosing aMCI.

Brain complexity, which reflects the ability of the brain to adapt to a changing environment, has been found to be significantly changed with age. However, there is less evidence on the alterations of brain complexity in neurodegenerative disorders such as Alzheimer's disease (AD). Here we investigated the altered complexity of resting-state blood oxygen level-dependent signals in AD-related neurodegeneration using multiscale entropy (MSE) analysis. All participants were recruited from the Alzheimer's Disease Neuroimaging Initiative, including healthy controls (HC, n=62), amnestic mild cognitive impairment (aMCI, n =81) patients, and Alzheimer's disease (AD, n=25) patients. Our results showed time scale-dependent MSE differences across the three groups. In scale=1, significantly changed MSE patterns (HC>aMCI>AD) were found in four brain regions, including the hippocampus, middle frontal gyrus, intraparietal lobe, and superior frontal gyrus. In scale=4, reversed MSE patterns (HC

Background: Recent work has supported use of blood-based biomarkers in detection of amnestic mild cognitive impairment (MCI). Inclusion of neuropsychological measures has shown promise in enhancing utility of biomarkers to detect disease., Objective: The present study sought to develop cognitive-biomarker profiles for detection of MCI., Methods: Data were analyzed on 463 participants (normal control n = 378; MCI n = 85) from HABLE. Random forest analyses determined proteomic profile of MCI. Separate linear regression analyses determined variance accounted for by select biomarkers per neuropsychological measure. When neuropsychological measure with the least shared variance was identified, it was then combined with select biomarkers to create a biomarker-cognitive profile., Results: The biomarker-cognitive profile was 90% accurate in detecting MCI. Among amnestic MCI cases, the detection accuracy of the biomarker-cognitive profile was 92% and increased to 94% with demographic variables., Conclusion: The biomarker-cognitive profile for MCI was highly accurate in its detection with use of only five biomarkers.

Aim: White matter hyperintensities (WMH) on MRI have been reported to be a risk factor for the conversion from mild cognitive impairment (MCI) to Alzheimer's disease, although the reason remains unclear. In the present study, we hence investigated the associations between WMH volumes and cognitive function, blood levels of various molecules, and the presence of lifestyle-associated diseases in patients with amnestic MCI., Methods: The initial data of 38 patients with amnestic MCI and 10 normal control individuals were analyzed. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on T2 fluid-attenuated inversion recovery using the imaging software, 3D Slicer; and the association between PVH/DWMH volumes and cognitive function, blood levels of molecules (such as cystatin C [CysC], 25-hydroxyvitamin D and homocysteine) and the presence of lifestyle-associated diseases (such as hypertension, hyperlipidemia and diabetes mellitus) were analyzed., Results: In the MCI group, the PVH volume : intracranial volume ratio significantly correlated with Trail Making Test-A/B scores and CysC level by Pearson's analysis, and the PVH volume : intracranial volume ratio significantly correlated with only CysC levels, whereas the DWMH volume : intracranial volume ratio did not correlate with any items at all by linear multiple regression analysis., Conclusions: PVH volume was closely associated with frontal lobe dysfunction, particularly with attention and executive dysfunction. Serum CysC level was associated with PVH volume, which suggests that CysC might be a useful marker for determining treatment strategies for white matter abnormalities in amnestic MCI. Geriatr Gerontol Int 2019; 19: 1036-1040., (© 2019 The Authors Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Levels of amyloid-β (Aβ) and tau peptides in brain have been associated with Alzheimer disease (AD). The current study investigated the abilities of plasma Aβ42 and total-tau (t-tau) levels in predicting cognitive decline in subjects with amnestic mild cognitive impairment (MCI). Plasma Aβ42 and t-tau levels were quantified in 22 participants with amnestic MCI through immunomagnetic reduction (IMR) assay at baseline. The cognitive performance of participants was measured through neuropsychological tests at baseline and annual follow-up (average follow-up period of 1.5 years). The predictive value of plasma Aβ42 and t-tau for cognitive status was evaluated. We found that higher levels of Aβ42 and t-tau are associated with lower episodic verbal memory performance at baseline and cognitive decline over the course of follow-up. While Aβ42 or t-tau alone had moderate-to-high discriminatory value in the identification of future cognitive decline, the product of Aβ42 and t-tau offered greater differential value. These preliminary results might suggest that high levels of plasma Aβ42 and t-tau in amnestic MCI are associated with later cognitive decline. A further replication with a larger sample over a longer time period to validate and determine their long-term predictive value is warranted.

Background: Amnestic mild cognitive impairment (aMCI) is considered to be a prodromal stage of Alzheimer's disease. The clinical role of ischaemia-modified albumin (IMA) and the association between IMA and oxidative stress in aMCI have not been investigated. The aim of the study was to explore this relationship and to generate new ideas for controlling Alzheimer's disease., Methods: This community-based case-control study included 113 patients with aMCI and 832 cognitively normal controls. Serum levels of albumin and IMA, diacron-reactive oxygen metabolite, and biological anti-oxidant potential, were measured. The IMA/albumin ratio and the biological anti-oxidant potential/diacron-reactive oxygen metabolite ratio were calculated., Results: In univariate analysis, the serum IMA level and the IMA/albumin ratio were higher in the aMCI patients than in the controls (P < 0.001, P < 0.001, respectively). In multivariate analysis, a serum IMA level ≥476.4 ng/mL and an IMA/albumin ratio ≥9.4 were separately associated with the development of aMCI (odds ratio = 3.56, 95% confidence interval: 2.33-5.46; odds ratio = 3.43, 95% confidence interval: 2.25-5.27, respectively). There was a linear correlation between serum IMA level and several oxidative stress markers (biological anti-oxidant potential/diacron-reactive oxygen metabolite ratio: r = -0.585, P < 0.001; diacron-reactive oxygen metabolite: r = 0.549, P < 0.001; biological anti-oxidant potential: r = -0.293, P < 0.001)., Conclusion: Serum IMA might be a potential biomarker for oxidative stress in aMCI., (© 2018 Japanese Psychogeriatric Society.)

It is an open issue whether blood biomarkers serve to diagnose Alzheimer's disease (AD) or monitor its progression over time from prodromal stages. Here, we addressed this question starting from data of the European FP7 IMI-PharmaCog/E-ADNI longitudinal study in amnesic mild cognitive impairment (aMCI) patients including biological, clinical, neuropsychological (e.g., ADAS-Cog13), neuroimaging, and electroencephalographic measures. PharmaCog/E-ADNI patients were classified as "positive" (i.e., "prodromal AD" n = 76) or "negative" (n = 52) based on a diagnostic cut-off of Aβ42/P-tau in cerebrospinal fluid as well as APOE ε 4 genotype. Blood was sampled at baseline and at two follow-ups (12 and 18 months), when plasma amyloid peptide 42 and 40 (Aβ42, Aβ40) and apolipoprotein J (clusterin, CLU) were assessed. Linear Mixed Models found no significant differences in plasma molecules between the "positive" (i.e., prodromal AD) and "negative" groups at baseline. In contrast, plasma Aβ42 showed a greater reduction over time in the prodromal AD than the "negative" aMCI group (p = 0.048), while CLU and Aβ40 increased, but similarly in the two groups. Furthermore, plasma Aβ42 correlated with the ADAS-Cog13 score both in aMCI patients as a whole and the prodromal AD group alone. Finally, CLU correlated with the ADAS-Cog13 only in the whole aMCI group, and no association with ADAS-Cog13 was found for Aβ40. In conclusion, plasma Aβ42 showed disease progression-related features in aMCI patients with prodromal AD.

Alcohol-induced amnesia ("blackout") is a reliable predictor of alcohol-related harm. Given its association with other negative consequences, experience of alcohol-induced amnesia may serve as a teachable moment, after which individuals are more likely to respond to intervention. To test this hypothesis, alcohol-induced amnesia was evaluated as a moderator of brief intervention effect on (a) alcohol-related consequences and (b) the proposed intervention mediators, protective behavioral strategies and peak blood alcohol concentration (BAC). Baseline alcohol risk measured using the Alcohol Use Disorders Identification Test (AUDIT) was also evaluated as a moderator to rule out the possibility that amnesia is simply an indicator of more general alcohol risk. College students (N = 198) reporting alcohol use in a typical week completed assessments at baseline and 1-month follow-up as part of a larger intervention trial. Participants were randomized to assessment only (AO; n = 58) or personalized feedback intervention (PFI; n = 140). Hierarchical regression was used to examine direct and indirect intervention effects. A significant group-by-amnesia interaction revealed that only PFI participants who had experienced alcohol-induced amnesia in the past month reported decreases in alcohol consequences at 1-month follow-up. The PFI reduced alcohol-related consequences indirectly through changes in peak BAC, but only among those who had experienced amnesia at baseline. In contrast, baseline alcohol risk (AUDIT) did not moderate intervention effects, and use of protective behavioral strategies did not statistically mediate intervention effects. Findings suggest that loss of memory for drinking events is a unique determinant of young adult response to brief alcohol intervention. Normative feedback interventions may be particularly effective for individuals who have experienced alcohol-induced amnesia in the past 30 days., (Copyright © 2018. Published by Elsevier Ltd.)

Background/rationale: Accumulating evidence suggests that the use of angiotensin-converting enzyme inhibitor (ACE-I) medication protects against cognitive decline in the elderly patients. We investigated whether ACE-I use was associated with higher plasma levels of amyloid-β (Aβ), possibly indicating improved Aβ clearance from brain to blood., Methods: We measured and compared plasma concentrations of Aβ42, Aβ40, and creatinine in cognitively impaired individuals with amnestic mild cognitive impairment, probable Alzheimer's disease (AD) dementia, and mixed probable AD/vascular dementia., Results: Plasma Aβ42 levels and Aβ42/Aβ40 ratios of participants taking ACE-Is (n = 11) significantly exceeded ( t = 3.1, df = 19, P = .006; U = 24, P = .029, respectively) those not taking ACE-Is (n = 10)., Conclusions: This study is the first to show an association between ACE-I use and increased plasma Aβ42 level and Aβ42/Aβ40 ratio in cognitively impaired individuals. Future investigations should assess whether a possible ACE-I-induced increase in plasma Aβ42 indicates improved Aβ42 clearance from brain that contributes to protection from cognitive decline.

Prediction of post-concussive syndrome after apparent mild traumatic brain injury (TBI) and subsequent cognitive recovery remains challenging, with substantial limitations of current methods of cognitive testing. This pilot study aimed to determine if levels of micro ribonucleic acids (RNAs) circulating in plasma are altered following TBI, and if changes to levels of such biomarkers over time could assist in determination of prognosis after TBI. Patients were enrolled after TBI on presentation to the Emergency Department and allocated to three groups: A - TBI (physical trauma to the head), witnessed loss of consciousness, amnesia, GCS=15, a normal CT Brain and a recorded first pass after post-traumatic amnesia (PTA) scale; B TBI, witnessed LOC, amnesia, GCS=15, a normal CT brain and a PTA scale test fail and: C - TBI and initial GCS <13 on arrival to the ED. Venous blood was collected at three time points (arrival, day 5 and day 30). Isolation of cell-free total RNA was then assayed using a custom miRNA PCR array. Two micro-RNAs, mir142-3p and mir423-3p demonstrated potential clinical utility differentiating patients after mild head injury into those at greater risk of developing amnesia and therefore, post-concussive syndromes. In addition, these miRNA demonstrated a decrease in expression over time, possibly indicative of brain healing after the injury. Further evaluation of these identified miRNA markers with larger patient cohorts, correlation with clinical symptoms and analysis over longer time periods are essential next steps in developing objective markers of severity of TBI., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA) are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T) biosynthesis, which is known to diminish traumatic brain injury (TBI)-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17)) or Sham injury (craniectomy alone; n = 12) and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16) or saline (n = 13) every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4) by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068), T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p < 0.05), 11-deoxycorticosterone (11-DOC) by 37.5% (from 289.3 ± 42.0 ng/mL to 180.7 ± 3.3 ng/mL), and corticosterone by 50.8% (from 195.1 ± 22.4 ng/mL to 95.9 ± 2.2 ng/mL), by post-surgery day 1. CCI injury induced similar declines in P4, T, 11-DOC and corticosterone (58.9%, 74.6%, 39.4% and 24.6%, respectively) by post-surgery day 1. These results suggest that both Sham surgery and CCI injury induce hypogonadism and hypoadrenalism in adult male rats. CLA treatment did not reverse hypogonadism in Sham (P4: 2.5 ± 1.0 ng/mL; T: 0.9 ± 0.2 ng/mL) or CCI-injured (P4: 2.2 ± 0.9 ng/mL; T: 1.0 ± 0.2 ng/mL, p > 0.05) animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL) and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL) animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s) compared to saline treated Sham animals (8.8 ± 1.7 s). In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s) compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05). These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1) does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse craniectomy- and craniectomy + CCI-induced hypoadrenalism, 2) is detrimental to medium- and long-term spatial learning and memory in craniectomized uninjured rats, 3) limits cognitive recovery following a moderate-severe CCI injury, and 4) does not alter body weight., Competing Interests: The authors have declared that no competing interests exist.

Aim: To perform therapeutic monitoring and prediction of the neurotrophic therapy efficacy in patients with amnestic type of mild cognitive impairment (aMCI) in a model of course cerebrolysin therapy., Material and Methods: The study involved a group of 19 elderly patients who met the diagnostic criteria of aMCI. All patients received a course of neurotrophic therapy consisting of 20 intravenous infusions of cerebrolysin (30 ml of cerebrolysin in 100 ml of isotonic sodium chloride solution). To assess the therapy efficacy, psychometric scales (CGI, MMSE, MoCA-test, МDRS, FAB, Clock Drawing Test, BNT, Word Recall test, delayed reproduction of 10 words, naming digits in a direct and reverse order) were used at 0, 4, 10 and 26 weeks of the study. Antibodies to p75 neurotrophin receptor (NTR) were measured by ELISA in blood serum of 19 patients before cerebrolysin therapy and after 10 and 26 weeks of treatment., Results and Conclusion: The study showed that аMCI patients had an increased level of antibodies against P75NTR that was significantly decreased after 5.5 month of cerebrolysin treatment. Therefore, it can be a potential biomarker of long-term therapeutic effect of cerebrolysin treatment in aMCI patients. The modified fragment 155-164 of P75 NTR determined in the serum of patients can be an effective indicator for monitoring and predicting the efficacy of long-term neurotrophic therapy.

Objectives: Alzheimer's disease (AD), the most common cause of dementia, is a progressive, incurable neurodegenerative disorder. Platelet is a suitable source of human peripheral tissue to study pathological mechanisms occurring in the brain. The present study aims to investigate (1) whether abnormal apoptotic events besides involved in AD within the central neurologic system, could also occur at peripheral platelet level; (2) whether apoptosis at peripheral platelet level starts at the early stage of AD., Patients and Methods: Amnestic mild cognitive impairment (MCI), AD, and age-matched healthy individuals were recruited, and each group had 50 person. In the present study, we investigate whether alterations of caspase family and Bcl2 family could be found in the platelets in Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) patients. The platelet levels of caspase protein and Bcl2 family were analyzed by western blot., Results: The results show that the platelet levels of caspase-3, caspase-9, Bad, and Bax significantly increased in AD and amnestic MCI. The increased apoptosis proteins levels in amnestic MCI were found between AD and normal controls. The anti-apoptosis protein Bcl2 increased in amnestic MCI, while decreased in AD., Conclusion: We suggest that increased apoptosis exist in the platelet and might mirror apoptosis within the brain. Abnormal apoptosis may appear in the early of AD, and the ratio between pro- and anti-apoptotic protein levels partially determines the susceptibility of platelet to a death signal. In conclusion, platelet may be a good model to study apoptotic pathways of AD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: The present study investigated the characteristics of amnestic mild cognitive impairment (aMCI) in subjects with low brain amyloid-beta (Aβ) burden. Furthermore, the relationships between amyloid-independent cognitive decline and serum lipid profiles, particularly apolipoprotein A1 (APOA1), were evaluated., Design: Cross-sectional and longitudinal follow-up study., Setting: University hospital dementia clinic., Participants: 28 aMCI and 35 cognitive normal (CN) elderly., Measurements: The study measures included baseline assessments of the subjects' clinical characteristics, lipid profiles, and magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B (PiB) positron emission tomography scans. Based on PiB retention at baseline, the aMCI subjects were divided into low Aβ (aMCI-) and high Aβ (aMCI+) subgroups. All aMCI subjects were followed up over a 1-year period., Results: The aMCI- group had a longer duration of illness than did the aMCI+ group. None of the aMCI- subjects were diagnosed with Alzheimer disease (AD) dementia during the 1-year follow-up period, whereas 26.7% of aMCI+ subjects developed AD dementia. The aMCI- group also exhibited lower serum APOA1 levels compared with both the aMCI+ and CN groups. Additionally, lower serum APOA1 levels were associated with cognitive decline and brain atrophy independent of Aβ deposition and vascular burden., Conclusions: Patients with aMCI- likely exhibit different clinical and pathophysiological characteristics than patients with aMCI+. Additionally, APOA1 may be an important contributor underlying amyloid-independent neurodegeneration., (Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) is one of the leading causes of neurological disability. In this retrospective study, serum total cholinesterase (ChE) activities were analyzed in 188 patients for diagnostic as well as predictive values for mortality., Methods and Findings: Within 72 hours after injury, serum ChE activities including both acetylcholinesterase and butyrylcholinesterase were measured. Disease severity was evaluated with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow Coma Score, length of coma, post-traumatic amnesia and injury feature. Neurocognitive and functional scores were assessed using clinical records. Of 188 patients, 146 (77.7%) survived and 42 (22.3%) died within 90 days. Lower ChE activities were noted in the non-survivors vs. survivors (5.94±2.19 vs. 7.04±2.16 kU/L, p=0.023), in septic vs. non-infected patients (5.93±1.89 vs. 7.31±2.45 kU/L, p=0.0005) and in patients with extremely severe injury vs. mild injury (6.3±1.98 vs. 7.57±2.48 kU/L, p=0.049). The trajectories of serum ChE levels were also different between non-survivors and survivors, septic and non-infected patients, mild and severely injured patients, respectively. Admission ChE activities were closely correlated with blood cell counts, neurocognitive and functional scores both on admission and at discharge. Receiver operating characteristic analysis showed that the area under the curve for ChE was inferior to that for either APACHE II or white blood cell (WBC) count. However, at the optimal cutoff value of 5 kU/L, the sensitivity of ChE for correct prediction of 90-day mortality was 65.5% and the specificity was 86.4%. Kaplan-Meier analysis showed that lower ChE activity (<5 kU/L) was more closely correlated with poor survival than higher ChE activity (>5 kU/L) (p=0.04). After adjusting for other variables, ChE was identified as a borderline independent predictor for mortality as analyzed by Binary logistic regression (P=0.078)., Conclusions: Lowered ChE activity measured on admission appears to be associated with disease severity and outcome for TBI patients.

Objective: To investigate the relationship between microRNA107 (miRNA107) and BACE1 messenger RNA (mRNA) gene expressions in plasma and their diagnostic capability to distinguish subjects with amnestic mild cognitive impairment from healthy controls., Method: We recruited 97 patients with Alzheimer's disease according to diagnostic criteria of DSM-IV and National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association, 116 subjects with amnestic mild cognitive impairment, and 81 healthy controls from January 2012 to December 2012. The real-time PCR was used to quantify miRNA107 and BACE1 mRNA. The power of classification accuracies between patients with amnestic mild cognitive impairment and healthy controls was performed using linear discriminate analysis single or combining both the expression miRNA107 and BACE1 mRNA., Results: For patients with Alzheimer's disease, the miRNA107 expressions in plasma and cerebral spinal fluid were correlated (Pearson correlation = 0.665, P = .034). There were statistically significant correlations between plasma miRNA107 and BACE1 mRNA gene expression in Alzheimer's disease, amnestic mild cognitive impairment, and healthy control groups (r value = -0.316 [P = .002], -0.615 [P < .001], and -0.367 [P = .001], respectively). The overall classification accuracy of miRNA107 to discriminate between patients with amnestic mild cognitive impairment and healthy controls was 91.9%, with sensitivity of 98.3% and specificity of 82.7%., Conclusions: The miRNA107 expression in plasma has a high capability to discriminate between patients with amnestic mild cognitive impairment and healthy controls., Trial Registration: ClinicalTrials.gov identifier: NCT01819545., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Alzheimer's disease (AD) is the most common type of dementia in the elderly. The accumulation of amyloid-β peptides and tau proteins is the major pathogenic event of AD. There is accumulating evidence that both tau and amyloid-β linked to the small ubiquitin-like modifier (SUMO), which is increased in the brain of AD model mouse. The present study focused on the determination of SUMO1 protein level in AD blood plasma by the ELISA methods. We compared plasma from 80 dementia patients (average age 75.3 y), 89 persons with amnestic mild cognitive impairment (MCI) (average age 73.71 y),and 133 cognitively normal controls (average age 71.97 y). The plasma level of SUMO1 was significantly increased in dementia patients, as compared to control groups. The levels of SUMO1 correlated to decreased Mini-Mental State Examination (r =-0.123, p = 0.029). These results suggest that elevated plasma SUMO1 levels may be associated with AD.

Objective: To prospectively monitor plasma inflammatory marker concentrations in peripheral blood, over 12 months, in subjects with amnestic mild cognitive impairment (MCI), and to determine the relationship between peripheral inflammatory markers and cognitive decline., Methods: Seventy patients with amnestic MCI were recruited from two sites providing specialist memory assessment services in Manchester. The baseline assessment included physical examination, neuro-psychological testing and venous blood samples for C-reactive protein (CRP) and interleukin 6 (IL-6) concentrations. Sixty two participants were followed up after 12 months and the assessments were repeated., Results: Data analysis revealed a significant rise in CRP, but not IL-6 concentrations over 12 months, which was not confounded by demographic variables. The neuro-psychological test scores had no association with CRP or IL-6 concentrations at baseline or 12 months follow-up., Conclusion: This study adopted the unique approach of prospectively investigating peripheral inflammatory markers in a cohort with amnestic MCI. A significant rise in CRP concentrations over 12 months, but lack of significant association with cognition, provide no evidence for a relationship between systemic inflammation and cognitive decline in amnestic MCI., (© 2013 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.)

Growing evidence suggests that angiogenesis might represent a new pathogenic mechanism involved in the progression of Alzheimer's disease (AD). Vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) are two cytokines having a pivotal role in angiogenesis. In the present study, serum VEGF and TGF-β1 levels were measured with ELISA in 31 AD patients, 28 amnestic mild cognitive impairment (aMCI) patients and 29 controls. VEGF concentration in serum of AD patients was significantly lower than that in aMCI patients and controls (p<0.05). Serum VEGF levels in aMCI patients were also significantly decreased compared to controls (p<0.05). Serum TGF-β1 levels in AD patients were significantly lower than those in controls (p<0.05). There was a negative correlation between serum VEGF/TGF-β1 levels and the Clinical Dementia Rating (CDR) scores (p<0.05) and a positive correlation between serum VEGF levels and TGF-β1 levels (p<0.05). These observations suggest that angiogenesis might be involved in the onset process of AD and the decrease of angiogenic factors might be related to the severity of cognitive impairment., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Analysis of serum brain-derived neurotrophic factor (BDNF) levels in Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI) and controls with BDNF gene polymorphism and cognitive function were investigated. The study recruited 63 AD patients, 15 aMCI and 63 age- and sex-matched healthy controls from All India Institute of Medical Sciences, New Delhi, India. Patients with AD (12268.3 ± 7099.9 pg BDNF/ml) and aMCI (10780 ± 4184.2 pg BDNF/ml) had higher serum levels than had the controls (9362.833 ± 5883.32 pg BDNF/ml). Significant difference in BDNF levels was not found between the three groups. No significant difference was obtained between BDNF genotype and allele distribution between AD patients, aMCI versus controls; genotypic frequency: Chi-square = 3.21; p-value = 0.20 and allelic frequency: Chi-square = 0.412, p-value = 0.521, df = 1 (AD vs controls); Chi-square = 1.63, p-value = 0.201, df = 1 (aMCI vs controls). In conclusion, val66met polymorphism and BDNF serum level between the three groups and genotype did not significantly affect the serum BDNF level or age, Mini-Mental State Examination score in AD and aMCI. Further studies are necessary to elucidate the kinetics and the potential role of serum BDNF as a marker of disease progression in AD patients.

Objective: To evaluate the utility of near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) parameters as potential markers for amnestic mild cognitive impairment (aMCI)., Methods: By means of NIRS and TCD, noninvasive and inexpensive technologies, we studied 21 patients with aMCI (10 M and 11 F, 70.2 ± 7.3 years) and 10 age matched healthy controls., Results: By means of NIRS, we found a significant mean decrease of tissue oxygen saturation of cortex microcirculation (TOI), - 27%, p < 0.0005, on the temporal-parietal cortex of both side compared to the controls. By means of TCD, we found a significant mean increase of pulsatility index (PI), p < 0.0007, of middle cerebral artery (MCA) of both side compared to the controls. Cerebrovascular risk factors were present in 81% of the aMCI patients., Conclusions: Our study reveals that the TOI reduction on the temporal-parietal cortex of both side and the increase of PI in both MCA are associated with a clinical diagnosis of aMCI patients., Significance: The reduction of TOI may be considered a new marker for aMCI, especially when combined with the increase of PI in MCA., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions., Methodology/principal Findings: Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05)., Conclusions/significance: The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI., Trial Registration: UMIN-CTR UMIN000003662 ctr.cgi&quest;function&hairsp;&equals;&hairsp;brows&action&hairsp;&equals;&hairsp;brows&type&hairsp;&equals;&hairsp;summary&recptno&hairsp;&equals;&hairsp;R000004436&language&hairsp;&equals;&hairsp;J.

Objective: Alterations of the immune system play important roles in Alzheimer's disease (AD). The primary purpose of this study was to compare the plasma levels of neopterin, a marker of cellular immune activity, in amnestic mild cognitive impairment (aMCI), early (mild to moderate) AD, and cognitively normal controls. In addition, the correlation of plasma neopterin with interferon-gamma (IFN-γ) and interleukin-6 (IL-6) was also examined., Methods: Plasma samples from patients with mild-to-moderate AD (N = 34), aMCI (N = 27), and cognitively normal controls (N = 30) were obtained from the Johns Hopkins Alzheimer's Disease Research Center. Plasma neopterin, IFN-γ, and IL-6 levels were measured using commercially available ELISAs. Multiple linear regression was performed to study differences in the baseline neopterin levels between normal, aMCI, and AD patients. Pearson correlation coefficients were estimated for neopterin and IFN-γ and IL-6 levels. All analyses were conducted using SAS (SAS Institute, Inc., Cary, NC) and GraphPad Prism version 5.00 for Window (GraphPad Software, San Diego, CA, USA)., Results: AD subjects had significantly higher neopterin values compared with aMCI (β = 0.202, p = 0.004) and normal (β = 0.263, p = 0.0004) subjects. There was no statistically significant difference between normal and aMCI subjects. Significant associations between neopterin and IFN-γ (r = 0.41, p < 0.0001) and IL-6 (r = 0.35, p = 0.0006) levels were found., Conclusions: Our study demonstrates that peripheral immune response may be stronger in later stages of AD pathophysiology, when dementia has developed., (Copyright © 2012 John Wiley & Sons, Ltd.)

Polyunsaturated fatty acids (PUFA) of the n-3 series have been linked to brain physiology and cognitive decline, but little is known about the other components of the complex fatty acids category. Here, we compared 30 molecular species pertaining to saturated, monounsaturated, polyunsaturated, and trans fatty acids, measured in plasma by gas chromatography, in 14 patients with a diagnosis of amnestic single domain mild cognitive impairment (aMCI), 30 patients with mild Alzheimer's disease (AD), and 30 healthy controls (HC). As no participants showed neuroimaging evidence of cerebrovascular disease, patients could be considered as purely neurodegenerative. We found differences in specific components of almost all fatty acid classes except n-3-polyunsaturated fatty acids. Compared with HC, aMCI and AD patients had higher levels of arachidic (C20:0), erucic (C22:1, n-9), and vaccenic acid (C18:1, n-9) and lower levels of cerotic (C26:0) and linoleic acid (C18:2, n-6). In particular, level of linoleic acid decreased and level of mead acid increased progressively from HC to aMCI to AD patients, and they were also inversely correlated in AD and aMCI patients. In conclusion, we found a previously unrecognized linoleic acid deficiency in the early phase of neurodegeneration that was strongly supported by an increased, compensatory mead acid level. These findings suggest the importance of creating new dietary manipulation strategies to counteract disease progression.

The relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and serum ACE activity, as well as amnestic mild cognitive impairment (aMCI), was investigated. The study recruited 90 aMCI patients and 90 matched healthy controls. All subjects underwent an extensive assessment of cognitive function. The ACE gene I/D genotype was determined by polymerase chain reaction. Serum ACE activity was measured using a spectrophotometric technique. The scores obtained by the aMCI patients on the neuropsychological tests were significantly lower than those of the control subjects (all p<0.01). The genotype (χ(2)=11.510) and allele (χ(2)=6.945) frequencies of the ACE gene were significantly different between the aMCI and the control groups (all p<0.01). The DD genotype (23%) and D-allele (57%) frequencies in the aMCI patients were higher than those in the controls (16% vs. 43%). ACE genotype was correlated with delayed recall in Auditory Verbal Memory Test, delayed recall in Complex Figure Test, Category Fluency Test, and Symbol Digit Modalities Test in all subjects, in which the carriers of the DD and DI genotypes obtained lower scores than those of the II genotype (p<0.05). A significant difference in the serum ACE level was observed among the three genotypes (DD>DI>II) in both the aMCI and the control groups (all p<0.01). D-allele may be a genetic risk factor for the development of aMCI to Alzheimer's disease. A high serum ACE level possibly plays an important role in the incidence of aMCI., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Early diagnosis of Alzheimer's disease (AD) is important for initiating timely therapy to block or slow the rate of disease progression. This study was designed to investigate the potential of inflammation-related biomarkers in peripheral blood to accurately reflect AD onset and progression. Individuals (n=150) with amnestic mild cognitive impairment (aMCI) were divided into two subgroups (low- and high-risk) based on APOEε4 allele carrier status, and administered a battery of neuropsychological tests and tested for serum levels of IL-6, IL-10, TNF-α, and IFN-γ by using specific enzyme-linked immunosorbent assays. Results were compared with those from age-matched healthy controls (n=150). The levels of IL-6 were significantly higher in the aMCI group than in controls (P<0.01). When the aMCI group was stratified by APOEε4 status, significant differences were found between the low- and high-risk groups and controls in the levels of IL-6 and IFN-γ (P<0.01 and P=0.041, respectively). Moreover, the IL-6 level in the low-risk aMCI group was higher than that in the high-risk aMCI group (P=0.028). A weak but significant negative correlation was found between IL-6 and cognitive performance. Taken together, these findings indicate that IL-6, while not useful alone, has potential in combination with other biomarkers to support early diagnosis of aMCI due to its association with the progression of cognitive impairment., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare the effects of a 4-week high-saturated fat/high-glycemic index (HIGH) diet with a low-saturated fat/low-glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI)., Design: Randomized controlled trial., Setting: Veterans Affairs Medical Center clinical research unit., Participants: Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years)., Intervention: Participants received the HIGH diet (fat, 45% [saturated fat, > 25%]; carbohydrates, 35%-40% [glycemic index, > 70]; and protein, 15%-20%) or the LOW diet (fat, 25%; [saturated fat, < 7%]; carbohydrates, 55%-60% [glycemic index, < 55]; and protein, 15%-20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet., Main Outcome Measures: The CSF concentrations of β-amyloid (Aβ42 and Aβ40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition., Results: For the aMCI group, the LOW diet increased CSF Aβ42 concentrations, contrary to the pathologic pattern of lowered CSF Aβ42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF Aβ42, whereas the HIGH diet increased CSF Aβ42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet., Conclusion: Our results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of Aβ42, lipoproteins, oxidative stress, and insulin.

To characterize the correlates of cognitive function, serum concentrations of angiotensin converting enzyme (ACE) and brain structure with the ACE insertion or deletion (I/D) polymorphism were analyzed in subjects with amnestic-mild cognitive impairment (aMCI). A group of 48 subjects meeting criteria for aMCI and 36 age-matched control subjects were assessed using a comprehensive battery of standardized neuropsychological tests and magnetic resonance imaging (MRI). The ACE gene's I/D polymorphism was analyzed by means of PCR, and serum ACE concentrations were measured using ultraviolet spectrophotometry. Genotype effects on neuropsychological domains and MRI gray matter volume (GMV) measurements (optimized voxel-based morphometry) were examined using general linear models. The D carriers among the aMCI subjects performed significantly worse on AVLT-delayed recall compared to the I homozygous group. The D carriers had higher serum ACE concentrations than did the I homozygous carriers, though this difference only reached statistical significance in the aMCI group. Compared with the I homozygous carriers, in the aMCI group, D carriers showed smaller GMV of the bilateral middle frontal gyrus, right cuneus, right precentral gyrus, right medial frontal gyrus, right superior frontal gyrus, and left postcentral gyrus. However, there was no significant difference in GMV between I homozygous and D carriers in the normal control group. The study suggests that ACE genotype has considerable effect on the cognitive performance of aMCI subjects, particularly episodic memory, serum activity of ACE, and the structure of specified brain regions. The ACE D allele may be a genetic risk factor for greater atrophy of gray matter in aMCI., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: The enigma of Traumatic Brain Injury (TBI), reflected in recent scientific literature, is its uncertain consequences, variability of the final prognosis with apparently similar TBI, necessity for peripheral biomarkers, and more specific predictive models., Objectives: To study the relationship between serum S100B and survival in TBI patients in various serious situations; the S100B level in patients without traumatic pathology or associated tumour, subjected to stressful situations such as neurological intensive care unit (NICU) stay; the possible overestimation caused by extracerebral liberation in TBI patients and associated polytraumatism; the predictive cutoffs to determine the most sensitive and specific chronology; and achieve a predictive prognostic model., Methods: Patients admitted to the NICU within 6 hours after TBI were selected. We measured: a) clinical: exitus yes/no; age and gender, traumatic mechanism, polytraumatism yes/no, GCS score, unconsciousness duration, amnesia duration, neurological focality, and surgical interventions; b) radiological: CT scan for radiological lesions; c) biochemical: serum SB100B at 6, 24, 48 and 72 hours after TBI and drug abuse detected in the urine; d) GOS on hospital discharge., Results: N: 149 TBI patients, independent of polytraumatism, mean serum S100B at 6, 24, 48, and 72 hours: 2.1, 1.3, 1.2, and 0.6 microg/L, respectively; N: 124 without associated polytraumatism, S100B at 6, 24, 48, and 72 hours: 2.0, 1.4, 1.3, and 0.6 microg/L; N: 50 control I S100B 24 hours: 0.17 microg/L (0.04 - 0.56) and 25 healthy subjects S100B 0.057 microg/L (0.02-0.094)., Conclusions: Significantly higher S100B levels are observed on exitus, with excellent TBI prognosis and evolution performance. Hospital stay in the NICU produces significant increases in S100B compared to healthy subjects, without invalidating it as a biomarker. Polytraumatism associated to TBI does not significantly alter S100B levels. S100B at 24 hours > or = 0.90 microg/L appears to predict unfavourable TBI evolution with a NPV: 94.2% and PPV: 54.9%. We propose a predictive model when we associate S100B at 24 hours with amnesia duration over 30 minutes with a NPV of 85.5% and a PPV of 83.3%.

Objective: To develop a blood-based test for screening populations at risk for Alzheimer disease., Design: Case-control study. Subjects A total of 180 patients with mild cognitive impairment (MCI) and 105 age-matched, cognitively normal controls., Interventions: The titer of beta-amyloid 1-42 autoantibodies in the plasma was obtained at the time of diagnosis and evaluated by enzyme-linked immunosorbent assay before and after dissociation of the antigen-antibody complexes. A total of 107 patients with MCI were followed up for 36 months; 70 of the 107 cases progressed to Alzheimer disease., Results: The average level of beta-amyloid 1-42 plasma autoantibodies in patients with MCI that progressed to Alzheimer disease, but not that of the stable cases, was significantly higher than in cognitively normal controls (P < .001)., Conclusions: The results suggest that the plasma beta-amyloid 1-42 autoantibodies parallel beta-amyloid 42 deposition in the brain, which is known to precede by several years the clinical onset of Alzheimer disease. The evaluation of beta-amyloid 1-42 autoantibodies after dissociation of the complexes is a simple and inexpensive method that can be used to predict the occurrence of Alzheimer disease.

Oxidative stress,which contributes to neuronal damage, is thought to be a pathophysiologicalmechanism of Alzheimer's disease (AD). Markers of oxidative stress may appear early in the preclinical, mild cognitive impairment (MCI) phase of AD.We investigated the interaction among enzymatic-derived oxysterols (24S-hydroxycholesterol and 27-hydroxycholesterol), markers of oxidative stress, including free radical-related oxysterols (7 hydroxycholesterol and 7-ketocholesterol), and vitamin E in AD patients and two amnestic MCI subtypes, amnestic single-domain MCI (a-MCI) subjects, and multidomain MCI (md-MCI) subjects, compared to healthy control subjects (HC). The study included 37 patients with AD, 24 with a-MCI, 29 with md-MCI, and 24 HC. Plasma assessments were made using isotope dilution-mass spectrometry. Although we found no significant change in free radical- or enzymatic-derived oxysterol concentrations in AD or MCI patients, vitamin E levels corrected for cholesterol were reduced in AD patients compared to HC. Results suggest that AD patients have upregulated cerebral oxidative stress or a nutritional deficit of vitamin E. The oxysterols investigated here are not useful markers for diagnosing AD or MCI.

Background: Alterations in interrelated endocrine axes may be related to the pathogenesis of mild cognitive impairment (MCI) and dementia., Methods: Salivary cortisol before and after a 0.5-mg dexamethasone test, and serum levels of thyroid-stimulating hormone, total thyroxine (T(4)), free T(4), total triiodothyronine (TT(3)), estradiol, testosterone and insulin-like growth factor 1 were measured in 43 MCI cases and 26 healthy controls. All participants underwent a comprehensive neuropsychological test battery covering the cognitive domains of speed/attention, memory, visuospatial functions, language and executive functions., Results: The MCI group did not differ in basal levels of endocrine markers compared to controls. Among those with MCI, TT(3) levels were inversely associated with cognitive performance across all domains. After stratifying MCI cases according to TT(3) levels, those with relatively high TT(3) levels showed impairment in memory as well as in visuospatial and executive functions. Those with TT(3) levels at or below the lower boundary of the normal range performed comparably to healthy controls. Other endocrine markers were not related to cognitive performance., Conclusions: Among those with MCI, TT(3) was associated with a neuropsychological profile typical of prodromal Alzheimer's disease. While the mechanisms remain unclear, optimal levels of thyroid hormone under a compromising condition such as MCI and related neuropathology need reconsideration., (Copyright © 2010 S. Karger AG, Basel.)

A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (beta-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and beta-NGF may be useful in differentiating subtypes of MCI.

Background and Objective: There are conflicting data relating homocysteine levels to the risk of Alzheimer's disease (AD). We sought to explore whether fasting plasma homocysteine is associated with the risk of mild cognitive impairment (MCI), an intermediate stage to dementia., Methods: Fasting levels of plasma homocysteine were obtained from 678 elderly subjects chosen at random from a cohort of Medicare recipients. There were longitudinal data in 516 subjects without MCI or dementia at baseline who were followed for 2,705 person-years. The relation of plasma homocysteine with prevalent and incident all-cause MCI, amnestic MCI and non-amnestic MCI was assessed using logistic and Cox proportional hazards regression analyses., Results: There were 162 cases of prevalent MCI and 132 cases of incident MCI in 5.2 years of follow-up. There was no association between plasma homocysteine and prevalence of MCI or amnestic or non-amnestic MCI in the cross-sectional analyses. There was no association between higher homocysteine levels and a lower risk of all-cause MCI. Consistent with the cross-sectional analyses, there was no specific association with the amnestic or non-amnestic subtype of MCI in crude or adjusted models., Conclusion: Plasma homocysteine levels measured at baseline were not related to MCI or its subtypes in an elderly multiethnic cohort.

Amnestic mild cognitive impairment (aMCI) is considered a prodromal stage of Alzheimer's disease (AD). We measured plasma levels of amyloid-beta40 (Abeta40) and Abeta42 in 191 subjects with aMCI. Seventy-nine of them were clinically followed for two years. In the total cohort of aMCI cases, the average level of Abeta42, as well as the Abeta42/Abeta40 ratio, was significantly higher than those of the 102 cognitively normal age-matched subjects. The aMCI cases that converted to probable AD within 2 years had higher levels of Abeta42 and, to a lesser extent, Abeta40 than the stable cases. However the large variability of measured values indicates that plasma Abeta is not a suitable marker of incipient AD.

Background/aims: To investigate the association between cortisol levels, chronic stress and coping in subjects with amnestic-type mild cognitive impairment (aMCI)., Methods: Cortisol levels were measured using morning saliva samples from 33 individuals with aMCI and from 41 healthy elderly. Chronic stress was evaluated with the Stress Symptoms List (SSL), whereas coping strategies were assessed using the Jalowiec Coping Scale., Results: aMCI subjects with high SSL scores presented higher cortisol levels (p = 0.045). Furthermore, aMCI subjects who employed emotion-focused coping had higher SSL scores (p = 0.023)., Conclusion: The association between increased cortisol secretion, chronic stress and coping strategies may be modulated by the presence or absence of cognitive impairment, where memory defi- cit awareness constitutes an additional potential factor involved in high stress severity., (Copyright 2009 S. Karger AG, Basel.)

Objective: Experimental and clinical data suggested that brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is characterized by declined cognitive function and has a high probability of evolving into AD. The aim of this study was to investigate serum BDNF concentrations in aMCI patients and determine whether there is an association of the BDNF gene Val66Met polymorphism with aMCI, cognitive function, and serum BDNF., Method: Between April 2005 and January 2006, the present study recruited 99 aMCI patients who met diagnostic criteria for MCI proposed by the Mayo Clinic Alzheimer's Disease Research Center and 99 matched healthy controls from a population-based sample. All subjects underwent extensive assessment of cognitive function, measurement of serum BDNF by an enzyme-linked immunosorbent assay, and genotyping of the BDNF gene Val66Met polymorphism., Results: The serum concentrations of BDNF in aMCI patients (median [interquartile range] = 4.37 [2.35-6.40] ng/mL) were significantly lower than those of healthy controls (4.98 [3.50-7.33] ng/mL) (z = -2.449, p = .014). There were significant positive correlations between serum BDNF and scores on delayed recall in the Auditory Verbal Learning Test, which reflects episodic memory (r = 0.264, p = .008). No significant differences were found for either the genotype or allele distribution of BDNF Val66Met polymorphism between aMCI patients and control subjects. The BDNF Val66Met polymorphism was not associated with serum BDNF or cognitive function in aMCI patients., Conclusions: This study suggests that reduced BDNF levels may play a role in the pathophysiology of aMCI, and the BDNF gene Val66Met polymorphism may not be an important factor in susceptibility to aMCI.

Objective: To investigate the relationship between serum brain-derived neurotrophic factor, concentrations and BDNF gene Val66Met polymorphism and amnestic mild cognitive impairment (aMCI), and neuropsychological characteristics., Methods: Ninety-nine aMCI patients and 99 matched normal controls were recruited for the study. Multi-dimension neuropsychologic tests were used to extensively assess the cognitive function, an enzyme-linked immunosorbent assay was applied to measure serum BDNF concentrations, and polymerase chain reaction-restriction fragment length polymorphism was used to analyse BDNF gene Val66Met polymorphism in the subjects., Results: The scores of neuropsychologic tests in aMCI patients were significantly lower than those in the normal controls (all P<0.001), with the largest impairment on delayed recall of the auditory verbal memory test (AVMT) which reflect verbal episodic memory. The serum concentrations of BDNF in aMCI patients (median: 4.37 microg/L) were significantly lower than those of the normal controls (median: 4.98 microg/L) (z=-2.449, P=0.014). There was positive correlation between the serum concentrations of BDNF and the scores on delayed recall of AVMT (r=0.264, P=0.008). No significant differences were found for the genotype and allele distribution of BDNF Val66Met polymorphism between aMCI patients and the normal controls. BDNF Val66Met polymorphism was not associated with serum BDNF concentrations and cognitive assessment scores in aMCI patients (P>0.05)., Conclusion: aMCI is characterized by episodic memory impairment. Decreased BDNF concentrations may play a role in the pathophysiology of aMCI, and BDNF gene Val66Met polymorphism may not be an important genetic factor in susceptibility to aMCI.

Coated-platelets, a subset of platelets produced by coactivation with both collagen and thrombin, retain intact amyloid precursor protein on their surface. We analyzed blood samples from 66 individuals with mild cognitive impairment (36 amnestic and 30 nonamnestic) for coated-platelet production. Coated-platelet levels were significantly higher in amnestic compared with nonamnestic patients (P=0.037). These findings support the hypothesis that coated-platelets may be linked to the requisite alteration in amyloid precursor protein metabolism that occurs in Alzheimer disease.

Primary Objective: To examine the relationship between serum concentrations of protein S-100beta and neuropsychological functioning following severe traumatic brain injury., Design: Matched control group., Methods: Blood samples were taken within 12 hours of injury and then daily up to 7 days post-injury (n=23). Within 2 weeks of emerging from post-traumatic amnesia (PTA), participants completed a battery of neuropsychological measures. These results were compared with a matched sample of healthy controls., Results: Early measurement of S-100 not only reflected overall brain injury severity, but also related to neuropsychological deficits, with higher serum concentrations associated with poorer performance across most cognitive domains. PTA duration, measured by the Westmead PTA Scale, was found to be the strongest predictor of S-100 concentration (R2=0.59, p<0.001)., Conclusions: These findings show that measurement of serum protein S-100 may further aid in the identification of individuals with severe TBI who are likely to experience cognitive difficulties.

Objective: The authors investigated the frequency distribution of well-established risk factors for dementia--high plasma homocysteine and the apolipoprotein E epsilon4 allele (APOE epsilon4)--among older women with subjective memory complaints (SMC) but no cognitive impairment, and with mild cognitive impairment (MCI)., Methods: This was a cross-sectional, community-based study., Results: Women with MCI had higher total plasma homocysteine than healthy-comparison subjects. There was also a nonsignificant excess of APOE epsilon4 carriers in the MCI than in the healthy group. Participants with SMC had higher depression and anxiety scores than healthy-comparison subjects, but did not differ from subjects in the healthy-comparison group in relation to their total plasma homocysteine and APOE epsilon4 distribution., Conclusions: MCI seems to be more closely related to well-established risk factors for dementia than is SMC.

To assess whether platelets are activated in transient global amnesia (TGA) and TIA, blood samples were analyzed by fluorescence-activated cytoscan using antibodies specific for platelet fibrinogen receptor (PAC1) and P-selectin (CD62P). Samples from TIA contained high levels of CD62P compared with age-matched control subjects, whereas those from TGA did not. The authors suggest that activated platelets are involved in brain ischemia, whereas ischemia appears not to be associated with most TGA.