Association between internal carotid artery kinking and ischemic stroke: A population-based cross-sectional study.

AIM: Evidence for an association between Internal carotid artery (ICA) kinking and ischemic stroke has been controversial. We aimed to examine the association between ICA tortuosity and risk of ischemic stroke and specific ischemic stroke subtypes (large artery atherosclerosis, LAA; small artery occlusion, SAO). METHODS: A total of 419 outpatients were included in this cross-sectional study. ICA kinking was objectively assessed by head and neck computed tomography angiography (CTA). The risk of ischemic stroke for each patient was evaluated according to the Essen Stroke Risk Score (ESRS). Ischemic stroke subtypes (LAA and SAO) were measure with head magnetic resonance imaging (MRI). RESULTS: The average age of patients was 59.1 years (SD = 13.25) and 264 (63.0 %) were males. The prevalence of ICA kinking in this sample was 31.5 % (132 out of 419). Individuals with ICA kinking was associated with 0.55-points increase in ESRS score than those without ICA kinking (95 % CI, 0.28-0.81, p < 0.001) among patients over 50 years. In addition, right ICA kinking or left ICA kinking were associated with 0.35-points (95 % CI, 0.08-0.63) and 0.49-points (95 % CI, 0.23-0.76) increase in ESRS score, respectively. For specific ischemic stroke subtypes, individuals with ICA kinking had a 10.34-fold increased risk of SAO compared to those without ICA kinking (95 % CI, 6.22-20.68). Individuals with right ICA kinking had a 4.51-fold risk of SAO than those without kinking (95 % CI, 2.64-7.71), and had an 8.86-fold risk of SAO than those without kinking in the left ICA kinking (95 % CI, 4.97-15.79). CONCLUSION: Our findings support the role of ICA kinking on ischemic stroke. Early screening and proper treatment of carotid artery tortuosity could be a potential intervention strategy for the prevention of ischemic stroke later on.

Effect of High Cholesterol Regulation of LRP1 and RAGE on Aß Transport Across the Blood-Brain Barrier in Alzheimer's Disease.

BACKGROUND: High cholesterol aggravates the risk development of Alzheimer's disease (AD). AD is closely related to the transport impairment of Amyloid-ß (Aß) in the blood-brain barrier. It is unclear whether high cholesterol affects the risk of cognitive impairment in AD by affecting Aß transport. The purpose of the study is to investigate whether high cholesterol regulates Aß transport through low-density Lipoprotein Receptor-Related Protein 1 (LRP1) and Receptor for Advanced Glycation End products (RAGE) in the risk development of AD. METHODS: We established high cholesterol AD mice model. The learning and memory functions were evaluated by Morris Water Maze (MWM). Cerebral microvascular endothelial cells were isolated, cultured, and observed. The expression levels of LRP1 and RAGE of endothelial cells and their effect on Aß transport in vivo were observed. The expression level of LRP1 and RAGE was detected in cultured microvessels after using Wnt inhibitor DKK-1 and ß-catenin inhibitor XAV-939. RESULTS: Hypercholesterolemia exacerbated spatial learning and memory impairment. Hypercholesterolemia increased serum Aß40 level, while serum Aß42 level did not change significantly. Hypercholesterolemia decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells. Hypercholesterolemia increased brain apoptosis in AD mice. In in vitro experiment, high cholesterol decreased LRP1 expression and increased RAGE expression, increased Aß40 expression in cerebral microvascular endothelial cells. High cholesterol regulated the expressions of LRP1 and RAGE and transcriptional activity of LRP1 and RAGE promoters by the Wnt/ß-catenin signaling pathway. CONCLUSION: High cholesterol decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells, which led to Aß transport disorder in the blood-brain barrier. Increased Aß deposition in the brain aggravated apoptosis in the brain, resulting to cognitive impairment of AD mice.

Association of naturally occurring antibodies to ß-amyloid with cognitive decline and cerebral amyloidosis in Alzheimer's disease.

The pathological relevance of naturally occurring antibodies to ß-amyloid (NAbs-Aß) in Alzheimer's disease (AD) remains unclear. We aimed to investigate their levels and associations with Aß burden and cognitive decline in AD in a cross-sectional cohort from China and a longitudinal cohort from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. NAbs-Aß levels in plasma and cerebrospinal fluid (CSF) were tested according to their epitopes. Levels of NAbs targeting the amino terminus of Aß increased, and those targeting the mid-domain of Aß decreased in both CSF and plasma in AD patients. Higher plasma levels of NAbs targeting the amino terminus of Aß and lower plasma levels of NAbs targeting the mid-domain of Aß were associated with higher brain amyloidosis at baseline and faster cognitive decline during follow-up. Our findings suggest a dynamic response of the adaptive immune system in the progression of AD and are relevant to current passive immunotherapeutic strategies.

Blood cell-produced amyloid-ß induces cerebral Alzheimer-type pathologies and behavioral deficits.

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer's disease-type pathology and cognitive deficits in APP/PS1 mice.

Alzheimer's disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aß) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aß burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aß generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.

Brain Amyloid-ß Deposition and Blood Biomarkers in Patients with Clinically Diagnosed Alzheimer's Disease.

Brain amyloid-ß (Aß) deposition is a hallmark to define Alzheimer's disease (AD). We investigated the positive rate of brain amyloid deposition assessed with 11C-Pittsburgh compound (PiB)-PET and blood Aß levels in a cohort of probable AD patients who were diagnosed according to the 1984 NINCDS-ADRDA criteria. Eighty-four subjects with a clinical diagnosis of probable AD dementia, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) status were subjected to PiB-PET and 18F-fluorodeoxyglucose (FDG)-PET scans. Plasma biomarkers of Aß42, Aß40, and T-tau were measured using single molecule array technology. The positive rate of PiB-PET, the associations between PiB-PET status and FDG-PET, plasma biomarkers, and clinical manifestations were analyzed. PiB-PET was positive in 77.36% of probable AD patients, 31.80% of MCI patients, and 0 of NC. Plasma Aß42/Aß40 ratio was associated with PiB-PET, the ROC curve analysis revealing an AUC of 0.77 (95% CI: 0.66-0.87), with a sensitivity of 82% and specificity of 64%. Some clinical manifestations were associated with PiB-PET imaging. Our findings indicate that only three-fourths of patients diagnosed with probable AD fit the pathological criteria, suggesting that we should be cautious regarding the accuracy of AD diagnosis when no biomarker evidence is available in our clinical practice.

LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer's Disease - Related Pathology.

Polymorphism of the cholesterol-24S-hydroxylase (CYP46A1) gene is thought to be a risk factor for Alzheimer's disease (AD). A single nucleotide polymorphism (T/C) in intron 2, rs754203, has been confirmed to be implicated in AD. Rs754203 is located in the long intronic non-coding RNA (LincRNA) sequence, which has previously been shown to be involved in the pathology of many diseases. Thus, the present study aimed to investigate the role of LincRNA in the CYP46A1 gene expression and related AD pathology. SH-SY5Y cells with overexpressed TT or CC genotype CYP46A1 were used. Through RT-PCR, Western blot and ELISA assays, we found that LincRNA can affect the CYP46A1 gene expression and the production of 24-OHC and Aß. Overexpression of LincRNA can significantly inhibit CYP46A1 expression and 24-OHC production, as well as increasing the Aß expression level. Silencing of LincRNA confirmed the role that it plays in the regulation of CYP46A1, as well as the production of 24-OHC and Aß. In addition, this effect was stronger in the A type LincRNA than in the G type LincRNA. Results from dual luciferase assays show that LincRNA inhibited the activity of the CYP46A1 gene promoter. This study indicates a possible novel role of LincRNA and provides a new way to look into the relationship between CYP46A1 polymorphism and AD pathology. This may identify a novel pathway through which to explore AD therapy.

Physiological clearance of tau in the periphery and its therapeutic potential for tauopathies.

Accumulation of pathological tau is the hallmark of Alzheimer's disease and other tauopathies and is closely correlated with cognitive decline. Clearance of pathological tau from the brain is a major therapeutic strategy for tauopathies. The physiological capacity of the periphery to clear brain-derived tau and its therapeutic potential remain largely unknown. Here, we found that cisterna magna injected 131I-labelled synthetic tau dynamically effluxed from the brain and was mainly cleared from the kidney, blood, and liver in mice; we also found that plasma tau levels in inferior vena cava were lower than those in femoral artery in humans. These findings suggest that tau proteins can efflux out of the brain and be cleared in the periphery under physiological conditions. Next, we showed that lowering blood tau levels via peritoneal dialysis could reduce interstitial fluid (ISF) tau levels in the brain, and tau levels in the blood and ISF were dynamically correlated; furthermore, tau efflux from the brain was accelerated after the addition of another set of peripheral system in a parabiosis model. Finally, we established parabiosis mouse models using tau transgenic mice and their wild-type littermates and found that brain tau levels and related pathologies in parabiotic transgenic mice were significantly reduced after parabiosis, suggesting that chronic enhancement of peripheral tau clearance alleviates pathological tau accumulation and neurodegeneration in the brain. Our study provides the first evidence of physiological clearance of brain-derived pathological tau in the periphery, suggesting that enhancing peripheral tau clearance is a potential therapeutic strategy for tauopathies.

The ProNGF/p75NTR pathway induces tau pathology and is a therapeutic target for FTLD-tau.

Tau pathology is characterized as a form of frontotemporal lobar degeneration (FTLD) known as FTLD-tau. The underlying pathogenic mechanisms are not known and no therapeutic interventions are currently available. Here, we report that the neurotrophin receptor p75NTR plays a critical role in the pathogenesis of FTLD-tau. The expression of p75NTR and the precursor of nerve growth factor (proNGF) were increased in the brains of FTLD-tau patients and mice (P301L transgenic). ProNGF-induced tau phosphorylation via p75NTR in vitro, which was associated with the AKT/glycogen synthase kinase (GSK)3ß pathway. Genetic reduction of p75NTR in P301L mice rescued the memory deficits, alleviated tau hyperphosphorylation and restored the activity of the AKT/GSK3ß pathway. Treatment of the P301L mice with the soluble p75NTR extracellular domain (p75ECD-Fc), which can antagonize neurotoxic ligands of p75NTR, effectively improved memory behavior and suppressed tau pathology. This suggests that p75NTR plays a crucial role in tau paGSKthology and represents a potential druggable target for FTLD-tau and related tauopathies.

Gut Microbiota is Altered in Patients with Alzheimer's Disease.

Previous studies suggest that gut microbiota is associated with neuropsychiatric disorders, such as Parkinson's disease, amyotrophic lateral sclerosis, and depression. However, whether the composition and diversity of gut microbiota is altered in patients with Alzheimer's disease (AD) remains largely unknown. In the present study, we collected fecal samples from 43 AD patients and 43 age- and gender-matched cognitively normal controls. 16S ribosomal RNA sequencing technique was used to analyze the microbiota composition in feces. The composition of gut microbiota was different between the two groups. Several bacteria taxa in AD patients were different from those in controls at taxonomic levels, such as Bacteroides, Actinobacteria, Ruminococcus, Lachnospiraceae, and Selenomonadales. Our findings suggest that gut microbiota is altered in AD patients and may be involved in the pathogenesis of AD.

CYP46A1 and the APOEε4 Allele Polymorphisms Correlate with the Risk of Alzheimer's Disease.

Polymorphisms of the cholesterol-24S-hydroxylase (CYP46A1) and apolipoprotein E (APOE) genes are risk factors for Alzheimer's disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (Aß) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and Aß levels and AD risk. We found that the APOEε4 alleles were significantly higher in patients with AD and there was a potential synergistic interaction between the CYP46A1 C allele and APOEε4 allele in AD. Blood 24-OHC level and Aß level were significantly higher in AD patients than controls, indicating 24-OHC could be a marker in AD diagnosis. However, AD patients with the CYP46A1 TT, but not CC, genotype had higher 24-OHC levels, which indicated that there may be other mechanisms in the relationship between CYP46A1 polymorphisms and AD.

Concomitant Asymptomatic Intracranial Atherosclerotic Stenosis Increase the 30-Day Risk of Stroke in Patients Undergoing Symptomatic Intracranial Atherosclerotic Stenosis Stenting.

BACKGROUND: In the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, 19.1% of ischemic strokes occurred out of the territory of previously symptomatic stenosis during the mean follow-up period of 23.4 months. However, it is unknown how many ischemic strokes were due to a previously asymptomatic intracranial atherosclerotic stenosis (ICAS). The objective of this study was to investigate whether the concomitant asymptomatic ICAS influences the outcome of patients undergoing symptomatic ICAS stenting. METHODS: We retrospectively reviewed 576 consecutive patients with nondisabling ischemic stroke (modified Rankin scale score of ≤3) who were treated with symptomatic ICAS (≥70% stenosis) stenting with or without concomitant asymptomatic ICAS. The baseline characteristics and the 30-day primary end points (stroke or death after stenting) were compared by bivariate and multivariable logistic analyses. RESULTS: The 30-day rate of primary end points was 5.2%, which was higher in patients with concomitant asymptomatic ICAS (≥50% stenosis) than in those without asymptomatic ICAS (no stenosis or <50% stenosis) (8.9% versus 3.8%, P = .014). In patients with concomitant asymptomatic ICAS, 25% of ischemic strokes occurred out of the territory of the stented artery, whereas in patients without asymptomatic ICAS, no ischemic stroke occurred out of the territory of the stented artery. Multivariable analysis showed that concomitant asymptomatic ICAS was an independent risk factor for 30-day stroke (odds ratio = 2.37, 95% confidence interval, 1.14-5.63; P = .023). CONCLUSIONS: Concomitant asymptomatic ICAS (≥50% stenosis) might increase the 30-day risk of stroke in patients undergoing symptomatic ICAS stenting.

Comorbidity Burden of Dementia: A Hospital-Based Retrospective Study from 2003 to 2012 in Seven Cities in China.

Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden of dementia patients in China at the national level, we enrolled 2,938 patients with Alzheimer's disease (AD), vascular dementia (VaD), or other types of dementia, who were admitted to tertiary hospitals in seven regions of China from January 2003 to December 2012. The Charlson Comorbidity Index (CCI) was used to evaluate the comorbidity burden of the patients with dementia. Among these patients, 53.4% had AD, 26.3% had VaD, and 20.3% had other types of dementia. The CCI was 3.0 ± 1.9 for all patients, 3.4 ± 1.8 for those with VaD, and 3.0 ± 2.1 for those with AD. The CCI increased with age in all patients, and the length of hospital stay and daily expenses rose with age and CCI. Males had a higher CCI and a longer stay than females. Moreover, patients admitted in the last 5 years of the study had a higher CCI than those admitted in the first 5 years. We found that the comorbidity burden of patients with dementia is heavy. These findings provide a better understanding of the overall health status of dementia patients, and help to increase the awareness of clinicians and policy-makers to improve medical care for patients.

Comorbidity burden of patients with Parkinson's disease and Parkinsonism between 2003 and 2012: A multicentre, nationwide, retrospective study in China.

Parkinson's disease (PD) and Parkinsonism are common neurodegenerative disorders with continuously increasing prevalence, causing high global burdens. However, data concerning the comorbidity burden of patients with PD or Parkinsonism in China are lacking. To investigate the health condition and comorbidity burden, a total of 3367 PD and 823 Parkinsonism patients were included from seven tertiary hospitals in seven cities across China from 2003 to 2012. Their comorbidity burden was collected and quantified by the Elixhauser Comorbidity Index (ECI) and Charlson Comorbidity Index (CCI). The comorbidity spectra differed between PD and Parkinsonism patients. Compared with PD patients, Parkinsonism patients were older (69.8 ± 11.5 vs. 67.9 ± 11.4, P < 0.001); had a higher comorbidity burden, including ECI (1.1 ± 1.2 vs. 1.0 ± 1.2, P < 0.001) and CCI (1.3 ± 1.6 vs. 1.1 ± 1.5, P < 0.001); and had higher hospitalization expenses. The ECI (1.1 ± 1.3 vs. 0.9 ± 1.1, P < 0.001) and CCI (1.3 ± 1.6 vs. 0.9 ± 1.2, P < 0.001) were higher in males than in females. The average length of stay and daily hospitalization expenses increased with age, as did ECI and CCI. This is the first study to report the disease burden of Chinese PD and Parkinsonism patients. It provides useful information to better understand their health status, and to raise the awareness of clinicians for providing better health care.

Peritoneal dialysis reduces amyloid-beta plasma levels in humans and attenuates Alzheimer-associated phenotypes in an APP/PS1 mouse model.

Clearance of amyloid-beta (Aß) from the brain is an important therapeutic strategy for Alzheimer's disease (AD). Current studies mainly focus on the central approach of Aß clearance by introducing therapeutic agents into the brain. In a previous study, we found that peripheral tissues and organs play important roles in clearing brain-derived Aß, suggesting that the peripheral approach of removing Aß from the blood may also be effective for AD therapy. Here, we investigated whether peritoneal dialysis, a clinically available therapeutic method for chronic kidney disease (CKD), reduces brain Aß burden and attenuates AD-type pathologies and cognitive impairments. Thirty patients with newly diagnosed CKD were enrolled. The plasma Aß concentrations of the patients were measured before and after peritoneal dialysis. APP/PS1 mice were subjected to peritoneal dialysis once a day for 1 month from 6 months of age (prevention study) or 9 months of age (treatment study). The Aß in the interstitial fluid (ISF) was collected using microdialysis. Behavioural performance, long-term potentiation (LTP), Aß burden and other AD-type pathologies were measured after 1 month of peritoneal dialysis. Peritoneal dialysis significantly reduced plasma Aß levels in both CKD patients and APP/PS1 mice. Aß levels in the brain ISF of APP/PS1 mice immediately decreased after reduction of Aß in the blood during peritoneal dialysis. In both prevention and treatment studies, peritoneal dialysis substantially reduced Aß deposition, attenuated other AD-type pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, and synaptic dysfunction, and rescued the behavioural deficits of APPswe/PS1 mice. Importantly, the Aß phagocytosis function of microglia was enhanced in APP/PS1 mice after peritoneal dialysis. Our study suggests that peritoneal dialysis is a promising therapeutic method for AD, and Aß clearance using a peripheral approach could be a desirable therapeutic strategy for AD.

Altered peripheral profile of blood cells in Alzheimer disease: A hospital-based case-control study.

Alzheimer disease (AD) has been made a global priority for its multifactorial pathogenesis and lack of disease-modifying therapies. We sought to investigate the changes of profile of blood routine in AD and its correlation with the disease severity.In all, 92 AD patients and 84 age and sex-matched normal controls were enrolled and their profiles of blood routine were evaluated.Alzheimer disease patients had increased levels of mean corpuscular hemoglobin, mean corpuscular volume, red cell distribution width-standard deviation, mean platelet volume,and decreased levels of platelet distribution width, red blood cell, hematocrit, hemoglobin, lymphocyte, and basophil compared with normal controls.Alterations in quantity and quality of blood cells may be involved in the pathogenesis of AD and contribute to the disease progression.

Reduced Cardiovascular Functions in Patients with Alzheimer's Disease.

Previous studies have suggested that cardiovascular functions might play a critical role in Alzheimer's disease (AD) pathogenesis. However, the relationship among heart function, blood flow of cerebral vessels, and AD remains unclear. In the present study, AD patients (n = 34) and age- and gender-matched cognitively normal controls (n = 34) were recruited. Demographic and comorbidity information was collected. The ejection fraction was measured using echocardiography, and the mean velocity, pulsatility index (PI), and resistance index (RI) of the basilar artery (BA), left terminal internal carotid artery (LTICA), and right terminal internal carotid artery (RTICA) were measured using transcranial Doppler. The data of lacunae, white matter changes, and plaques in the aortic arch and carotid arteries were collected from brain magnetic resonance imaging and computed tomography angiography images. Compared with normal controls, AD patients had lower ejection fractions and cerebral blood flow velocities and higher RI and PI in the BA, LTICA, and RTICA, as well as more plaques in the aortic and carotid arteries. In the multivariate logistic regression analysis, the ejection fraction and the mean velocity of the BA and LTICA were independently associated with AD after adjusting for age, gender, education, vascular risk factors, arterial plaques, and brain ischemic lesions detected in the brain images. These findings suggest that heart function and vascular condition may play important roles in AD pathogenesis. Improving cardiovascular functions could be a promising approach for the prevention and treatment of AD.

Associations Between Hepatic Functions and Plasma Amyloid-Beta Levels-Implications for the Capacity of Liver in Peripheral Amyloid-Beta Clearance.

Amyloid-beta (Aß) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Clearance of Aß is a promising therapeutic strategy for AD. We have previously demonstrated that peripheral organs play important roles in the clearance of brain-derived Aß. In the present study, we recruited 46 patients with liver cirrhosis and 46 normal controls and found that plasma Aß40 and Aß42 levels were significantly higher in the cirrhosis patients than in the normal controls. Notably, cirrhosis patients with hepatitis B virus (HBV) infection had higher plasma Aß40 and Aß42 levels than HBV-negative cirrhosis patients. Besides, cirrhosis patients had significantly higher plasma levels of interleukin-1ß (IL-1ß) and IL-6. Plasma tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) levels were not significantly different between the groups. Moreover, we found significant correlations of hepatic functions with plasma Aß40 and Aß42 levels. Plasma IL-6 levels were also significantly correlated with plasma Aß40 levels. However, in the linear regression model, we found significant correlation of plasma Aß40 levels with hepatic functions, but not with plasma IL-6 levels. Our results indicate that the hepatic dysfunctions might result in decreased peripheral Aß clearance by the liver. Protecting hepatic functions might be helpful for the clearance of brain-derived Aß in the blood.

Plasma Amyloid-Beta Levels in Patients with Different Types of Cancer.

Several epidemiological investigations indicate that cancer survivors have a lower risk for Alzheimer's disease (AD) and vice versa. However, the associations between plasma amyloid-beta (Aß) levels with cancer remain largely unknown. In this case-control study, 110 cancer patients, 70 AD patients, and 70 age- and gender-matched normal controls were recruited. The cancer types include esophagus cancer, colorectal cancer, hepatic cancer, and lung cancer, all of which were reported to be associated with a lower risk for AD. Plasma levels of Aß40, Aß42, common pro-inflammatory cytokines, IL-1ß, IL-6, TNF-α, IFN-γ, anti-inflammatory IL-4, chemokines, and cytokines MCP-1 were measured with enzyme-linked immunosorbent assay (ELISA) kits. Plasma levels of Aß40 and Aß42 in all cancer patients were higher than that in normal controls. More specifically, hepatic cancer patients exhibited significantly higher plasma Aß levels. No significant difference in plasma Aß levels was found between chemotherapy and no chemotherapy subgroups. Plasma Aß levels were not significantly correlated with pro-inflammatory cytokines, anti-inflammatory, chemokines, and cytokines. Peripheral Aß levels increased in cancer patients, especially in patients with hepatic cancer, independent of chemotherapy and inflammation. Further verification is required for the association between plasma Aß and cancer.

Association of dementia with death after ischemic stroke: A two-year prospective study.

The association between dementia and the risk of death after ischemic stroke was investigated. Neurological, neuropsychological and functional assessments were evaluated in 619 patients with acute ischemic stroke. Dementia was diagnosed at admission and at three months after stroke onset. The patients were scheduled for a two-year follow-up after the index stroke. The Kaplan-Meier survival and Cox proportional hazards regression analyses were used to estimate the cumulative proportion of survival, and the association between dementia and risk of death after stroke. In total, 146 patients (23.6%) were diagnosed with dementia after stroke. The cumulative proportion of surviving cases was 49.3% in patients with dementia after a median follow-up of 21.2±5.6 months, and 92.5% in patients without dementia. Multivariate analysis revealed that dementia (HR, 7.21; 95% CI, 3.85-13.49) was associated with death, independent of age, atrial fibrillation, previous stroke and NIH stroke scale. In conclusion, the mortality rate is increased in stroke patients with dementia. Dementia is an important risk factor for death after stroke, independent of age, atrial fibrillation, previous stroke, and the severity of the stroke.