Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study.

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer's disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer's disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer's disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10-19, 2.49 × 10-23, 1.35 × 10-67, and 4.81 × 10-9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10-8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer's disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer's disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.

The cost of Alzheimer's disease in China and re-estimation of costs worldwide.

INTRODUCTION: The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. METHODS: We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. RESULTS: The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. DISCUSSION: China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

Diagnosis and treatment of dementia in neurology outpatient departments of general hospitals in China.

INTRODUCTION: The status of dementia diagnosis and treatment of neurology outpatients in general hospitals in China remains unclear. METHODS: From neurology outpatients at 36 randomly selected hospitals, we first collected baseline data concerning the number of dementia doctors, memory clinics, and patients diagnosed with dementia. In stage 2, we intervened based on drawbacks discovered in stage 1, implementing a dementia initiative program. In stage 3, we reinvestigated the outpatients to determine the effects of intervention. RESULTS: After intervention, all 36 hospitals had established memory clinics (205 dementia doctors) compared with only 6 (47 dementia doctors) before intervention. The percentage of patients diagnosed with dementia significantly increased from 0.10% (536 dementia patients of 553,986 outpatients) in stage 1 to 0.41% (2482 dementia patients of 599,214 outpatients) in stage 3. DISCUSSION: Proper diagnosis and treatment are unavailable to many dementia patients because of a lack of dementia doctors and memory clinics in China.

Lipid metabolism and oxidative stress in patients with Alzheimer's disease and amnestic mild cognitive impairment.

Lipid metabolism and oxidative stress are key mechanisms in Alzheimer's disease (AD). The link between plasma lipid metabolites and oxidative stress in AD patients is poorly understood. This study was to identify markers that distinguish AD and amnestic mild cognitive impairment (aMCI) from NC, and to reveal potential links between lipid metabolites and oxidative stress. We performed non-targeted lipid metabolism analysis of plasma from patients with AD, aMCI, and NC using LC-MS/MS. The plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were assessed. We found significant differences in lipid metabolism between patients with AD and aMCI compared to those in NC. AD severity is associated with lipid metabolites, especially TG (18:0_16:0_18:0) + NH4, TG (18:0_16:0_16:0) + NH4, LPC(16:1e)-CH3, and PE (20:0_20:4)-H. SPH (d16:0) + H, SPH (d18:1) + H, and SPH (d18:0) + H were high-performance markers to distinguish AD and aMCI from NC. The AUC of three SPHs combined to predict AD was 0.990, with specificity and sensitivity as 0.949 and 1, respectively; the AUC of three SPHs combined to predict aMCI was 0.934, with specificity and sensitivity as 0.900, 0.981, respectively. Plasma MDA concentrations were higher in the AD group than in the NC group (p = 0.003), whereas plasma SOD levels were lower in the AD (p < 0.001) and aMCI (p = 0.045) groups than in NC, and GSH-Px activity were higher in the AD group than in the aMCI group (p = 0.007). In addition, lipid metabolites and oxidative stress are widely associated. In conclusion, this study distinguished serum lipid metabolism in AD, aMCI, and NC subjects, highlighting that the three SPHs can distinguish AD and aMCI from NC. Additionally, AD patients showed elevated oxidative stress, and there are complex interactions between lipid metabolites and oxidative stress.

A blood mRNA panel that differentiates Alzheimer's disease from other dementia types.

BACKGROUND: Messenger RNAs (mRNAs) have been reported to be associated with Alzheimer's disease (AD). In this study, we investigated whether plasma-based mRNAs could distinguish AD from cognitively normal controls and other types of dementia, including vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Plasma mRNA expression was measured in three independent datasets. Dataset 1 (n = 40; controls, 20; AD, 20) was used to identify the differentially expressed mRNAs. Dataset 2 (n = 122; controls: 60; AD: 62) was used to develop a diagnostic AD model using an mRNA panel. Furthermore, we applied the model to Dataset 3 (n = 334; control, 57; AD, 58; VaD, 55; PDD, 54; bvFTD, 55; DLB, 55) to verify its ability to identify AD and other types of dementia. RESULTS: Dataset 1 showed 22 upregulated and 21 downregulated mRNAs. A panel of six mRNAs distinguished AD from the control group in Dataset 2. The panel was used to successfully differentiate AD from other types of dementia in Dataset 3. CONCLUSIONS: An AD-specific panel of six mRNAs was created that can be used for AD diagnosis.

A Group of Long Non-coding RNAs in Blood Acts as a Specific Biomarker of Alzheimer's Disease.

Long non-coding RNAs (lncRNAs) have been identified to be involved in the pathogenesis of Alzheimer's disease (AD). In this study, we evaluated whether lncRNAs can be used to discriminate AD patients from controls and patients with other dementias, such as vascular, Parkinson's disease, behavioral variant frontotemporal, and dementia with Lewy body. In this study, we used three datasets to measure the blood lncRNA levels. A pilot study (dataset 1, n = 40; controls, 20; AD, 20) was used to screen for differentially expressed lncRNAs. Dataset 2 (n = 174; controls, 86; AD, 88) was used to identify a lncRNA panel for the diagnostic model. Dataset 3 (n = 333; control, 60; AD, 54; vascular dementia, 53; Parkinson's disease dementia, 55; behavioral variant frontotemporal dementia, 56; and dementia with Lewy body, 55) was used to validate the diagnostic model. In dataset 1, 12 upregulated and 15 downregulated lncRNAs were identified. In dataset 2, a panel of seven lncRNAs was found to have the ability to differentiate AD patients from controls. Finally, this panel was applied to dataset 3 to successfully distinguish AD from other dementias. This study proposes a panel of seven lncRNAs as specific and promising biomarker for AD diagnosis.

Executive function deficits and medial temporal lobe atrophy in late-life depression and Alzheimer's disease: a comparative study.

Objectives: Alzheimer's disease (AD) and late-life depression (LLD) frequently exhibit executive function deficits (EFD) and medial temporal lobe atrophy (MTA) as shared characteristics. The objective of this research was to examine the utility of the Trail Making Test (TMT) and the MTA scale in distinguishing between LLD and AD. Methods: A study of 100 patients, 50 with AD and 50 with LLD, was conducted using a cross-sectional design. The individuals were subjected to clinical evaluations to assess their level of depression and overall cognitive abilities, which included the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). We evaluated executive function deficits (EFD) through the use of the TMT, which includes both TMT-A and TMT-B. MTA was measured using magnetic resonance imaging. To evaluate the ability of TMT and MTA scale to distinguish between the two groups, a receiver operating characteristic (ROC) curve was utilized. To investigate the connections between MTA and neuropsychological measures, a correlation analysis was performed. Results: AD patients exhibited notably reduced MMSE, MoCA, and GDS scores, as well as an increased MTA total scores, time spent on TMT-A, and TMT-B compared to LLD patients (p < 0.05). TMT-A and TMT-B both exhibited excellent discriminatory power between AD and LLD, achieving area under curve (AUC) values of 92.2 and 94.2%, respectively. In AD patients, there was a negative correlation between MMSE and MoCA scores and MTA scores, while in LLD patients, there was a positive correlation between time spent on TMT-A and GDS scores and MTA scores. Conclusion: AD patients experience more severe EFD and MTA than LLD patients. The differential diagnosis of AD and LLD can be aided by the useful tool known as TMT. It is important to acknowledge that TMT is capable of capturing only a fraction of the executive function, thus necessitating a cautious interpretation of research findings.

Association studies of 19 candidate SNPs with sporadic Alzheimer's disease in the North Chinese Han population.

Genome-wide association studies (GWAS) identified multiple single-nucleotide polymorphisms (SNPs) that are associated with the pathogenesis of Alzheimer's disease (AD). As replication in independent studies remains the only way to validate proposed GWAS signals, we detect SNPs reported in the GWAS, in order to explore their association with sporadic AD (SAD) in the Chinese population. We analyzed genotype and allele distributions of 19 SNPs reported in GWAS in 191 SAD patients and 180 healthy controls. We found that higher frequencies of rs10868366 G and rs7019241 C carriers were observed in SAD patients compared with controls (rs10868366 G: P = 0.026, odds ratio (OR) = 1.4, 95% confidence intervals (CI) 1.0-1.9; rs7019241 C: P = 0.019, OR 1.4, 95% CI 1.6-1.9). Furthermore, rs10868366 G/T and rs7019241 C/T in GOLPH2 were in strong linkage disequilibrium and formed a relative protective factor rs10868366 T/rs7019241 T and a relative risk factor rs10868366 G/rs7019241 C. For SNP rs3826656 in near gene 5' region of CD33, the results revealed that in subjects with APOE ε4 alleles, the A allele was associated with a reduced risk of SAD compared with the G allele (OR 0.479; 95% CI 0.263-0.870, P = 0.015), and AA genotype was associated with a reduced risk of SAD compared with the genotype AG + GG (OR 0.395; 95% CI 0.158-0.659, P = 0.008). Our results support the view that rs10868366 and rs7019241 in GOLPH2 and rs3826656 in near gene 5' region of CD33 are significantly associated with SAD in the north Chinese Han population.

A circular RNA blood panel that differentiates Alzheimer's disease from other dementia types.

BACKGROUND: Circular RNAs (circRNAs) have been demonstrated to be associated with Alzheimer's disease (AD). Here, we conducted a study to explore whether circRNAs have the ability to differentiate AD from cognitively normal controls and other types of dementia, such as vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Three datasets were included in this study to measure blood circRNAs. The pilot study (Dataset 1, n = 40; controls, 20; AD, 20) was used to screen differentially expressed circRNAs. Dataset 2 (n = 124; controls, 61; AD, 63) was recruited for the establishment of the diagnostic model using a circRNA panel. Further, the Dataset 3 (n = 321; control, 58; AD, 60; VaD, 50; PDD, 51; bvFTD, 52; DLB, 50) was used to verify the diagnostic model. RESULTS: In Dataset 1, 22 upregulated and 19 downregulated circRNAs were revealed. In Dataset 2, a six-circRNA panel was found to be able to distinguish patients with AD from controls. Then this panel was applied to Dataset 3 and successfully differentiated AD from other types of dementia. CONCLUSION: This study suggested that a six-circRNA panel is AD-specific and a promising biomarker of AD.

Hyoid Elongation May Be a Rare Cause of Recurrent Ischemic Stroke in Youth-A Case Report and Literature Review.

The investigation for etiology of ischemic stroke in young adults remains a diagnostic challenge. Hyoid bone-related carotid injury is a rare and under-recognized cause of ischemic stroke, without established guidelines. We describe a case of recurrent ischemic stroke in a young patient presumably attributed to an impingement of the carotid artery by an elongated hyoid bone, and present other cases reported in the literature. Based on the imaging study as well as the lack of other findings, we attributed recurrent neurovascular events to the repetitive mechanical stimulation by the elongated hyoid bone that caused a vessel wall injury with subsequent thrombus and embolus. Given repeated recurrence under antiplatelet treatment, anticoagulation was added. The following 2-year follow-up showed no new neurologic events or any other complaints. Among the young, a broad spectrum of possibilities should be considered and we call attention to this infrequent etiology of ischemic stroke.

Preventing Ischemic Cerebrovascular Events in High-Risk Patients With Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning: A Single-Arm Study.

Background: Secondary stroke prevention after a high-risk, non-disabling ischemic cerebrovascular event needs to be enhanced. The study was conducted to investigate whether remote ischemic conditioning (RIC) is effective in preventing recurrent ischemic events within 3 months. Methods: This was a four-center, single-arm, open-label Phase IIa futility trial (PICNIC-One Study). Adult patients (≥18 years of age) who had an acute minor ischemic stroke (AMIS) with a National Institutes of Health Stroke Scale score ≤ 3 or a transient ischemic attack (TIA) with moderate-to-high risk of stroke recurrence (ABCD score ≥ 4) within 14 days of symptom onset were recruited. Patients received RIC as adjunctive therapy to routine secondary stroke prevention regimen. RIC consisted of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs (45 min) on bilateral upper limbs twice a day for 90 days. Results: A total of 285 patients met the study criteria, of which 167 provided signed informed consent and were enrolled. Data from 162 were analyzed with five subjects excluded. Recurrent AIS/TIA occurred in 6/162 (3.7%) patients within 3 months, with no occurrence of hemorrhagic stroke. The top three adverse events were upper limb pain (44/162, 27.2%), petechia (26/162, 16.0%), and heart palpitation (5/162, 3.1%). About 68 (42.0%) subjects completed ≥ 50% of 45-min RIC sessions. Conclusions: RIC is a safe add-on procedure and it has a potential benefit in reducing recurrent cerebrovascular events in patients with high-risk, non-disabling ischemic cerebrovascular events as the risk of stroke/TIA events is lower than expected; however, its compliance needs to be improved. Our study provides critical preliminary data to plan a large sample size, randomized controlled clinical study to systematically investigate the safety and efficacy of RIC in this population.

Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study.

BACKGROUND: China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). METHODS: For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. FINDINGS: Overall age-adjusted and sex-adjusted prevalence was estimated to be 6·0% (95% CI 5·8-6·3) for dementia, 3·9% (3·8-4·1) for Alzheimer's disease, 1·6% (1·5-1·7) for vascular dementia, and 0·5% (0·5-0·6) for other dementias. We estimated that 15·07 million (95% CI 14·53-15·62) people aged 60 years or older in China have dementia: 9·83 million (9·39-10·29) with Alzheimer's disease, 3·92 million (3·64-4·22) with vascular dementia, and 1·32 million (1·16-1·50) with other dementias. Overall MCI prevalence was estimated to be 15·5% (15·2-15·9), representing 38·77 million (37·95-39·62) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 2·69 [95% CI 2·43-2·98] to 6·60 [5·24-8·32]; MCI: from 1·89 [1·77-2·00] to 4·70 [3·77-5·87]); female sex (dementia: 1·43 [1·31-1·56]; MCI: 1·51 [1·43-1·59]); parental history of dementia (dementia: 7·20 [5·68-9·12]; MCI: 1·91 [1·48-2·46]); rural residence (dementia: 1·16 [1·06-1·27]; MCI: 1·45 [1·38-1·54]); fewer years of education (dementia: from 1·17 [1·06-1·29] to 1·55 [1·38-1·73]; MCI: from 1·48 [1·39-1·58] to 3·48 [3·25-3·73]); being widowed, divorced, or living alone (dementia: from 2·59 [2·30-2·90] to 2·66 [2·29-3·10]; MCI: from 1·58 [1·44-1·73] to 1·74 [1·56-1·95]); smoking (dementia: 1·85 [1·67-2·04]; MCI: 1·27 [1·19-1·36]), hypertension (dementia: 1·86 [1·70-2·03]; MCI: 1·62 [1·54-1·71] for MCI), hyperlipidaemia (dementia: 1·87 [1·71-2·05]; MCI: 1·29 [1·21-1·37]), diabetes (dementia: 2·14 [1·96-2·34]; MCI: 1·44 [1·35-1·53]), heart disease (dementia: 1·98 [1·73-2·26]; MCI: 1·17 [1·06-1·30]), and cerebrovascular disease (dementia: 5·44 [4·95-5·97]; MCI: 1·49 [1·36-1·62]). Nine of these risk factors are modifiable. INTERPRETATION: Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system. FUNDING: Key Project of the National Natural Science Foundation of China, National Key Scientific Instrument and Equipment Development Project, Mission Program of Beijing Municipal Administration of Hospitals, Beijing Scholars Program, Beijing Brain Initiative from Beijing Municipal Science & Technology Commission, Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine, and Beijing Municipal Commission of Health and Family Planning.

The efficacy of transcranial alternating current stimulation for treating post-stroke depression: Study Protocol Clinical Trial (SPIRIT Compliant).

BACKGROUND: The treatment of post-stroke depression (PSD) with anti-depressant drugs is partly practical. Transcranial alternating current stimulation (tACS) offers the potential for a novel treatment modality for adult patients with PSD. In this study, we will assess the efficacy and safety of tACS for treating PSD and explore its effect on gamma and beta-oscillations involving in emotional regulation. METHODS: The prospective study is an 8-week, double-blind, randomized, placebo-controlled trial. Seventy eligible participants with mild to moderate PSD aged between 18 years and 70 years will be recruited and randomly assigned to either active tACS intervention group or sham group. Daily 40-minute, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), and an additional 4-week observational period (week 8) will be followed up. The primary outcome is the proportion of participants having an improvement at week 8 according to the Hamilton Depression Rating Scale 17-Item (HAMD-17) score, including the proportion of participants having a decrease of ≥ 50% in HAMD-17 score or clinical recovery (HAMD-17 score ≤ 7). Secondary outcomes include neurological function, independence level, activities of daily living, disease severity, anxiety, and cognitive function. The exploratory outcomes are gamma and beta-oscillations assessed at baseline, week 4, and week 8. Data will be analyzed by logistical regression analyses and mixed-effects models. DISCUSSION: The study will be the first randomized controlled trial to evaluate the efficacy and safety of tACS at a 77.5-Hz frequency and 15-mA current in reducing depressive severity in patients with PSD. The results of the study will present a base for future studies on the tACS in PSD and its possible mechanism. TRIAL REGISTRATION NUMBER: NCT03903068, pre-results.

Cerebral arterial stiffness for predicting functional outcome in acute ischemic stroke.

To assess the association between cerebral arterial stiffness measured using the carotid-cerebral pulse wave velocity (ccPWV) and the functional outcome after acute ischemic stroke (AIS). We prospectively studied 336 consecutive patients (mean age, 60.58 ± 9.89 years; 73.81% male) with first-ever AIS who underwent examination by multimodal brain magnetic resonance, ccPWV, echocardiography, and carotid ultrasonography during the admission period. Ischemic stroke subtypes were classified using the Trial of Org 10172 in Acute Stroke Treatment classification system. A poor functional outcome was defined as a modified Rankin Scale score >2 at 3 months after stroke onset. We observed that 110 (32.74%) patients had a poor functional outcome. Multivariate logistic regression analysis revealed that ccPWV ≥ 6.66 m/s, calculated from the receiver operating characteristic (ROC) curve, was an independent predictor of a poor functional outcome [adjusted odds ratio, 6.27; 95% confidence interval (CI), 2.07-18.99]. ROC curve analysis showed that the area under the curve of ccPWV for predicting the 3-month functional outcome after AIS was 85.27% (95% CI, 80.95-89.58; P < 0.001). The optimal ccPWV cutoff point was 6.66 m/s, with a sensitivity of 82.73% and specificity of 77.88%. Furthermore, the addition of ccPWV to the predictive model significantly improved the discrimination ability for a poor functional outcome. Cerebral arterial stiffness, measured using the ccPWV on admission, has value as an independent prognostic factor for predicting the long-term functional outcome in patients with AIS.

Efficacy and safety of the compound Chinese medicine SaiLuoTong in vascular dementia: A randomized clinical trial.

INTRODUCTION: No licensed medications are available to treat vascular dementia (VaD). METHODS: Patients were randomly assigned to experimental groups (SaiLuoTong [SLT] 360 or 240 mg for groups A and B for 52 weeks, respectively) or placebo group (SLT 360 mg and 240 mg for group C only from weeks 27 to 52, respectively). RESULTS: Three hundred twenty-five patients were included in final analysis. At week 26, the difference in VaD Assessment Scale-cognitive subscale scores was 2.67 (95% confidence interval, 1.54 to 3.81) for groups A versus C, and 2.48 (1.34 to 3.62) for groups B versus C (both P < .0001). However, at week 52, no difference was observed among the groups on the VaD Assessment Scale-cognitive subscale (P = .062) because of the emerging efficacy of SLT in placebo beginning at week 27. DISCUSSION: This study suggests that SLT is effective for treatment of VaD, and this compound Chinese medicine may represent a better choice to treat VaD.

Overlap between Headache, Depression, and Anxiety in General Neurological Clinics: A Cross-sectional Study.

BACKGROUND: Many studies have reported that depression and anxiety have bidirectional relationship with headache. However, few researches investigated the roles of depression or anxiety in patients with headache. We surveyed the prevalence of depression and anxiety as a complication or cause of headache among outpatients with a chief complaint of headache at neurology clinics in general hospitals. Additional risk factors for depression and anxiety were also analyzed. METHODS: A cross-sectional study was conducted at 11 general neurological clinics. All consecutive patients with a chief complaint of headache were enrolled. Diagnoses of depression and anxiety were made using the Chinese version of the Mini International Neuropsychiatric Interview, and those for headache were made according to the International Classification of Headache Disorders, 2nd Edition. The headache impact test and an 11-point verbal rating scale were applied to assess headache severity and intensity. Logistic regression was used to analyze risk factors of patients with headache for depression or anxiety. RESULTS: A total of 749 outpatients with headache were included. Among them, 148 (19.7%) were diagnosed with depression and 103 (13.7%) with anxiety. Further analysis showed that 114 (15.2%) patients complaining headache due to somatic symptoms of psychiatric disorders and 82 (10.9%) had a depression or anxiety comorbidity with headache. Most patients with depression or anxiety manifested mild to moderate headaches. Poor sleep and severe headache-related disabilities were predictors for either depression or anxiety. CONCLUSION: Clinicians must identify the etiology of headache and recognize the effects of depression or anxiety on headache to develop specific treatments.

Prognostic value of copeptin in patients with acute stroke.

CONTEXT: There is a need to improve stroke care through the prompt identification of stroke patients at increased risk of an adverse outcome. OBJECTIVE: To evaluate the prognostic value of copeptin in patients with stroke. METHODS: We systematically searched PubMed and Embase for relevant studies. Poor outcome and mortality were analyzed. RESULTS: Twelve studies, containing 2682 patients, were included. Pooled analysis showed that copeptin is an independent prognostic marker of poor outcome after acute stroke and there is a borderline effect of copeptin in predicting mortality after acute stroke. CONCLUSIONS: Copeptin is an independent predictor of poor outcome and mortality for patients with acute stroke.

(R)-3-oxobutyl 3-hydroxybutanoate (OBHB) induces hyperketonemiain Alzheimer's disease.

The present study demonstrates the effect of (R)-3-oxobutyl 3-hydroxybutanoate (OBHB) on hyperketonemia in 2 patients with Alzheimer's disease dementia who were performed a mini-mental state examination score of above 11 and 10. The patients were treated with OBHB for 24 months and received usual diet. The patients were administered 15 g of OBHB three times per day for two days. The dosage of OBHB was increased to 30 g three times daily from the day 4. OBHB was always taken after adding with soda-flavoured syrups in order to mask the bitter taste. The measurement of plasma ß-hydroxybutyrate (ßHB) levels after every week was performed to determine OBHB plasma ßHB dose-response relationships. Precision Xtra Glucose and Ketone Monitoring System (Abbott Diabetes Care, Inc., Alameda, CA, USA) was used to measure ßHB levels in the blood samples. We did not observe any adverse effects of OBHB in any of the patients and it was well tolerated throughout the 24 months treatment period. Both of the patients showed marked improvement in mood, behaviour, self-care, cognitive and daily activity performance. The results revealed a marked improvement in conversation and interaction after administration of OBHB doses. The biochemical investigation of the blood samples before, during OBHB treatment and after 24 months of the treatment revealed only minor changes in the plasma lipids. There was a decrease in cholesterol level from 251 to 158 and 247 to 152 mg/dL in the two patients respectively after 24 months of the treatment. Similarly the level of high-density lipoprotein cholesterol was found to decrease from 157 to 79 and 149 to 76 mg/dL, respectively in two patients. Thus OBHB can be a promising agent in the treatment of hyperketonemia and can be taken as an oral supplement without changing the habitual diet.

Intravenous versus intra-arterial thrombolysis in ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Reperfusion following ischemic stroke can be attained by either intravenous thrombolysis (IVT) or intra-arterial thrombolysis (IAT). Only a limited number of randomized prospective studies have compared the efficacy and safety of IVT and IAT. This meta-analysis investigated possible clinical benefits of IAT relative to IVT in patients with acute ischemic stroke. METHODS: We searched the PubMed, Cochrane, and Google Scholar databases through October 2013 for manuscripts that describe the findings of randomized controlled or prospective studies that evaluated the outcomes of patients with ischemic stroke who were treated with IVT or IAT. The clinical outcome measures were score on the modified Rankin scale (mRS) and mortality at 90 days. A favorable outcome was defined as an mRS score of 0 to 2. RESULTS: For the mRS, the combined odds ratio (OR) of 3.28 (95% confidence interval (CI), 1.91 to 5.65, P < 0.001) indicated that patients who received IAT had a significantly higher chance for a favorable outcome than did those who received IVT. For mortality, the OR indicated that IAT therapy significantly reduced the proportion of patients who died within 90 days of the procedure (combined OR, 0.40; 95%CI, 0.17 to 0.92; P = 0.032). CONCLUSION: This meta-analysis determined that IAT conferred a significantly greater probability of achieving a favorable outcome compared with IVT. There was also a significant difference in mortality rates between IAT and IVT. The studies included in this analysis were small and heterogeneous; therefore, larger randomized prospective clinical studies are necessary to further investigate this issue.

Differential acetylcholine and choline concentrations in the cerebrospinal fluid of patients with Alzheimer's disease and vascular dementia.

BACKGROUND: An important aspect of Alzheimer's disease (AD) is loss or impairment of cholinergic neurons. It is controversial whether there is a similar cholinergic impairment and cerebral deficit of acetylcholine (ACh) in the case of vascular dementia (VD). The purpose of this study was to explore the levels of ACh and choline (Ch) in the cerebrospinal fluid (CSF) of patients with AD and VD, and their possible relationship with cognitive impairment. METHODS: Twenty-two AD patients, twenty-two VD patients, and twenty normal controls were recruited and scored with a Mini-Mental State Examination (MMSE). CSF concentrations of ACh and Ch were measured using high-performance liquid chromatography with an electrochemical detector (HPLC-ECD) and the results were then compared to cognitive status. RESULTS: ACh concentrations in CSF of AD patients [(10.7 +/- 5.1) nmol/L] and VD patients [(16.8 +/- 7.4) nmol/L] were both significantly lower than in controls [(34.5 +/- 9.0) nmol/L, t = 10.67, P < 0.001; t = 6.91, P < 0.001]. Both results correlated positively with MMSE scores (rs = 0.88 and rs = 0.85, respectively, P < 0.01). The CSF concentration of Ch was significantly higher in VD patients [(887.4 +/- 187.4) nmol/L] compared to AD patients [(627.6 +/- 145.1) nmol/L, t = 6.4, P < 0.001] and controls [(716.0 +/- 159.4) nmol/L, t = 4.2, P = 0.002]. CSF Ch concentration showed no difference between AD patients and normal controls, nor did it correlate with MMSE score in any of the three groups. CONCLUSIONS: The positive correlation between ACh deficit and cognitive impairment suggests that ACh is an important neurotransmitter for memory. The similar decrease in ACh concentration in AD and VD patients may imply a similar pathogenesis for the process of cognitive impairment involved in these two disorders. The elevated CSF levels of Ch in VD patients compared to AD patients may be useful diagnostically. Cholinesterase inhibitors may be helpful not only for AD patients, but also for VD patients.