Edaravone dexborneol promotes M2 microglia polarization against lipopolysaccharide-induced inflammation via suppressing TLR4/MyD88/NF-κB pathway.

Edaravone dexborneol (ED) is a novel neuroprotective compound that consists of two active ingredients, edaravone and ( +)-borneol in a 4:1 ratio, which has been shown the anti-inflammatory properties in animal models of ischemic stroke, cerebral hemorrhage, and autoimmune encephalomyelitis. However, the effect of ED on the polarization of microglia in neuroinflammation has not been elucidated. This study was to investigate the effects of ED on the polarization of microglia induced by lipopolysaccharide (LPS) and potential mechanisms. BV-2 microglial cells were incubated with ED (100, 200, and 400 µM) for 2 h, followed by lipopolysaccharide (LPS, 1 µg/ml) for 12 h. The researchers used the Griess method, western blot, immunocytochemistry, and subcellular fractionation to assess the effects and potential mechanisms of ED on neuroinflammatory reactions. The expression of ROS and the activities of antioxidant enzymes (SOD, GPx, and CAT) in LPS-induced BV-2 cells were also measured using the DCFH-DA fluorescent probe and colorimetric methods, respectively. It was observed that ED significantly declined the levels of TLR4/NF-κB pathway-associated proteins (TLR4, MyD88, p65, p-p65, IκBα, p-IκBα, IKKß, p-IKKß) and therefore inhibited LPS-induced production of NO, IL-1ß, and TNF-α. Moreover, ED markedly downregulated the M1 marker (iNOS) and upregulated the M2 marker (Arginase-1, Ym-1). In addition, ED also reduced ROS generation and enhanced GPx activity. ED induced the polarization of LPS-stimulated microglia from M1 to M2 against inflammation by negatively regulating the TLR4/MyD88/NF-κB signaling pathway. Additionally, ED performed antioxidative function by depleting the intracellular excessive ROS caused by LPS through the enhancement of the enzymatic activity of GPx. ED may be a potential agent to attenuate neuroinflammation via regulating the polarization of microglia.

Predictors of good outcomes and mortality after thrombectomy for basilar artery occlusion within 12 hours of onset.

BACKGROUND: Patients with acute basilar artery occlusion (ABAO) who undergo combined standard medical treatment (SMT) and endovascular thrombectomy (EVT) may still have unsatisfactory outcomes. This study was conducted to identify the factors that may impact their outcomes. METHODS: We retrospectively reviewed the data of all patients with ABAO combined with SMT and EVT in the endovascular treatment for acute basilar artery occlusion (ATTENTION) trial. A good outcome is defined as a modified Rankin Scale (mRS) score of 0-3, a poor outcome as mRS score of 4-6, and mortality as death at 90-day follow-up. The study analyzed various factors influencing the patients' good outcomes and mortality. RESULTS: The study included 221 patients (148 men and 73 women). Among these patients, 45.7% achieved an mRS score of 0-3, while the overall mortality rate was 37.1% (82/221). A good outcome was significantly associated with younger age (adjusted OR 0.96; 95% CI 0.93 to 0.99; P=0.019), a baseline posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) of 8-10 (adjusted OR 2.34; 95% CI 1.07 to 5.12; P=0.034), and post-procedure pc-ASPECTS of 8-10 (adjusted OR 1.40; 95% CI 1.07 to 1.84; P=0.013). Additionally, time from puncture to reperfusion (adjusted OR 2.02; 95% CI 1.2 to 3.41; P=0.008) and intracranial hemorrhage (adjusted OR 3.59; 95% CI 1.09 to 11.8; P=0.035) were associated with 90-day mortality. CONCLUSIONS: Younger age, baseline pc-ASPECTS of 8-10, and higher post-procedure pc-ASPECTS could effectively predict good outcomes for patients with ABAO undergoing EVT. Additionally, a prolonged time from puncture to reperfusion and intracranial hemorrhage can independently predict mortality. TRIAL REGISTRATION NUMBER: NCT04751708.

The Role of Hyperdense Basilar Artery Sign in Predicting Outcome of Acute Basilar Artery Occlusion within Twelve Hours of Onset.

BACKGROUND: The correlation between hyperdense basilar artery sign (HDBAS) and outcome after acute basilar artery occlusion (ABAO) is debated. Our objective was to determine the usefulness of HDBAS in predicting the outcomes of patients with ABAO after endovascular treatment (EVT), intravenous thrombolysis (IVT), and best medical treatment (BMT). METHODS: The study participants were selected from the ATTENTION trial. The primary outcome of the study was a 90-day modified Rankin Scale (mRS) score, and the secondary outcome was the recanalization rate, any intracranial hemorrhage, and 90-day mortality. RESULTS: The study comprised 276 participants, with cohorts for EVT (n = 188), IVT (n = 82), and BMT (n = 88). In the EVT cohort, HDBAS was not associated with 90-day mRS score (adjusted odds ratio [OR], 0.87; 95% confidence interval [CI], 0.51-1.48; P = 0.6029), the recanalization after 24 hours of onset (adjusted OR, 0.76; 95% CI, 0.30-3.61; P = 0.9422), and 90-day mortality (adjusted OR, 0.77; 95% CI, 0.41-1.46; P = 0.4238). In the IVT cohort, HDBAS was not associated with a 90-day mRS score (adjusted OR, 0.69; 95% CI, 0.31-1.56; P = 0.3742), the recanalization after 24 hours of onset (adjusted OR, 2.24; 95% CI, 0.47-10.78; P = 0.3132), and 90-day mortality (adjusted OR, 0.64; 95% CI, 0.26-1.57; P = 0.3264). Similarly, in the BMT cohort, HDBAS was not associated with 90-day mRS score (adjusted OR, 1.11; 95% CI, 0.47-2.63; P = 0.8152), the recanalization after 24 hours of onset (adjusted OR, 1.27; 95% CI, 0.40-4.02; P = 0.6874), and 90-day mortality (adjusted OR, 1.17; 95% CI, 0.46-2.96; P = 0.748). CONCLUSIONS: HDBAS may not be a reliable predictor of outcomes for patients with ABAO, regardless of whether they received EVT, IVT, or BMT.

ADVISING score: a reliable grading scale based on injury and response for intracerebral haemorrhage.

BACKGROUND: Intracerebral haemorrhage (ICH) is the most devastating form of stroke causing high morbidity and mortality. We aimed to develop a novel clinical score incorporating multisystem markers to predict functional dependence at 90 days after ICH. METHODS: We analysed data from Chinese Cerebral Hemorrhage: Mechanism and Intervention study. Multivariable logistic regression analysis was used to identify the factors associated with 90-day functional dependency (the modified Rankin Scale ≥3) after ICH and develop the ADVISING scoring system. To test the scoring system, a total of 2111 patients from Hubei province were included as the training cohort, and 733 patients from other three provinces in China were included as an external validation cohort. RESULTS: We found nine variables to be significantly associated with functional dependency and included in the ADVISING score system: age, deep location of haematoma, volume of haematoma, National Institutes of Health Stroke Scale, aspartate transaminase, international normalised ratio, neutrophil-lymphocyte ratio, fasting blood glucose and glomerular filtration rate. Individuals were divided into 12 different categories by using these nine potential predictors. The proportion of patients who were functionally dependent increased with higher ADVISING scores, which showed good discrimination and calibration in both the training cohort (C-statistic, 0.866; p value of Hosmer-Lemeshow test, 0.195) and validation cohort (C-statistic, 0.884; p value of Hosmer-Lemeshow test, 0.853). The ADVISING score also showed better discriminative performance compared with the other five existing ICH scores (p<0.001). CONCLUSIONS: ADVISING score is a reliable tool to predict functional dependency at 90 days after ICH.

Prediction of Neurological Deterioration After Intracerebral Hemorrhage: The SIGNALS Score.

Background Intracerebral hemorrhage is the most disabling and lethal form of stroke. We aimed to develop a novel clinical score for neurological deterioration during hospitalization after intracerebral hemorrhage. Methods and Results We analyzed data from the CHERRY (Chinese Cerebral Hemorrhage: Mechanism and Intervention) study. Two-thirds of eligible patients were randomly allocated into the training cohort (n=1027) and one-third into the validation cohort (n=515). Multivariable logistic regression was used to identify factors associated with neurological deterioration (an increase in National Institutes of Health Stroke Scale of ≥4 or death) within 15 days after symptom onset. A prediction score was developed based on regression coefficients derived from the logistic model. The site, size, gender, National Institutes of Health Stroke Scale, age, leukocyte, sugar (SIGNALS) score was developed as a sum of individual points (0-8) based on site (1 point for infratentorial location), size (3 points for >20 mL of supratentorial hematoma volume or 2 points for >10 mL of infratentorial hematoma volume), sex (1 point for male sex), National Institutes of Health Stroke Scale score (1 point for >10), age (1 point for ≥70 years), white blood cell (1 point for>9.0×109/L), and fasting blood glucose (1 point>7.0 mmol/L). The proportion of patients who suffered from neurological deterioration increased with higher SIGNALS score, showing good discrimination and good calibration in the training cohort (C statistic, 0.821; Hosmer-Lemeshow test, P=0.687) and in the validation cohort (C statistic, 0.848; Hosmer-Lemeshow test, P=0.592), respectively. Conclusions The SIGNALS score reliably predicts the risk of in-hospital neurological deterioration of patients with intracerebral hemorrhage.

Clinical and Prognostic Characteristics of Recurrent Intracerebral Hemorrhage: A Contrast to First-Ever ICH.

This study aimed to compare clinical and prognostic characteristics between recurrent and first-ever ICH. Four thousand twelve patients entered the study, and 64% of them were male. The median age is 62 years (interquartile range, 55-71). Among them, 3,750 (93.5%) patients had no experience of previous ICH, and 262 (6.5%) patients were considered as recurrent ICH. We compared demographic data, baseline clinical characteristics, imaging information, hematological parameters, and clinical outcomes between recurrent and first-ever ICH. We found that recurrent ICH was significantly associated with older age, more frequent history of ischemic heart disease, ischemic stroke, hypertension, and hyperlipidemia, while patients with recurrent ICH had previously received more antihypertensive therapy, and showed lower admission blood pressure (median, 160 vs. 167 mmHg) and higher baseline of National Institute of Health stroke scale (NIHSS) score (median, 10 vs. 9). We also demonstrated that recurrent ICH was an independent risk factor of 3-month function dependence after adjusting for many potentially competitive risk factors.

The evaluation of sleep disturbances for Chinese frontline medical workers under the outbreak of COVID-19.

OBJECTIVE: To evaluate sleep disturbances of Chinese frontline medical workers (FMW) under the outbreak of coronavirus disease 2019 (COVID-19), and make a comparison with non-FMW. METHODS: The medical workers from multiple hospitals in Hubei Province, China, volunteered to participate in this cross-sectional study. An online questionnaire, including Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS) and Visual Analogue Scale (VAS), was used to evaluate sleep disturbances and mental status. Sleep disturbances were defined as PSQI>6 points or/and AIS>6 points. We compared the scores of PSQI, AIS, anxiety and depression VAS, as well as prevalence of sleep disturbances between FMW and non-FMW. RESULTS: A total of 1306 subjects (801 FMW and 505 non-FMW) were enrolled. Compared to non-FMW, FMW had significantly higher scores of PSQI (9.3 ± 3.8 vs 7.5 ± 3.7; P < 0.001; Cohen's d = 0.47), AIS (6.9 ± 4.3 vs 5.3 ± 3.8; P < 0.001; Cohen's d = 0.38), anxiety (4.9 ± 2.7 vs 4.3 ± 2.6; P < 0.001; Cohen's d = 0.22) and depression (4.1 ± 2.5 vs 3.6 ± 2.4; P = 0.001; Cohen's d = 0.21), as well as higher prevalence of sleep disturbances according to PSQI > 6 points (78.4% vs 61.0%; relative risk [RR] = 1.29; P < 0.001) and AIS > 6 points (51.7% vs 35.6%; RR = 1.45; P < 0.001). CONCLUSION: FMW have higher prevalence of sleep disturbances and worse sleep quality than non-FMW. Further interventions should be administrated for FMW, aiming to maintain their healthy condition and guarantee their professional performance in the battle against COVID-19.

A Mouse Model of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Induced Parkinson Disease Shows that 2-Aminoquinoline Targets JNK Phosphorylation.

BACKGROUND The pathological features of Parkinson disease (PD) include motor deficits, glial cell activation, and neuroinflammation. The neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has an oxidation product, 1-methyl-4-phenylpyridinium ion (MPP+). This study aimed to investigate the effects of 2-aminoquinoline on motor deficits in a mouse model of MPTP-induced PD and cultured mouse astrocytes treated with MPP+, to determine the effects on astrocyte proliferation and apoptosis. MATERIAL AND METHODS Motor deficits in the mouse model of MPTP-induced PD were investigated using the climbing time, suspension time, and swim time tests. Cultured mouse astrocytes were treated with MPP+, and mice with MPTP-induced PD were treated with increasing doses of 2-aminoquinoline. The MTT assay was used to measure astrocyte viability. Astrocyte apoptosis was assessed by confocal fluorescence microscopy using Annexin­V and fluorescein isothiocyanate (FITC) staining. Western blot measured the levels of Bax, p­JNK, Bcl­2, and caspase­3. RESULTS In the mouse model of MPTP-induced PD, motor deficit tests showed that 2-aminoquinoline reduced the impaired motor function during the climbing time, the suspension time, and the swim time tests in a dose-dependent manner. Pre-treatment with 2-aminoquinoline significantly reduced the proliferation and apoptosis of astrocytes induced by MPP+ in vitro, in a dose-dependent manner (P<0.05). The levels of p­JNK and cleaved caspase­3 levels were significantly reduced in astrocytes treated with MPP+ following pre-treatment with 2-aminoquinoline, which also reversed the increase in the Bax/Bcl­2 ratio. CONCLUSIONS In the mouse model of MPTP-induced PD, 2-aminoquinoline reduced motor deficiencies, inhibited MPP+ activated astrocyte apoptosis, and regulated the Bax/Bcl-2 ratio by targeting p-JNK.

Association of the Polymorphisms and Plasma Level of CHI3L1 with Alzheimer's Disease in the Chinese Han Population: A Case-Control Study.

OBJECTIVE: To investigate whether the polymorphisms and plasma level of chitinase-3-like protein 1 (CHI3L1) are associated with Alzheimer's disease (AD) in the Chinese Han population. METHODS: A total of 166 patients who were initially diagnosed with AD were enrolled as the case group, and 184 healthy subjects were recruited as the healthy controls. TaqMan® SNP genotyping assays were applied for the genotyping of rs4950928, rs10399931 and rs6691378. The plasma level of CHI3L1 was determined by enzyme-linked immunosorbent assay. RESULTS: The CG+GG genotype of rs4950928 C>G is a protective factor for AD and could effectively reduce the severity of AD. Patients with the CT+TT genotype of rs10399931 C>T had a significantly increased risk of AD, and it apparently aggravated the severity of AD. Moreover, the plasma CHI3L1 level in AD patients was significantly higher than that in healthy controls, which was increased with the severity of AD. A Kaplan-Meier survival curve showed that significant differences in 5-year survival rates were found in AD patients in different genotypes of CHI3L1 rs4950928 C>G and rs10399931 C>T. The AD patients and healthy controls who carried the CG+GG genotype of rs4950928 C>G had lower plasma CHI3L1 levels than CC genotype carriers. However, the CT+TT genotype of rs10399931 in the AD patients had an elevated plasma level of CHI3L1 as compared with the CC genotype. Binary logistic regression analysis showed that the plasma level of CHI3L1, the CC genotype of rs4950928 C>G and the CT+TT genotype of rs10399931 C>T were risk factors for AD. CONCLUSION: Polymorphisms of the CHI3L1 gene (rs4950928 C>G and rs10399931 C>T) are associated with the risk and prognosis of AD and can affect the expression of CHI3L1 in plasma.

Guillain-Barré syndrome in southern China: retrospective analysis of hospitalised patients from 14 provinces in the area south of the Huaihe River.

OBJECTIVES: The clinical and epidemiological profiles of Guillain-Barré syndrome (GBS) in southern China have yet to be fully recognised. We aimed to investigate the subtypes of GBS in southern China, compare the clinical features of demyelinating form with that of axonal form and test whether preceding infections and age have influence on the clinical phenotype, disease course and severity of GBS. METHODS: Medical records of patients with a diagnosis of GBS admitted to 31 tertiary hospitals, located in 14 provinces in southern China, from 1 January 2013 to 30 September 2016, were collected and retrospectively reviewed. RESULTS: Finally. 1056 patients, including 887 classic GBS and 169 variants, were enrolled. The 661 classic patients with available electromyographic data were grouped as having acute inflammatory demyelinating polyneuropathy (AIDP, 49.0%), acute motor axonal neuropathy (AMAN, 18.8%), inexcitable (0.9%) and equivocal (31.3%). In contrast to AIDP, patients with AMAN were characterised by earlier nadir (P=0.000), higher Hughes score at nadir (P=0.003) and at discharge (P=0.000). Preceding upper respiratory infections were identified in 369 (34.9%) patients, who were more inclined to develop AIDP (P=0.000) and Miller-Fisher syndrome (P=0.027), whereas gastrointestinal infection were found in 89 (8.4%) patients, who were more prone to develop AMAN (P=0.000), with more severe illness (P=0.001) and longer hospital stay (P=0.009). Children (≤15 years) and the elderly (≥56 years) were more severe at nadir, the elderly had the longest hospital stay (P=0.023). CONCLUSION: AIDP is the predominant form in southern China, which is different from data of northern China. The different subtypes, preceding infection and age of onset can partially determine the disease progression, severity and short-term recovery speed of GBS. CLINICAL TRIAL REGISTRATION: ChiCTR-RRC-17014152.

Changes of cerebrospinal fluid Aß42, t-tau, and p-tau in Parkinson's disease patients with cognitive impairment relative to those with normal cognition: a meta-analysis.

The cerebrospinal fluid (CSF) signature of reduced amyloid beta 1-42 (Aß42), elevated total tau (t-tau), and phosphorylated tau181 (p-tau) is important for the early diagnosis of Alzheimer's disease (AD). Aß42, t-tau, and p-tau have been reported in numerous studies to contribute to predicting cognitive impairment in Parkinson's disease (PDCI). However, no consistent conclusion can be drawn so far. Literatures regarding Aß42, t-tau, and p-tau in CSF were systematically reviewed, and a meta-analysis was thus performed to evaluate the changes of these biomarkers in PDCI patients, including PD with mild cognitive impairment (PDMCI) and PD dementia (PDD) patients, relative to PD with normal cognition (PDNC) patients. Databases of "PubMed," "EBSCO," and "Springer" were retrieved for articles concerning Aß42, t-tau, and p-tau in PDCI patients relative to those in PDNC patients published from January 1, 2000 to February 1, 2017. The following keywords were set, namely, "dementia" or "cognitive impairment" or "mild cognitive impairment" and "cerebrospinal fluid" and "Parkinson*." Sixteen articles comprising 590 PDCI patients and 1182 PDNC patients were included. The results showed that CSF Aß42 level in PDCI cohort was lower than that in PDNC cohort (pooled Std.MD = -0.44, 95% CI [-0.61, -0.26], p < 0.00001). Reduced Aß42 (pooled Std.MD = -0.60, 95% CI [-0.75, -0.45], p < 0.00001) as well as elevated t-tau (pooled Std.MD = 0.21, 95% CI [0.06, 0.35], p = 0.006) and p-tau (pooled Std.MD = 0.36, 95% CI [0.02, 0.69], p = 0.04) could be observed in PDD cohort compared with PDNC cohort. Therefore, amyloid pathology and tauopathy may participate in the development of PDD, which is similar to AD.

A meta-analysis of cerebrospinal fluid visinin-like protein-1 in alzheimers disease patients relative to healthy controls and mild cognitive impairment patients.

OBJECTIVE: To compare cerebrospinal fluid visinin-like protein-1 (CSF VLP-1) in alzheimer`s disease (AD) with that in healthy controls and mild cognitive impairment (MCI) patients and find out possible sources of heterogeneity. METHODS: "Visinin-like protein-1" and "alzheimer`s disease" were employed to search "PubMed", "Springer" and "Medline" databases until July 2016 and standard mean difference (Std.MD) was calculated. Besides, subgroup analysis and meta-regression were performed to explore the possible heterogeneity sources. RESULTS: Seven studies involved 1151 participants were pooled. The CSF VLP-1 in AD patients was higher than that in healthy controls and MCI patients (pooled Std.MD=0.81, 95% CI: [0.47, 1.16], p<0.00001). As shown by subgroup analysis, population variations were one of heterogeneity sources. Meta-regression revealed that Hedges`s g of CSF VLP-1 was correlated with Std.MD of t-tau (r=0.560, p=0.006) and amyloid beta42 (r=-0.386, p=0.013). CONCLUSION: The CSF VLP-1 in AD patients is higher than that in healthy controls and MCI patients. The changes of VLP-1 in AD patients relative to healthy controls and MCI patients is less pronounced than that of core biomarkers, such as amyloid beta42, t-tau and p-tau. Population variations, increasing t-tau and decreasing amyloid beta42 in AD patients relative to healthy controls and MCI patients were the main sources of heterogeneity.

Cerebrospinal fluid levels of neurofilament light chain in multiple system atrophy relative to Parkinson's disease: a meta-analysis.

As a biomarker of axonal injury, neurofilament light chain (NFL) in multiple system atrophy (MSA) patients and Parkinson's disease (PD) patients has been investigated by numerous studies. However, cerebrospinal fluid (CSF) NFL changes are conflicting in MSA patients relative to PD patients to date. Therefore, the current study was carried out to find out possible heterogeneity sources. Furthermore, "Neurofilament", "Neurofilament light chain" and "Multiple system atrophy" were employed to search "PubMed", "Springer" and "Medline" databases until August 2016 with standard mean difference (Std.MD) being calculated. In addition, subgroup analysis and meta-regression were performed to assess possible heterogeneity sources. Nine studies were pooled, in which 212 MSA patients and 373 PD patients were involved. Moreover, CSF NFL in MSA patients was higher than that in PD patients [pooled Std.MD = 1.56, 95% CI (1.12, 2.00), p < 0.00001] with significant heterogeneity (I 2 = 76%). Besides, population variations, sample size, the difference in CSF phosphorylated tau (p-tau) levels between MSA patients and PD patients, and Hoehn-Yahr staging of PD patients were the main heterogeneity sources. As shown by meta-regression, Hedges's g of CSF NFL was correlated with CSF Std.MD of α-synuclein between MSA patients and healthy controls (r = -1.34824, p = 0.00025). Therefore, CSF NFL increased in MSA patients relative to PD patients. Meta-regression showed that NFL was associated with α-synuclein in CSF of MSA patients relative to healthy controls. Due to the influence of heterogeneity sources, more prospective large sample studies are still needed to assess CSF NFL changes in MSA patients relative to PD patients.

Circulating insulin-like growth factor 1 and insulin-like growth factor binding protein-3 level in Alzheimer's disease: a meta-analysis.

It has been reported that the associations between circulating insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) and Alzheimer's disease (AD) are controversial. Thus, present meta-analysis was carried out to confirm the probable associations. We searched "PubMed", "Springer" and "Medline" databases using the term ("insulin-like growth factor-1" or "IGF-1" or "insulin-like growth factor binding protein-3" or "IGFBP-3") and ("Alzheimer's disease") until April 2016. Furthermore, standard mean differences (SMDs) were calculated. A total of seven reports involving 1342 percipients were pooled. SMDs were -0.25 (P = 0.22) and -0.33 (P = 0.08) for IGF-1 and IGFBP-3, respectively. Furthermore, the circulating IGF-1 levels in AD patients were lower than controls when studies with the difference of mean age ≤1 year (SMD -0.57, P = 0.007) or 2 years (SMD -0.58, P = 0.02) or difference of mean MMSE scores ≤10 scores (SMD -0.94, P < 0.00001), or studies from Europe (SMD -0.89, P < 0.00001) were excluded. In addition, the circulating IGFBP-3 levels in AD patients were lower than controls when studies with the difference of mean age ≤2 years (SMD -0.62, P = 0.006) or difference of mean MMSE scores ≤6 scores (SMD -0.48, P = 0.0004), 7 scores (SMD -0.58, P = 0.02), or 8 scores (SMD -0.80, P = 0.03) were excluded. Even though no significant difference of circulating IGF-1 and IGFBP-3 levels in AD patients comparing with controls was found in present meta-analysis, the current study provided the evidence that the circulating IGF-1 and IGFBP-3 level in AD patients were influenced by the difference of mean age as well as MMSE scores. Furthermore, circulating IGFBP-3 levels in AD patients may be decreased earlier than IGF-1.