Long-term effect of extreme temperature on cognitive function of middle-aged and older adults in China.

BACKGROUND: Several studies have explored the association between temperature and cognitive function. However, few studies have examined the effect of extreme temperature on cognitive function. In this study, we aimed to quantify the long-term effect of extreme temperature (e.g., heat waves, cold spells, and hot night excess (HNE)) on cognitive performance in middle-aged and older people in China. METHOD: We investigated 7915 aged >45 years people from the China Health and Retirement Longitudinal Study (CHARLS), surveyed in 2011 and 2015. A structured questionnaire was utilized to assess cognitive function, including four dimensions: episodic memory, attention, orientation, and visuo-construction. Hourly ambient temperature from the ERA5-Land datasets were used to calculate variables indicating extreme temperature. We performed difference-in-difference (DID) models to assess the potential causal relationship between extreme temperature and cognitive function. RESULTS: Non-linear analyses suggested that both sustained increases in temperature and excessive variability in temperature increased the risk of cognitive decline. Meanwhile, we observed the extra risk of global cognitive function decline was 2.3% (95% Confidence interval (95% CI): 0.2%, 4.4%) for heat waves (one unit increase) and 5.9% (95% CI: 0.6%, 11.6%) for HNE (one unit increase), while the association for cold spells was insignificant. Two cognitive dimensions, episodic memory and visuo-construction, were sensitive to these two heat-related factors. CONCLUSION: Extreme temperature was inversely related to cognitive performance in middle-aged and older adults, which was substantial for heat waves and HNE particularly. The effect size varied by cognitive dimensions.

Coronavirus disease 2019 is threatening stroke care systems: a real-world study.

BACKGROUND: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the stroke care systems have been seriously affected because of social restrictions and other reasons. As the pandemic continues to spread globally, it is of great significance to understand how COVID-19 affects the stroke care systems in mainland China. METHODS: We retrospectively studied the real-world data of one comprehensive stroke center in mainland China from January to February 2020 and compared it with the data collected during the same period in 2019. We analyzed DTN time, onset-to-door time, severity, effects after treatment, the hospital length of stays, costs of hospitalization, etc., and the correlation between medical burden and prognosis of acute ischemic stroke (AIS) patients. RESULTS: The COVID-19 pandemic was most severe in mainland China in January and February 2020. During the pandemic, there were no differences in pre-hospital or in-hospital workflow metrics (all p>0.05), while the degree of neurological deficit on admission and at discharge, the effects after treatment, and the long-term prognosis were all worse (all p<0.05). The severity and prognosis of AIS patients were positively correlated with the hospital length of stays and total costs of hospitalization (all p<0.05). CONCLUSIONS: COVID-19 pandemic is threatening the stroke care systems. Measures must be taken to minimize the collateral damage caused by COVID-19.

Aberrant microstructural integrity of white matter in mild and severe orthostatic hypotension: A NODDI study.

OBJECTIVE: Scarce evidence is available to elucidate the association between the abnormal microstructure of white matter (WM) and cognitive performance in patients with orthostatic hypotension (OH). This study investigated the microstructural integrity of WM in patients with mild OH (MOH) and severe OH (SOH) and evaluated the association of abnormal WM microstructure with the broad cognitive domains and cognition-related plasma biomarkers. METHODS: Our study included 72 non-OH (NOH), 17 MOH, and 11 SOH participants. Across the groups, the WM integrity was analyzed by neurite orientation dispersion and density imaging (NODDI), and differences in WM microstructure were evaluated by nonparametric tests and post hoc models. The correlations between WM microstructure and broad cognitive domains and cognition-related plasma biomarkers were assessed by Spearman's correlation analysis. RESULTS: The abnormal WM microstructure was localized to the WM fiber bundles in MOH patients but distributed widely in SOH cohorts (p < 0.05). Further analysis showed that the neurite density index of the left cingulate gyrus was negatively associated with amyloid ß-40, glial fibrillary acidic protein, neurofilament light chain, phospho-tau181 (p < 0.05) but positively with global cognitive function (MOCA, MMSE, AER-III), memory, attention, language, language fluency, visuospatial function and amyloid ß-40 / amyloid ß-42 (p < 0.05). Additionally, other abnormal WM microstructures of OH were associated with broad cognitive domains and cognition-related plasma biomarkers to varying degrees. CONCLUSION: The findings evidence that abnormal WM microstructures may present themselves as early as in the MOH phase and that these structural abnormalities are associated with cognitive functions and cognition-related plasma biomarkers.

Distance-based novelty detection model for identifying individuals at risk of developing Alzheimer's disease.

Introduction: Novelty detection (ND, also known as one-class classification) is a machine learning technique used to identify patterns that are typical of the majority class and can discriminate deviations as novelties. In the context of Alzheimer's disease (AD), ND could be employed to detect abnormal or atypical behavior that may indicate early signs of cognitive decline or the presence of the disease. To date, few research studies have used ND to discriminate the risk of developing AD and mild cognitive impairment (MCI) from healthy controls (HC). Methods: In this work, two distinct cohorts with highly heterogeneous data, derived from the Australian Imaging Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing project and the Fujian Medical University Union Hospital (FMUUH) China, were employed. An innovative framework with built-in easily interpretable ND models constructed solely on HC data was introduced along with proposing a strategy of distance to boundary (DtB) to detect MCI and AD. Subsequently, a web-based graphical user interface (GUI) that incorporates the proposed framework was developed for non-technical stakeholders. Results: Our experimental results indicate that the best overall performance of detecting AD individuals in AIBL and FMUUH datasets was obtained by using the Mixture of Gaussian-based ND algorithm applied to single modality, with an AUC of 0.8757 and 0.9443, a sensitivity of 96.79% and 89.09%, and a specificity of 89.63% and 90.92%, respectively. Discussion: The GUI offers an interactive platform to aid stakeholders in making diagnoses of MCI and AD, enabling streamlined decision-making processes. More importantly, the proposed DtB strategy could visually and quantitatively identify individuals at risk of developing AD.

Changes in levels of hypoxia-induced mediators in rat hippocampus during chronic cerebral hypoperfusion.

The hypoxia-inducible factor (HIF)-mediated signaling pathway is an adaptive and protective mechanism that is triggered by hypoxia, ischemia, and other pathophysiological conditions. The expression of HIF-1α and downstream genes, some of which are pro-apoptotic whereas others are pro-survival, is up-regulated in ischemic stroke. Interestingly, however, the effects of HIF-1α activation are different in the early and late stages of acute cerebral ischemia, and these differences may depend on the duration and severity of hypoxia. Therefore, in the present study, we investigated the effect of HIF-1α activation in chronic cerebral hypoperfusion, which plays an important role in the development of dementia. Permanent bilateral common carotid artery occlusion (2VO) was used to induce chronic global cerebral hypoperfusion in rats. The expression of HIF-1α protein and the transcription of downstream genes were measured at different time points, including 0 h, 12 h, 24 h, 3 days, 7 days, 14 days, 28 days, 42 days, and 56 days after 2VO. HIF-1α increased as early as 12 h after the occlusion and remained high for at least 56 days. Interestingly, mRNA levels of both pro-apoptotic (Bcl-2/adenovirus EIB 19 kDa-interacting protein 3, NADPH oxidase activator 1, and NIP3-like protein X) and pro-survival (vascular endothelial growth factor, glucose transporter-1) genes were up-regulated at the early stage after 2VO, followed by a gradual decline to baseline/control levels. Thus, HIF-1α increased consistently during chronic cerebral hypoperfusion, whereas both pro-apoptotic and pro-survival downstream genes were up-regulated only early after 2VO. This mismatch in gene expression may contribute to the lack of a protective effect of highly expressed HIF-1α during the chronic stage of cerebral hypoperfusion.

[Association of estrogen receptor ß gene polymorphisms with hypertension in postmenopausal women].

OBJECTIVE: To explore the association between estrogen receptor ß (ERß) gene polymorphisms and hypertension in postmenopausal women. METHODS: The relationship of two polymorphisms (rs944050 and rs4986938) with hypertension was examined in 71 postmenopausal women with hypertension and 50 healthy age-matched controls. RESULTS: In hypertension and control groups, the ERß allelic frequencies of A and G were 0.500, 0.500, 0.540, 0.460; 0.077, 0.923, 0.170, 0.830 respectively. The genotypic distributions of both polymorphisms stayed within Hardy-Weinberg equilibrium. For polymorphism rs4986938, statistical difference existed between the wild-type genotype and a combination of heterozygous and homozygous variant genotypes (P < 0.05). The variant allele A of rs4986938 in ERß gene decreased the risk of hypertension (OR = 0.41, 95%CI 0.18-0.92). CONCLUSION: The polymorphism rs4986938 in ERß gene was associated with an elevated risk of hypertension in Chinese Han postmenopausal women.

Loss of cannabinoid receptor 2 promotes α-Synuclein-induced microglial synaptic pruning in nucleus accumbens by modulating the pCREB-c-Fos signaling pathway and complement system.

The disruption of nucleus accumbens (NAc) function impacts mood and learning behavior in α-Synucleinopathy, in which microglial synaptic pruning plays a pivotal role in modulating the neuropathologic progression. Available literature documents that in microglia, the activation of cannabinoid receptor 2 (CB2R) decreases inflammation, but it remains obscured regarding the roles of CB2R in microglia-mediated synaptic pruning in the NAc during the neuropathological progression of α-Synucleinopathy. We adopted the fibrillar α-Synuclein (α-Syn) treatment to characterize the effect of genetic CB2R deletion on microglial function and the signaling pathway. CB2R knockout (CB2-/-) mice and wild-type (CB2+/+) mice were divided into the α-Syn or saline treatment groups. Biochemical and microscopy approaches, including immunofluorescence, real-time PCR, and western blotting, were employed to assess the changes in homeostasis of synaptic pruning in NAc under the α-Syn-induced microglia. Moreover, the underlying mechanisms of CB2R on α-Syn induced microglial activity was assessed in vitro. After the injection of α-Syn into the NAc, distinct microglial morphological changes and M1 phenotype transformation were observed between CB2-/- and CB2+/+ mice. Meanwhile, after the α-Syn treatment, CB2-/- mice showed an increased upregulation of CD68 protein and IL-1ß mRNA but decreased brain-derived neurotrophic factor (BDNF) and TGF-ß mRNA compared with CB2+/+ mice. Additionally, CB2-/- microglia after the treatment showed a highly enriched complement 3a receptor (C3aR) producing excessive pruning of cholinergic synapses but less engulfment of dopaminergic synapses. Mechanistically, the loss of CB2R function in the α-Syn stimulation triggered c-Fos activation in microglia, but not in neurons. Further inhibition of microglial CB2R functions under α-Syn stimulation activated the phosphorylated cAMP-response element-binding protein (pCREB)-c-Fos, which was closely related to the C3aR upregulation. Our results reveal a critical and mechanistic role of CB2R in altering the microglial function and its value in the homeostasis of synaptic circuits in the NAc under the α-Syn pathology.

Association of estrogen receptor ß gene polymorphisms with vascular dementia in women.

The objective of the present study was to explore a potential association between the estrogen receptor ß (ERß) gene polymorphisms and vascular dementia (VaD) in women. The relationship of two polymorphisms (rs944050 and rs4986938) and their associated haplotypes in the ERß gene with VaD were examined in 121 Chinese Han women (>50 years of age) including 61 with VaD and 60 healthy age-matched controls. The potential associations were evaluated using unconditional logistic regression. The variant allele G of rs944050 in the ERß gene increased the risk of VaD (odds ratio = 2.02, 95% confidence interval = 1.08-3.77). In haplotype analyses, the ERß haplotype containing the polymorphism rs944050 variant allele and the polymorphism rs4986938 wild-type allele was associated with VaD (odds ratio = 1.70, 95% confidence interval = 1.03-2.84). The polymorphism rs944050 in the ERß gene was associated with an increased risk of VaD in Chinese Han women. Further studies regarding the association between the ERß gene polymorphisms and VaD are needed to confirm these findings.

Wearable knee joint fatigue estimating system based on curvature and pressure sensing.

BACKGROUND: The injury of the knee joint is found to be directly related to the fatigue caused by excessive exercise. Many previous studies used wearable devices to measure the angle of knee joint during activities, but did not pay enough attention to the load of knee joint related to the fatigue degree of it. OBJECTIVE: A wearable embedded system was designed to sense the motion state and load of knee joint and uses the sensoring data to estimate and predict the fatigue degree of knee joint during exercise in real time, so as to prevent it from being injured. METHODS: An economical wearable system is designed to measure the parameters of the knee joint during exercises. Then the warning message and recommended healthy lasting time are able to be sent to users to avoid excessive exercise. 24 healthy volunteers aged 20-25 years were involved in the experiments. Two famous evaluation scales for knee joint from Department of Orthopedics (Lysholm score and IKDC score) were adopted to evaluate the protective effect. RESULTS: After 14 days of the first stage testing, all the participants with wearable devices reported healthy knee joint state to verify the effectiveness of the system. For the second stage, the testing group equipped with wearable warning devices did not receive obvious change in the two scales. However, Lysholm score of control group dropped by at least 7.4 and IKDC score dropped by at least 11.1 which were significantly reduced. CONCLUSION: Only using human perception to prevent knee joint fatigue had a risk of failure while the designed wearable system could protect the knee successfully from injuries during exercises, such as running, badminton, table tennis and basketball. Moreover, female gender and a high BMI value may be two factors that increase the risk of knee injuries during sports.

Prediction of Alzheimer's Disease Using Patterns of Methylation Levels in Key Immunologic-Related Genes.

BACKGROUND: DNA methylation is expected to become a kind of new diagnosis and treatment method of Alzheimer's disease (AD). Neuroinflammation- and immune-related pathways represent one of the major genetic risk factors for AD. OBJECTIVE: We aimed to investigate DNA methylation levels of 7 key immunologic-related genes in peripheral blood and appraise their applicability in the diagnosis of AD. METHODS: Methylation levels were obtained from 222 participants (101 AD, 72 MCI, 49 non-cognitively impaired controls). Logistic regression models for diagnosing AD were established after least absolute shrinkage and selection operator (LASSO) and best subset selection (BSS), evaluated by respondent working curve and decision curve analysis for sensitivity. RESULTS: Six differentially methylated positions (DMPs) in the MCI group and 64 in the AD group were found, respectively. Among them, there were 2 DMPs in the MCI group and 30 DMPs in the AD group independent of age, gender, and APOE4 carriers (p <  0.05). AD diagnostic prediction models differentiated AD from normal controls both in a training dataset (LASSO: 8 markers, including methylation levels at ABCA7 1040077, CNR1 88166293, CX3CR1 39322324, LRRK2 40618505, LRRK2 40618493, NGFR 49496745, TARDBP 11070956, TARDBP 11070840 area under the curve [AUC] = 0.81; BSS: 2 markers, including methylation levels at ABCA7 1040077 and CX3CR1 39322324, AUC = 0.80) and a testing dataset (AUC = 0.84, AUC = 0.82, respectively). CONCLUSION: Our work indicated that methylation levels of 7 key immunologic-related genes (ABCA7, CNR1, CX3CR1, CSF1R, LRRK2, NGFR, and TARDBP) in peripheral blood was altered in AD and the models including methylation of immunologic-related genes biomarkers improved prediction of AD.

CX3C-chemokine receptor 1 modulates cognitive dysfunction induced by sleep deprivation.

BACKGROUND: Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. METHODS: Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. RESULTS: CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. CONCLUSIONS: These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

Development and application of a Chinese Version of the Language Screening Test (CLAST) in post-stroke patients.

Aphasia shows high incidence in stroke patients and seriously impairs language comprehension, verbal communication, and social activities. Therefore, screening aphasic patients during the acute phase of stroke is crucial for language recovery and rehabilitation. The present study developed a Chinese version of the Language Screening Test (CLAST) and validated it in post-stroke patients.The CLAST was adapted from the Language Screening Test developed by Constance et al to incorporate Chinese cultural and linguistic specificities, and administered to 207 acute stroke patients and 89 stabilized aphasic or non-aphasic patients. Based on the Western Aphasia Battery (WAB) test, its reliability and validity were assessed. A cut-off for the CLAST in Chinese patients was determined by ROC curve analysis.The CLAST comprised 5 subtests and 15 items, including 2 subscores, namely expression (8 points, assessing naming, repetition, and automatic speech) and receptive (7 points maximum, evaluating picture recognition, and verbal instructions) indexes. Analysis of the alternate-form reliability of the questionnaire showed a retest correlation coefficient of 0.945 (P < .001). Intraclass correlation coefficients of three rating teams were >0.98 (P < .001). Internal consistency analysis showed a Cronbach's alpha coefficient of 0.909 (P < .001). The non-aphasia group showed higher scores than the aphasia group (14.2 ±â€Š1.3 vs 10.6 ±â€Š3.8) (P < .01). The questionnaire showed good construct validity by factor analysis. ROC curve analysis showed high sensitivity and specificity for the CLAST, with a cut-off of 13.5.The CLAST is suitable for Chinese post-stroke patients during the acute phase, with high reliability, validity, sensitivity, and specificity.

Risk Factors for Aphasia in Cerebral Small Vessel Diseases.

BACKGROUND: Lacunes and white matter hyperintensities (WMH) are two common findings seen on neuroimaging in patients with cerebral small vessel disease (cSVD). Clinically we observed that some patients with cSVD have aphasia through the language assessment scale. Our study aimed to explore the underlying risk factors for aphasia in cSVD patients. METHODS: This study retrospectively analyzed 38 patients, with and without aphasia, aged 50 or over, Chinese Han population, diagnosed as cSVD with lacunes and/or WMH. We collected demographic characteristics and vascular risk factors. The severity of WMH was assessed by the age related white matter changes (ARWMC) rating scale. RESULTS: Risk factors associated with aphasia were: lower education (p = 0.029), higher total cholesterol (TC) levels (p = 0.023), and higher low-density lipoprotein cholesterol (LDL-C) levels (p = 0.027). After controlling for age and sex, levels of TC (odds ratios, 1.96; 95% confidence interval, 1.06-3.62; p = 0.032) remained associated with aphasia independently. CONCLUSION: High level of TC was significantly associated with a higher risk of aphasia in clinically silent cSVD patients. Early interventions including lipid-lowering treatment, cranial magnetic resonance imaging (MRI) and ARWMC rating scale should be performed. Further studies are needed to explore proper methods of prevention and treatment for aphasia in clinically silent cSVD patients, in addition to understanding the pathophysiological mechanism.

Abnormal resting-state functional connectivity in posterior cingulate cortex of Parkinson's disease with mild cognitive impairment and dementia.

OBJECTIVE: To investigate changes in the functional connectivity (FC) pattern in the posterior cingulate cortex (PCC) of Parkinson's disease (PD) patients with mild cognitive impairment and dementia by employing resting-state functional magnetic resonance imaging (RS-fMRI). METHODS: Twenty-seven PD patients with different cognitive status and 9 healthy control subjects (control group) were enrolled for RS-fMRI. The RS-fMRI data were analyzed with DPARSF and REST software. Regions with changed functional connectivity were determined by the seed-based voxelwise method and compared between groups. Correlation between the intensity of FC and the MoCA scores of PD group was analyzed. RESULTS: Parametric maps showed statistical increases in PCC functional connectivity in PD-MCI patients and decreases in PCC connectivity in PDD patients. The latter group of patients also showed evidence for increased connectivity between prefrontal cortices and posterior cerebellum. A significant positive correlation was found between the MoCA scores and the strength of PCC connectivity in the angular gyrus and posterior cerebellum and a negative correlation between MoCA scores and PCC connectivity in all other brain regions. CONCLUSION: When patients transition from PD-NCI to PD-MCI, there appears to be an increase in functional connectivity in the PCC, suggesting an expansion of the cortical network. Another new network (a compensatory prefrontal cortical-cerebellar loop) later develops during the transition from PD-MCI to PDD.

Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose deprivation and reoxygenation in human brain microvascular endothelial cells.

Cerebral ischemia/reperfusion (I/R) injury leads to brain vascular dysfunction, which is characterized by endothelial cell injury or death. Long noncoding (lnc) RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reportedly associated with endothelial cell functions and dysfunctions. In the present study, the role of MALAT1 in I/R-induced cerebral vascular endothelial cell apoptosis was explored using oxygen-glucose deprivation and reoxygenation (OGD-R) as an in vitro I/R injury model. Primary human brain microvascular endothelial cells were cultured under OGD-R, and the expression levels of MALAT1 and cell apoptosis were measured at 6, 9, 12, 24 and 36 h post-reoxygenation. The expression levels of MALAT1 and the apoptotic rate of cells exposed to OGD-R exhibited contrasting trends following reoxygenation. Following OGD-R, lentiviral overexpression of MALAT1 increased phosphatidylinositol 3-kinase (PI3K) activities and the activation of Akt phosphorylation, and decreased cell apoptosis and caspase 3 activities, which were successfully abolished by treatment with a PI3K inhibitor, Wortmannin. Conversely, lentiviral knockdown of MALAT1 decreased PI3K activities and the activation of Akt phosphorylation, and increased cell apoptosis and caspase 3 activity. Overexpression and knockdown of MALAT1 exhibited no significant effects on OGD-R-induced reactive oxygen species (ROS) production. In conclusion, to the best of our knowledge, the present study was the first to suggest that lncRNA MALAT1 may protect human brain vascular endothelial cells from OGD-R-induced apoptosis via a PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential novel therapeutic target for cerebral I/R injury.

Cognitive Improvement Induced by Environment Enrichment in Chronic Cerebral Hypoperfusion Rats: a Result of Upregulated Endogenous Neuroprotection?

Environment enrichment (EE) has been demonstrated to improve the cognitive impairment that is induced by chronic cerebral hypoperfusion (CCH), but the underlying mechanism has not yet been elucidated. This study aimed to investigate the role of endogenous neuroprotection in EE-induced cognitive improvement in rats with CCH. Permanent bilateral common carotid artery occlusions (2-vessel occlusions (2VOs)) were performed to induce CCH in male adult Wistar rats. Four weeks after the surgeries, the rats were exposed to enriched environments for 4 weeks (6 h/day). Subsequently, we assessed the effects of EE on cognitive function, brain histone acetylation levels, neuroprotection-related transcription factors (i.e., cAMP response element-binding protein (CREB), phospho-CREB (p-CREB), hypoxia-inducible factor 1 (HIF-1) α, and nuclear regulatory factor 2 (Nrf2)), and oxidative stress and histological changes in the brain. After 2VO, the rats exposed to the EE treatment exhibited increased acetylation of histone 4 and increased p-CREB and Nrf2 protein levels in the brain. HIF-1α levels were increased after 2VO and reduced after EE treatment. The oxidative damage, histopathological changes in the brain, and spatial learning and memory impairments induced by 2VO were subsequently restored after EE treatment. These data indicate that EE promotes the acetylation of histone 4, regulates some neuroprotection-related transcription factors, attenuates oxidative damage, and protects against the histopathological damage to the brain induced by CCH. Together, the effects of EE in CCH rats might contribute to the recovery of spatial learning and memory.

Radix Angelica Sinensis that contains the component Z-ligustilide promotes adult neurogenesis to mediate recovery from cognitive impairment.

Radix Angelica Sinensis (RAS) has beneficial effects in patients suffering from cognitive impairment associated with chronic cerebral hypoperfusion. It has previously been demonstrated that RAS prevents the neurotoxic effects of ß-amyloid (Aß) in vitro, protects from injuries due to oxidative stress, inflammation and apoptosis and ameliorates scopolamine-induced amnesia in rats. Here, we studied the effects of RAS on cognitive improvement and neurogenic enhancement and examined the possible underlying mechanisms in a rat model with permanent bilateral common carotid artery occlusion, which serves as a model of chronic cerebral hypoperfusion-related neurodegenerative diseases. RAS enhances adult neurogenesis in the hippocampus following chronic cerebral hypoperfusion and improves the cognitive decline associated with hypoperfusion. Long-term ablation of adult hippocampal neurogenesis through cranial irradiation abolishes the protective effects of RAS on cognition. Furthermore, administration of RAS restores the decrease of brain-derived neurotrophic factor (BDNF) expression, the phosphorylation of cAMP-responsive element binding protein (CREB) and the glutamic acid decarboxylase 65 (GAD65) staining intensity in rats with chronic cerebral hypoperfusion. The present study supports the hypothesis that adult neurogenesis is required for RAS to facilitate recovery from the cognitive impairment induced by chronic cerebral hypoperfusion, while neurogenic enhancement secondary to RAS treatment may be due to increased BDNF and phosphorylated cAMP-responsive element binding protein (p-CREB) levels and increased γ-aminobutyric acid (GABA) expression. Based on the possible mechanisms suggested by the present study, this well-known traditional medicine may represent a candidate therapeutic agent for the treatment of dementia associated with vascular injury.