Yan Lian

Association of Soluble Intercellular Adhesion Molecule 1 with Neurological Deterioration of Ischemic Stroke: The Chongqing Stroke Study

Background: Adhesion molecules play important roles in the pathophysiology of ischemic stroke. The aim of the present study was to investigate whether serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cellular adhesion molecule 1 (sVCAM-1) and soluble E-selectin were associated with neurological deterioration of ischemic stroke. Methods: 238 consecutive patients with ischemic stroke examined within 24 h from onset were enrolled into the study. The stroke severity was daily assessed with the NIH Stroke Scale (NIHSS) within the first week after admission. Serum levels of sICAM-1, sVCAM-1 and sE-selectin after admission were measured using enzyme-linked immunosorbent assay. Multivariate logistic regression was used to analyze the association of serum levels of sICAM-1, sVCAM-1 and sE-selectin on admission with the neurological deterioration of ischemic stroke, adjusted for potential confounders. Results: 52 (21.8%) out of 238 stroke patients suffered from neurological deterioration. Serum levels of sICAM-1 on admission of stroke patients were significantly higher than those of healthy controls. Compared with patients without deterioration, patients with neurological deterioration had higher levels of sICAM-1, but not of sVCAM-1 and sE-selectin. On multivariate logistic regression, the serum level of sICAM-1 on admission was associated with neurological deterioration of stroke (OR 2.92, 95% CI 1.41–6.05). Other variables associated with neurological deterioration were fasting serum glucose (OR 1.65, 95% CI 1.24–2.20), baseline fibrinogen (OR 1.31, 95% CI 1.13–1.52) and NIHSS score (OR 1.23, 95% CI 1.15–1.32). Conclusions: The serum level of sICAM-1 on admission is associated with neurological deterioration of ischemic stroke.

The relationship between single nucleotide polymorphisms of the NTRK2 gene and sporadic Alzheimer's disease in the Chinese Han population

Alzheimers disease (AD) is characterized by the degeneration of basal forebrain cholinergic neurons, whose survival and function are affected by neurotrophins and their receptors. The impaired signaling pathway of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) is considered to play an important role in AD pathogenesis. To explore the association of polymorphisms within the NTRK2 gene (encoding TrkB) and sporadic AD (sAD), a case-control study was conducted in a Chinese Han cohort including 216 sAD patients and 244 control participants. Five single nucleotide polymorphisms (SNPs), with four of them within the promoter region and one in intron, were selected and genotyped with a polymerase chain reaction-ligase detection reaction (PCR-LDR) method. No association was revealed between these SNPs or the haplotypes containing four promoter SNPs and the risk of sAD. The results of this study indicate that polymorphisms in the selected regions of the NTRK2 gene are unlikely to confer the susceptibility of sAD in the Chinese Han population.

General public perceptions and attitudes toward Alzheimer's disease from five cities in China.

Alzheimers disease (AD) is the most common type of dementia affecting the aged population worldwide, yet its social perceptions have been less studied. To investigate the perceptions and attitudes toward AD in the Chinese population, a cross-sectional face-to-face survey of 2,000 randomly selected adults was conducted in five representative cities of China. This survey focused on the fear of AD, and the relationship between this variable and each studied factor was analyzed using univariate analysis and multivariate regression analysis. In general, 76.6% of the total respondents had personal fear of developing AD, and such fear was closely related to the proximity to AD and perceived severity of AD, as well as other factors such as gender and self-perceived health. The results strongly suggested that more attention should be paid to public health education of AD, which can only be achieved with the cooperation of government, media, medical institutions, and the community so as to eliminate peoples confusion about AD, relieve their psychological burden, and optimize their health-seeking behavior.

No association of SORT1 gene polymorphism with sporadic Alzheimer's disease in the Chinese Han population.

Increasing evidence shows that sortilin (encoded by SORT1 gene), a member of the vacuolar protein sorting 10 family of sorting receptors, can modulate amyloid-&bgr; peptides (A&bgr;) metabolism and clearance, as well as mediate the neurotoxicity of the A&bgr; oligomer and proneurotrophins, thus playing diverse roles in the pathogenesis of Alzheimer’s disease. To assess the association between single nucleotide polymorphism (SNP) of the SORT1 gene and sporadic Alzheimer’s disease (sAD) in the Chinese Han population, a case–control study was carried out including 220 sAD patients and 245 controls. One tag SNP was selected from the entire SORT1 gene through construction of linkage disequilibrium blocks, and three SNPs located in the vicinity of SORT1 that affect its expression were also selected. The four target SNPs were genotyped using a multiplex PCR-ligase detection reaction method, yielding no significant association between them or haplotypes containing three of them, and the risk of sAD. The results of this study indicate that polymorphisms of the SORT1 gene are unlikely to confer the risk of sAD in the Chinese Han population.

Adverse life event and risk of cognitive impairment: a 5-year prospective longitudinal study in Chongqing, China

Background and purpose:  Current knowledge of factors that increase or decrease the risk of cognitive impairment in elderly people is limited. Recently adverse life events appeared to be associated with the increased risk of cognitive impairment in elderly people. However, this is less studied. We conducted a 5‐year prospective study to evaluate the association between adverse life events and the risk of cognitive impairment in Chinese elderly people.

Perspectives on the Tertiary Prevention Strategy for Alzheimer's Disease.

Amyloid-beta (Aβ) plays a pivotal role in Alzheimers disease (AD) pathogenesis, and is the most promising disease-modifying target for AD. A succession of failures in Aβ-targeting clinical trials, however, has prompted questions on whether Aβ is the true cause of AD and a valid therapeutic target. Therefore, current therapeutic targets and intervention strategies must be reconsidered. In addition to Aβ, multiple pathological events such as tau hyperphosphorylation, oxidative stress and neuroinflammation are involved in the disease pathogenesis and cause cross-talk between these pathological pathways, which synergistically drive disease progression. Increasing evidence also reveals that the pathogenesis varies at different stages of the disease. Therefore, targeting Aβ alone at all stages of the disease would not be sufficient to halt or reverse disease progression. In the light of the pathophysiologic similarities between the development of ischemic stroke and AD, we can formulate management strategies for AD from the successful practice of ischemic stroke management, namely the tertiary prevention strategy. These new perspectives of tertiary prevention target both Aβ and different pathological pathways of AD pathogenesis at different stages of the disease, and may represent a promising avenue for the effective prevention and treatment of AD.Amyloid-beta (Aβ) plays a pivotal role in Alzheimer’s disease (AD) pathogenesis, and is the most promising disease-modifying target for AD. A succession of failures in Aβ-targeting clinical trials, however, has prompted questions on whether Aβ is the true cause of AD and a valid therapeutic target. Therefore, current therapeutic targets and intervention strategies must be reconsidered. In addition to Aβ, multiple pathological events such as tau hyperphosphorylation, oxidative stress and neuroinflammation are involved in the disease pathogenesis and cause cross-talk between these pathological pathways, which synergistically drive disease progression. Increasing evidence also reveals that the pathogenesis varies at different stages of the disease. Therefore, targeting Aβ alone at all stages of the disease would not be sufficient to halt or reverse disease progression. In the light of the pathophysiologic similarities between the development of ischemic stroke and AD, we can formulate management strategies for AD from the successful practice of ischemic stroke management, namely the tertiary prevention strategy. These new perspectives of tertiary prevention target both Aβ and different pathological pathways of AD pathogenesis at different stages of the disease, and may represent a promising avenue for the effective prevention and treatment of AD.

Identification of a Novel Mutation in the Presenilin 1 Gene in a Chinese Alzheimer’s Disease Family

This study has identified a gene mutation in a Chinese family with Alzheimer’s disease (AD). Family members were screened by a set of medical examinations and neuropsychological tests. Their DNA was extracted from blood cells and sequenced for gene mutation in the amyloid precursor protein (APP), the presenilin 1 (PS1) and the presenilin 2 (PS2) genes. Genetic analysis showed that the AD patients in the family harbored a T to G missense mutation at the position 314 in exon 4 of the PS1 gene, resulting in a change of F105C in amino acid sequence. Clinical manifestation of these patients included memory loss, counting difficulty, personality change, disorientation, dyscalculia, agnosia, aphasia, and apraxia, which was similar to that of the familial AD (FAD) patients harboring other PS1 mutations. We intend to add a novel mutation F105C of the PS1 gene to the pool of FAD mutations. With the current available genetic data, mutations of the PS1 gene account for the majority of gene mutations in Chinese FAD.

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.

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.