Nov 2017, Volume 2 Issue 3

    
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  • Review
    Perspectives on a collaborative Canada-China research program on diagnostic biomarkers for pre-dementia stages of Alzheimer’s disease
    Serge Gauthier, Jianping Jia, Sylvie Belleville, Simon Cloutier, Dessa Sadovnick, Colleen Guimond, Laura Robb, Mario Masellis, Guy A Rouleau, Liyong Wu, Pedro Rosa-Neto
    Journal of Translational Neuroscience. 2017, 2 (3) : 1-6. https://doi.org/10.3868/j.issn.2096-0689.2017.03.001
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    As biomarkers are important in the early diagnosis of Alzheimer's disease (AD), the first collaborative work of recruiting early-onset familial AD (EOFAD) families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsychological tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment (MCI) stages of AD. Besides identifying pedigrees with novel mutations in presenilins (PSENs)/amyloid precursor protein (APP), the program has benefited training of Chinese research fellows, AD clinical trials for prevention, the ethical concerns for clinical findings, and other collaborative projects with Chinese investigators. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.
  • Review
    Hypertension and Alzheimer’s disease
    Yue Fu, Jianping Jia
    Journal of Translational Neuroscience. 2017, 2 (3) : 7-14. https://doi.org/10.3868/j.issn.2096-0689.2017.03.002
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    Alzheimer’s disease (AD) accounts for 60% to 80% of dementia cases and is the most common cause of dementia. In the past decade, studies have shown a close association between blood pressure and AD. It is found that elevated blood pressure at midlife would increase the risk of dementia, including AD. However, there is no definitive conclusion about the relationship between elderly blood pressure and cognitive function. Abnormal pulse pressure may also increase the risk of dementia. The impact of antihypertensive drugs is inconclusive, and the mechanism of their protection of cognitive function is not clear.
  • Review
    Recommendation for and comparison of three types of dementia: Alzheimer’s disease, subcortical ischemic vascular dementia, and mixed dementia
    Lu Shi, Jianping Jia
    Journal of Translational Neuroscience. 2017, 2 (3) : 15-25. https://doi.org/10.3868/j.issn.2096-0689.2017.03.003
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    With the progress in global demography of aging, dementia has become a great world health-care issue that require urgent attention and settlement. Dementia can arise from a variety of factors, such as neuronal degeneration for Alzheimer’s disease (AD), vascular risk factors and multiple infarcts for vascular dementia (VaD), and both degeneration and vascular factors for mixed dementia (MD). Pathophysiology of AD includes the amyloid and tau protein hypothesis, and inflammation-related mechanisms are also widespread mentioned. Subcortical ischemic vascular dementia (SIVD), a subtype of VaD, is commonly caused by complete or incomplete lacunar infarction of VaD pathology. MD involves both degeneration and vascular factors, and the interaction between the two results in the complication of the pathological mechanism and clinical phenotype. The clinical manifestations of AD are often divided into four stages according to the progress of the disease, while the phenotypes of SIVD usually has two categories. As for MD, the phenotypes are complex and diverse. Several clinical studies showed that its symptoms and signs are more similar to SIVD than AD. This article aims to analyze and compare the different aspects of the three kinds of dementia.
  • Review
    Homocysteine and Alzheimer’s disease: a literature review
    Jianwei Yang, Jianping Jia
    Journal of Translational Neuroscience. 2017, 2 (3) : 26-30. https://doi.org/10.3868/j.issn.2096-0689.2017.03.004
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    Increasing evidence in recent years suggests homocysteine (Hcy) is involved in the pathogenesis of Alzheimer’s disease (AD), and that modifying this risk factor may be an alternative approach to delaying or preventing onset of this disease. However, intervention studies suggest inconsistent effects of folic acid supplementation, with or without vitamin B12, on the prevention of incident AD. Studies with Hcy-lowering therapy show beneficial effects of B vitamins in patients with mild cognitive impairment (MCI), especially in those with high Hcy levels. Further studies are needed to confirm elevated Hcy levels as a potentially treatable risk factor for AD.
  • Review
    Efficacy and pharmacogenomics of donepezil
    Xiu Wang, Jianping Jia
    Journal of Translational Neuroscience. 2017, 2 (3) : 31-38. https://doi.org/10.3868/j.issn.2096-0689.2017.03.005
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    With the aging of society, dementia has become a more and more serious social problem. Alzheimer’s disease (AD) is a major cause of dementia, and there is no drug to reverse the disease progression. Donepezil is the main drug currently in symptomatic treatment. However, the efficacy of donepezil was moderate, with the patient variably responding to the treatment with donepezil. The commonest adverse events in the treatment were nausea, vomiting and diarrhea; QT prolongation rarely occurred. Many patients gave up treatment because of adverse events or lack of efficacy. Pharmacogenomics is developed on the basis of pharmacogenetics, by studying the polymorphisms in genes involved in drug metabolic enzymes, transporter and drug receptor, to guide individualized treatment. In terms of the pharmacogenomics on the efficacy of donepezil, there is no clear conclusion except CYP2D6 genotype affecting drug clearance.
  • Research Article
    Disrupted functional connectivity of default mode network and executive control network in patients with vascular cognitive impairment, no dementia
    Tan Zhao, Jianping Jia
    Journal of Translational Neuroscience. 2017, 2 (3) : 39-48. https://doi.org/10.3868/j.issn.2096-0689.2017.03.006
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    Objective: To investigate functional connectivity within default mode network (DMN) and executive control network (ECN) in vascular cognitive impairment, no dementia (VCIND). Methods: Twenty-eight VCIND patients and sixteen healthy controls were recruited. A seed-based connectivity analysis was performed using data from resting-state functional magnetic resonance imaging (fMRI). Based on previous findings, posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) were chosen as regions of interest to study these networks. One-sample t-test and two-sample t-test were used for statistical analysis. Results: Compared with the controls, the VCIND group exhibited increased functional activity in such DMN regions as the left inferior temporal gyrus, parahippocampal gyrus, and medial frontal gyrus. The VCIND group had decreased functional connectivity of DMN at right superior frontal gyrus, left mid-cingulate area, the medial part of left superior frontal gyrus, and bilateral medial frontal gyrus. The VCIND group also showed decreased functional connectivity of ECN primarily at left inferior parietal gyrus, right angular gyrus, right middle occipital gyrus, and right middle frontal cortex. Conclusions: Increased functional connectivity within DMN and decreased functional connectivity within ECN suggested dysfunction of these two networks, which might be associated with the cognitive deficits in patients with VCIND. These findings may help us understand the pathogenesis and clinical characteristics of VCIND.