Insights on the pathophysiology of Alzheimer's disease: The crosstalk between amyloid pathology,neuroinflammation and the peripheral immune system

Alzheimer's disease (AD) is the most common form of dementia, whose prevalence is growing along with the increased life expectancy. Although the accumulation and deposition of amyloid beta (Aβ) peptides in the brain is viewed as one of the pathological hallmarks of AD and underlies, at least in part, brain cell dysfunction and behavior alterations, the etiology of this neurodegenerative disease is still poorly understood. Noticeably, increased amyloid load is accompanied by marked inflammatory alterations, both at the level of the brain parenchyma and at the barriers of the brain. However, it is debatable whether the neuroinflammation observed in aging and in AD, together with alterations in the peripheral immune system, are responsible for increased amyloidogenesis, decreased clearance of Aβ out of the brain and/or the marked deficits in memory and cognition manifested by AD patients. Herein, we scrutinize some important traits of the pathophysiology of aging and AD, focusing on the interplay between the amyloidogenic pathway, neuroinflammation and the peripheral immune system.     

Body mass index (BMI) at an early age and the risk of dementia

BMI change and BMI at an early age have not been investigated as risks for dementia. This case-control study included 286 dementia patients and 268 controls from two medical centers between 2007 and 2009. BMI information was collected from medical records and questionnaires. Men and women with low BMIs at the time of the study, in their 20s, and in their 40s had significantly increased risks of Alzheimer's disease (AD) (odds ratio = OR = 2.62–3.97) and increased vascular dementia (VaD) risk (20s and 40s: OR = 6.23–11.11) compared with those with normal BMIs. High BMI in the 20s and 40s was associated with increased VaD risk (OR = 15.29 and 10.32) among women. For BMI changes from the 20s or 40s, the second and third tertiles were significantly associated with decreased AD risk among women (OR = 0.15–0.35) compared to the first tertile. The third tertile of BMI change from the 20s or 40s was associated with decreased VaD risk among women (OR = 0.06 and 0.14). Low BMIs in the 20s and 40s were stronger predictors of AD and VaD. There was a U-shaped association between BMI at different ages and dementia among participants with VaD.     

Association Between Family History and Hypertension Among Chinese Elderly

This study aimed to evaluate the association between family history and prevalence of hypertension among Chinese community elderly, and also explore the gender difference.A population-based cross-sectional study was conducted in Miyun district of Beijing, in 2014. The family history information was obtained from each subject and was divided into 3 categories, no family history (FH0), 1 generation of first-degree relatives with hypertension (FH1), and 2 generations of first-degree relatives with hypertension (FH2).The prevalence of hypertension was 53.0%. Participants with positive family history had a significantly higher prevalence of hypertension (67.5%, 95% CI: 63.3–71.7) than those without (47.9%, 95% CI: 45.2–50.6), and even among participants without hypertension, the blood pressure levels were higher with positive FH. Multiple logistic regression analysis showed that a significantly linear-trend increase in hypertension according to family history of first degree relative numbers was observed in both genders (P for trend < 0.001).This study suggests that family history had not only a significant but also graded association with hypertension and with blood pressure levels, and this association exists even among those without hypertension.     

胰岛素诱导因子2基因rs7566605位点对中国老年人群肥胖及血脂影响

目的 探索胰岛素诱导因子2（insulin-induced gene 2,INSIG2） 基因多态性rs7566605 在中国人群中与肥胖及血脂代谢的关系。 方法 收集2009 年9 月- 2010 年6 月参加并完成北京市老年人健康调查的2 014 例样本,内容包括身体测量指标、血生化指标及环境因素并提取全部样本DNA,利用芯片技术进行基因分型。观察所有参与者基本健康情况并分析不同rs7566605 基因型与肥胖及血脂代谢异常疾病之间的关联。 结果 INSIG2 基因上游多态性rs7566605 C 位点与男性血清甘油三酯水平升高（P =0.029） 及男女合并样本的血清高密度脂蛋白胆固醇（high-density lipoprotein cholesterol,HDL-C） 降低（P =0.029） 关联存在统计学意义,并且可能增加高甘油三酯血症（P =0.019,OR=1.175） 和低高密度脂蛋白血症（P =0.020,OR=1.178） 患病风险。杂合共显性模型可能是主要遗传模式。本人群中未发现该位点与体质量指数或肥胖关联存在统计学意义。 结论 rs7566605 可能与中国老年人群与脂类代谢相关,未发现与肥胖相关联。     

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.

某体检人群血压水平与颈动脉斑块相关性的横断面研究

目的探讨血压水平与颈动脉斑块患病风险的相关性。方法选取2017年在解放军总医院第四医学中心进行颈部超声检查的某单位体检人群为研究对象,采集血压等生理、生化指标。将血压指标按连续变量(收缩压、舒张压和脉压差)和分类变量(是否高血压、血压分级和脉压差四分类)进行分析,采用Logistic回归模型分析该人群血压水平与颈动脉斑块的关联性。结果共纳入研究对象716名,其中男性321名(44.8%),女性395名(55.2%),高血压和颈动脉斑块的患病率分别为40.9%(293例)和40.4%(289例)。≥60岁、糖尿病、高血压以及腰围增加、收缩压、空腹血糖、糖化血红蛋白升高者的颈动脉斑块患病率更高(P<0.05)。随着血压分级和脉压差四分类水平的升高,颈动脉斑块患病风险呈现增高趋势(Ptrend<0.05)。Logistic回归模型分析结果显示,收缩压每升高1 mmHg使颈动脉斑块的患病风险增加了1.4%(95%CI:1.005~1.024);以非高血压人群为对照组,高血压人群的颈动脉斑块的患病风险增加了62.9%(95%CI:1.146~2.316),其中,女性高血压人群的颈动脉斑块患病风险增加106.3%(95%CI:1.242~3.427);以正常血压人群为对照组,正常高值、1级高血压、2和3级高血压的颈动脉斑块的患病风险分别增加了86.8%(95%CI:1.175~2.946)和84.8%(95%CI:1.098~3.110)和119.6%(95%CI:1.165~4.142);以脉压差<60 mmHg(1 mmHg=0.133 kPa)人群为对照组,脉压差≥60 mmHg组的颈动脉斑块的患病风险增加56.2%(95%CI:1.049~2.326),其中女性脉压差≥60 mmHg人群的颈动脉斑块风险增加了73.3%(95%CI:1.007~2.983);以脉压差四分类Q1(≤42 mmHg)人群为对照组,Q3(50~61 mmHg)和Q4(≥62 mmHg)人群颈动脉斑块的患病风险分别增加了92.2%(95%CI:1.173~3.149)和95.0%(95%CI:1.147~3.316)。结论血压和脉压差水平升高与颈动脉斑块患病风险升高相关联,防控血压和脉压差升高可能是防控颈动脉斑块的有效措施之一。     

The association between BMI and metabolically unhealthy status with COVID-19 mortality: Based on 3019 inpatients from Wuhan,China

Background and aimsPatients with multiple metabolic diseases are at high risk for the occurrence and death of COVID-19. Little is known about patients with underweight and metabolically healthy obesity. The aim of this study is to evaluate the impact of BMI and COVID-19 mortality in hospitalized patients, and also explore the association in different metabolically healthy (MHS) and unhealthy status (MUS).Methods and resultsA retrospective cohort study based on 3019 inpatients from Wuhan was conducted. Included patients were classified into four groups according the BMI level (underweight, normal weight, overweight and obesity), and patients with at least one of the metabolic abnormalities (diabetes, hypertension, dyslipidemia) was defined as MUS. Multiple Cox model was used to calculate the hazard ratio (HR). Compared to patients with normal weight, the HRs of overweight and obesity for COVID-19 mortality were 1.91 (95%CI:1.02–3.58) and 2.54 (95%CI:1.22–5.25) respectively in total patients, and 2.58 (95%CI:1.16–5.75) and 3.89 (95%CI:1.62–9.32) respectively in the elderly. The HR of underweight for COVID-19 mortality was 4.58 (95%CI:1.56–13.48) in the elderly. For different metabolic statuses, both underweight, overweight and obesity had obviously negative association with COVID-19 mortality in total and elderly patients with MUS. However, no significance was found in non-elderly and patients with MHS.ConclusionNot only overweight or obesity, but also underweight can be associated with COVID-9 mortality, especially in the elderly and in patients with MUS. More large-scale studies are needed for patients with underweight and metabolically healthy overweight or obesity.