APP17肽对卵巢去势大鼠海马神经元凋亡相关因子表达的影响

为研究卵巢去势大鼠海马神经元内凋亡相关因子Fas、Fas L、NFκB、c fos、c Jun的表达及APP1 7肽对这些因子表达的影响 ,将健康雌性Wistar大鼠行双侧卵巢切除手术造模 ,并用APP1 7肽治疗 ,分别用免疫组化方法观察Fas、Fas L、NFκB、c fos、c Jun的表达 ,用TUNEL方法检测神经元的凋亡。结果发现 :卵巢去势大鼠海马神经元Fas、Fas L、c fos、c Jun的表达增高 ,而NFκB的表达则减少 ;使用APP1 7肽治疗后 ,上述蛋白质的表达恢复到正常水平 ,TUNEL检测未发现凋亡神经元。提示卵巢去势大鼠发生了海马神经元的凋亡相关蛋白的改变 ,可能是神经元处于凋亡前状态 ;APP1 7肽可改善卵巢去势大鼠海马神经元内凋亡相关蛋白的表达 ,维持神经元的正常功能     

Genome-wide profiling of blood pressure in adults and children

Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between different age groups, using genome-wide profiling. Single nucleotide polymorphism sets were defined based on a meta-analysis of genome-wide association studies on systolic blood pressure and diastolic blood pressure performed by the Cohort for Heart and Aging Research in Genome Epidemiology (n=29 136), using different P value thresholds for selecting single nucleotide polymorphisms. Subsequently, genetic risk scores for systolic blood pressure and diastolic blood pressure were calculated in an independent adult population (n=2072) and a child population (n=1034). The explained variance of the genetic risk scores was evaluated using linear regression models, including sex, age, and body mass index. Genetic risk scores, including also many nongenome-wide significant single nucleotide polymorphisms, explained more of the variance than scores based only on very significant single nucleotide polymorphisms in adults and children. Genetic risk scores significantly explained ≤1.2% (P=9.6*10(-8)) of the variance in adult systolic blood pressure and 0.8% (P=0.004) in children. For diastolic blood pressure, the variance explained was similar in adults and children (1.7% [P=8.9*10(-10)] and 1.4% [P=3.3*10(-5)], respectively). These findings suggest the presence of many genetic loci with small effects on blood pressure regulation both in adults and children, indicating also a (partly) common polygenic regulation of blood pressure throughout different periods of life.     

中国老年糖尿病诊疗指南(2021年版)

随着我国老龄化的加剧,老年糖尿病的患病率明显增高,亟需对老年糖尿病患者进行规范化管理。国家老年医学中心、中华医学会老年医学分会以及中国老年保健协会糖尿病专业委员会组织专家撰写了《中国老年糖尿病诊疗指南(2021年版)》。本指南共十九章,内容包括老年糖尿病及其并发症的流行病学、临床特点、老年糖尿病患者的健康综合评估、血糖管理、动脉粥样硬化性心血管疾病危险因素管理、急慢性并发症管理、老年糖尿病共患疾病及特殊情况的管理等。本指南强调老年糖尿病患者存在高度异质性,需要综合评估,采取分层和个体化的管理策略。提出了适合老年糖尿病患者的血糖管理路径、简约治疗理念和“去强化治疗策略”。本指南的颁布将有助于指导和帮助临床医师对老年糖尿病患者进行全方位、全周期的规范化综合管理,改善中国老年糖尿病患者的临床结局。     

Prognosis of Mild Cognitive Impairment in General Practice: Results of the German AgeCoDe Study

PURPOSE

The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determinants of the future course of MCI in the AgeCoDe study (German Study on Ageing, Cognition, and Dementia in Primary Care Patients).

METHODS

We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospectively split into 4 groups representing remittent, fluctuating, stable, and progressive courses of MCI. We performed ordinal logistic regression analysis and classification and regression tree (CART) analysis.

RESULTS

Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spectrum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis.

CONCLUSIONS

In primary care, about one-quarter of patients with MCI have progression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.     

Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study

Type 2 diabetes may be a risk factor for dementia, but the associated pathological mechanisms remains unclear. We evaluated the association of diabetes alone or combined with the apolipoprotein E (APOE) gene with incident dementia and neuropathological outcomes in a population-based cohort of 2,574 Japanese-American men enrolled in the Honolulu-Asia Aging Study, including 216 subjects who underwent autopsy. Type 2 diabetes was ascertained by interview and direct glucose testing. Dementia was assessed in 1991 and 1994 by clinical examination and magnetic resonance imaging and was diagnosed according to international guidelines. Logistic regression was used to assess the RR of developing dementia, and log-linear regression was used to estimate the incident rate ratio (IRR) of neuropathological outcomes. Diabetes was associated with total dementia (RR 1.5 [95% CI 1.01-2.2]), Alzheimer's disease (AD; 1.8 [1.1-2.9]), and vascular dementia (VsD; 2.3 [1.1-5.0]). Individuals with both type 2 diabetes and the APOE epsilon4 allele had an RR of 5.5 (CI 2.2-13.7) for AD compared with those with neither risk factor. Participants with type 2 diabetes and the epsilon4 allele had a higher number of hippocampal neuritic plaques (IRR 3.0 [CI 1.2-7.3]) and neurofibrillary tangles in the cortex (IRR 3.5 [1.6-7.5]) and hippocampus (IRR 2.5 [1.5-3.7]), and they had a higher risk of cerebral amyloid angiopathy (RR 6.6, 1.5-29.6). Type 2 diabetes is a risk factor for AD and VsD. The association between diabetes and AD is particularly strong among carriers of the APOE epsilon4 allele. The neuropathological data are consistent with the clinical results.     

Weight-loss intention in the well-functioning, community-dwelling elderly: associations with diet quality, physical activity, and weight change

BACKGROUND: Many older adults desire to lose weight, yet the proportion with a health-related weight-loss indication, weight-loss strategies, and success is unknown. OBJECTIVE: We examined the associations of reported intention to lose weight with health-related indications for weight loss, diet quality, physical activity, and weight-loss success in well-functioning older adults. DESIGN: This prospective, community-based cohort included 2708 elderly persons aged 70-79 y at baseline. We determined indication for weight loss by using the modified National Institutes of Health guidelines, diet quality by using the Healthy Eating Index, and weight-loss intention and physical activity by using questionnaires. Measured weight change over 1 y was assessed. RESULTS: Twenty-seven percent of participants reported an intention to lose weight, and 67% of those participants had an indication for weight loss. Participants who reported a weight-loss intention were heavier than those who did not, had more depressive symptoms, and were more likely to be dissatisfied with their weight, regardless of weight-loss indication. Participants with an intention to lose weight reported better eating behaviors and a more active lifestyle than did participants without a weight-loss intention, independent of other health conditions. No significant difference in actual weight loss was found between participants intending and not intending to lose weight, regardless of indication for weight loss. CONCLUSIONS: Despite being associated with healthier behaviors, the intention to lose weight did not predict greater weight loss in this well-functioning elderly cohort. More attention needs to be focused on the necessity and efficacy of specific strategies for weight loss in older adults.