Vascular risk factors and Alzheimer's disease

Vascular cognitive impairment risk factors include stroke, hypertension, diabetes and atherosclerosis. In the elderly, vascular risk factors occur in the presence of high levels of amyloid in the aging brain. Stroke alters the clinical expression of a given load of Alzheimer's disease (AD) pathology. Experimentally, large vessel infarcts or small striatal infarcts are larger in the presence of amyloid. Patients with minor cerebral infarcts and moderate AD lesions will develop the clinical manifestations of dementia. Moreover, there is also an association between other vascular risk factors and the clinical expression of cognitive decline and dementia. The risk of AD is increased in subjects with adult-onset diabetes mellitus, hypertension, atherosclerotic disease and atrial fibrillation. Experimentally, small striatal infarcts in the presence of high levels of amyloid in the brain exhibit a progression in infarct size over time with enhanced degree of cognitive impairment, AD-type pathology and neuroinflammation compared with striatal infarcts or high amyloid levels alone.     

Vascular risk factors and Alzheimer's disease

OBJECTIVE: We aim to summarise the recent and accumulating epidemiological research which suggests that cardiovascular disease and vascular risk factors play an important role as risk factors for Alzheimer's disease (AD) in later life. METHOD: The epidemiological literature is summarised in considering the evidence for such an association, focusing on optimally designed population-based studies. Potential mechanisms of association are considered, drawing on relevant findings from neuroscience. RESULTS: Cardiovascular disease and vascular risk disorders appear to be important factors in the aetiology of AD. However, there is a paucity of prospective studies with an adequate duration of follow-up to investigate the apparent age- and time-dependent nature of these associations. CONCLUSIONS: Vascular disorders represent potentially preventable risk factors with an important population impact due to their high prevalence in developed countries. The concept of AD and vascular dementia as clearly distinguishable disorders clinically or aetiologically is becoming increasingly tenuous. A better understanding of the relationship between AD and vascular disorders will depend on a more flexible diagnostic and conceptual framework.     

Inflammatory risk factors and pathologies associated with Alzheimer's disease

The importance of inflammatory processes in Alzheimer's disease (AD) progression has been confirmed during the past decade by the intensive investigation of inflammatory mediators in the brain of AD patients as well as by the genetic and drug manipulation of animal models of AD. Imaging studies have revealed that the activation of microglia occurs in early stages of the disease, even before plaque and tangle formation, and is correlated with early cognitive deficits. In this review, we analyze how different risk factors, such as trauma, stroke, infection, and metabolic diseases can lead to an acceleration of the inflammatory response in the AD brain and to an increased risk of developing this disorder. The use of imaging techniques for early detection of glial activation which offer the advantage of investigating how potential anti-inflammatory therapies may influence disease progression and levels of cognition is also discussed.     

Assessing the health of adult daughter former caregivers for elders with Alzheimer's disease

Past research is varied in assessing the effect of caregiving on health, particularly caregivers in the postcaregiving phase. The variation may be due, in part, to methodological issues, including the use of health measures not psychometrically tested. The study examines the Medical Outcomes Study Short Form 36 (SF-36) health survey with 102 former caregivers whose family member was deceased for at least one year at the time of the study and had been identified as having Alzheimer's disease or a related disorder. The SF-36 measures eight dimensions of physical and mental health and has been tested on a variety of populations, though not with former daughter caregivers. Confirmatory Factor Analysis supported the factorial validity of the SF-36 for this population, indicating it is a promising tool for understanding postcaregiver health.     

Military risk factors for Alzheimer's disease

Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are signature injuries of the wars in Iraq and Afghanistan and have been linked to an increased risk of Alzheimer's disease (AD) and other dementias. A meeting hosted by the Alzheimer's Association and the Veterans' Health Research Institute (NCIRE) in May 2012 brought together experts from the U.S. military and academic medical centers around the world to discuss current evidence and hypotheses regarding the pathophysiological mechanisms linking TBI, PTSD, and AD. Studies underway in civilian and military populations were highlighted, along with new research initiatives such as a study to extend the Alzheimer's Disease Neuroimaging Initiative (ADNI) to a population of veterans exposed to TBI and PTSD. Greater collaboration and data sharing among diverse research groups is needed to advance an understanding and appropriate interventions in this continuum of military injuries and neurodegenerative disease in the aging veteran.     

Biochemical markers and risk factors of Alzheimer's disease

As the spectrum of therapeutic options broadens, the possibility of an early and accurate diagnosis of Alzheimer's disease (AD), or even isolation of a group at high risk of subsequent cognitive decline, is focusing widespread attention. Therefore, biological markers or risk factors of AD are highly desirable. In this work, we give an overview of the most extensively studied AD biomarkers, namely beta-amyloid, tau protein, and phosphorylated tau-protein, alone or in combination. Moreover, we describe the role of inflammatory markers (cytokines, acute phase proteins), oxidative stress markers (isoprostanes, 8-hydroxyguanine, 3-nitrotyrosine, plasma antioxidants, redox transition metals), homocysteine and related vitamins, cholesterol and 24S-hydroxycholesterol in the diagnostic process or prediction of AD. We briefly review less popular, though promising markers of AD - markers of apoptosis, neuronal thread protein, acetyl- and butyrylcholinesterase, sulfatide, kallikreins, matrix-degrading metalloproteinases, and novel isoforms of beta-amyloid and tau. Finally, we discuss the clinical applicability of AD-related biological markers.     

Environmental and dietary risk factors in Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects millions in the aging population worldwide and will affect millions more in the next 20 years. Over 90% of all cases are sporadic, with genetics playing a minor role in the etiology of AD. Therefore, it is crucial to investigate the environment and diet as primary risk factors in AD pathology. This review considers epidemiologic case control studies, and in vitro and in vivo research to investigate the potential of environmental exposure to metals, air pollution and pesticides as well as diet as risk factors for AD. In some cases, the role of genetic mutations and environmental risk is discussed. The evidence examined in this review provides a brief overview of the current literature on selected, significant risk factors in promoting amyloid-beta accumulation and aggregation, thus contributing to neurodegeneration.     

暴力精神分裂症照料者的心理健康及影响因素分析

目的 探索暴力精神分裂症照料者的心理健康及影响因素。方法 连续纳入2014年1 月至 2016 年12 月在重庆市精神卫生中心就诊的暴力精神分裂症患者照料者487 人（暴力精神分裂症组），另 选取与暴力精神分裂症患者性别、年龄、受教育程度、病程相匹配的无暴力行为精神分裂症患者的照料 者479 例（非暴力精神分裂症组）作为对照组，采用症状自评量表90 项症状清单（SCL-90）及社会支持评 定量表（SSRS）进行评估。结果 暴力精神分裂症组照料者在SCL-90 量表中总分［（176.23±54.59）分比 （167.26±63.06）分］、躯体化［（22.72±7.25）分比（21.46±8.74）分］、强迫［（20.67±6.36）分比（19.65±6.93）分］、 人际关系敏感［（18.18±6.51）分比（17.25±6.56）分］、抑郁［（25.79±9.08）分比（24.45±9.68）分］、焦虑 ［（18.89±6.72）分比（17.96±7.16）分］、敌对［（11.22±4.93）分比（10.40±4.68）分］、恐怖［（13.05±5.62）分比 （12.28±5.76）分］、偏执［（11.97±4.54）分比（11.27±5.06）分］、精神病性［（19.91±7.20）分比（18.96±7.86）分］ 和其他［（14.25±6.16）分比（13.38±5.54）分］10个因子分及SSRS中客观支持［（6.11±1.84）分比（5.85±2.11）分］、 主观支持［（15.39±3.75）分比（14.85±3.75）分］、支持利用［（6.63±1.97）分比（5.92±2.12）分］得分均高 于非暴力精神分裂症组照料者，且差异均有统计学意义（均P＜ 0.05）。多元逐步回归分析结果显示，病 程、主观支持对照料者的心理健康有影响（F=14.567，P ＜ 0.01）。结论 暴力精神分裂症患者照料者较 不伴有暴力行为精神分裂症患者的照料者心身健康水平均明显低下，其差异受病程及主观支持两因素 影响。     

Early-life risk factors and the development of Alzheimer's disease

OBJECTIVE: To investigate the association of early-life factors with AD. BACKGROUND: The early-life environment and its effect on growth and maturation of children and adolescents are linked to many adult chronic diseases (heart disease, stroke, hypertension, and diabetes mellitus), and these effects are also linked to maternal reproduction. AD may have an early-life link. The areas of the brain that show the earliest signs of AD are the same areas of the brain that take the longest to mature during childhood and adolescence. A poor-quality childhood or adolescent environment could prevent the brain from reaching complete levels of maturation. Lower levels of brain maturation may put people at higher risk for AD. METHODS: In a community-based case-control study (393 cases, 377 controls), we investigated the association of early-life factors and AD. Early-life variables include mother's age at patient's birth, birth order, number of siblings, and area of residence before age 18 years. Patient education level and apolipoprotein E (APOE) genotypes were also included in the analysis. Results: Area of residence before age 18 years and number of siblings are associated with subsequent development of AD. For each additional child in the family the risk of AD increases by 8% (OR = 1.08, 95% CI = 1.01 to 1.15). More controls compared with cases grew up in the suburbs (OR = 0.45, 95% CI = 0.25 to 0.82). APOE epsilon 4 and the patient's education level did not confound or modify the associations. CONCLUSIONS: The early-life childhood and adolescent environment is associated with the risk of AD.     

Consent in Alzheimer's disease research: risk/benefit factors

In the era of chronic disease, we are challenged to find therapies that provide symptomatic relief and ideally, alter the course of the underlying disease. In Alzheimer's disease (AD), these issues are complicated by the disease itself, which affects the subject's decision-making capacity for participation in the research. According to established ethical guidelines it is clear that individuals with impaired capacity may participate in research and their risk should be no greater than that which the individual would have in day to day activities with anticipation of benefits within that realm. Decision making processes are complex and involve proxies who themselves have biases about their loved one and the potential for participating in the research. Newer disease-modifying approaches such as immunotherapy have potential for affecting the course of the underlying disease but with greater risk of more significant side effects. Ideally the health care of the subjects is not disadvantaged by research participation. At the same time, trials of potentially riskier therapy are relevant in subjects with the disease. Research for subjects with AD must have appropriate safeguards in place to enable effective progress in innovative therapy for a vulnerable, often elderly population. Recommendations are made which could further our capacity to undertake ethical research in the AD population.     

Lipids and adipokines as risk factors for Alzheimer's disease

To determine if measures of adipokines and other blood lipids differentiate between normal controls and persons with Alzheimer's disease (AD), we examined levels of leptin, adiponectin, total cholesterol, high density lipoproteins (HDL), calculated low density lipoproteins (LDL), triglycerides and apolipoprotein E allele status in 148 early AD subjects and 198 normal controls. We were unable to demonstrate a significant difference between leptin and adiponectin levels between normal controls and AD subjects. We were able to confirm observations of lower HDL and higher total and LDL cholesterol concentration in AD subjects than in controls. As expected, the presence of the apolipoprotein E4 allele distinguished between the two groups.     

Cardiac risk factors and potential treatments in Alzheimer's disease

Dementia is one of the commonest neurological disorders in the elderly population. In regards to the increasing longevity of populations worldwide, prevention of dementia has become a major public health challenge. There has been an intense research in the identification of modifiable risk factors for dementia. These risk factors could then be used as targets for intervention, pharmacologic or non-pharmacologic. Numerous reports of the relation between cardiovascular risk factors and cognitive decline and dementia have been published over the past years. This review focuses on the cardiovascular risk factors hypertension, hyperlipidemia and diabetes mellitus as targets for prevention of cognitive decline, overall dementia and Alzheimer's disease. Observational studies and clinical trials regarding the association between antihypertensive, lipid lowering and antidiabetic medications and the risk of impaired cognition, dementia or Alzheimer's disease are reviewed. Based on these data, we propose that early interventions at reducing these cardiovascular risk factors may have an impact on future incidence and prevalence of cognitive deficits of many etiologies including Alzheimer's disease.     

Marital status and risk of Alzheimer's disease: a French population-based cohort study

OBJECTIVE: To analyze the relationship between marital status and risk of AD or dementia. METHODS: This study was carried out from the Personnes Agées QUID (PAQUID) cohort, an epidemiologic study on normal and pathologic aging after age 65 years. The PAQUID cohort began in 1988. Individuals were followed up at 1, 3, and 5 years, with an active detection of dementia. Marital status was divided into four categories: widowed, never married, divorced or separated, and the reference category, married or cohabitant. The longitudinal relationship between marital status and risk of incident AD or dementia was analyzed by a Cox model with delayed entry. RESULTS: Among the 3,675 individuals initially not demented, 2,106 were married or cohabitants, 1,287 were widowers, 179 were never married, and 103 were divorced or separated. Among the 2,881 individuals reevaluated at least once for the risk of dementia during the 5-year follow-up, 190 incident cases of dementia were identified, including 140 with AD. The relative risks (RRs) of dementia (RR = 1.91, p = 0.018) and of AD (RR = 2.68, p<0.001) were increased for the never-married individuals compared with those who were married or cohabitants. This excess of risk was specifically associated with AD. Adjustment for other risk factors of dementia (education, wine consumption), or for factors reflecting social environment, leisure activities, and depression, did not modify the risk of AD for never-married individuals (RR = 2.31, p = 0.02). CONCLUSIONS: We confirmed an association between marital status and AD, with an excess risk observed among never-married individuals. This association may provide clues about the pathogenesis of AD.