Lifestyle, CVD Risk and Cognitive Impairment

描述（由申请人提供）：心血管疾病（CVD）是美国死亡和残疾的主要原因，影响超过8100万美国成年人。众所周知，高血压、糖尿病和高脂血症等危险因素不仅使个体有患心血管疾病的风险，而且还使他们有患神经认知障碍和痴呆的风险。心血管疾病危险因素已被证明与一系列神经生理和神经解剖学变化（例如，大脑皮层下区域小动脉狭窄、脑血流量减少、血脑屏障破坏）相关，从而导致认知障碍和痴呆。具有心血管疾病危险因素的患者表现出无痴呆的认知障碍（CIND），被认为处于正常衰老和早期痴呆之间的过渡阶段。人们对CIND非常感兴趣，因为纵向研究已经证明，这些人非常容易患上痴呆症。运动和饮食已被证明可以改善心血管疾病的风险因素，而且在预防痴呆症方面，生活方式也显得特别有希望。在这项应用中，我们提出了一项随机临床试验，针对具有心血管疾病危险因素的患者，这些患者也具有主观认知抱怨和客观证据的神经认知缺陷无痴呆（CIND）。提出了一个2 × 2设计来检查饮食和运动对神经认知的独立和联合影响。参与者将被随机分配到6个月的有氧运动，使用DASH饮食调整饮食，或运动和饮食相结合；第四组（对照组）将接受健康教育，但除此之外将保持他们通常的饮食和活动习惯。该研究旨在(a)评估有氧运动和DASH饮食在改善CVD危险因素和CIND患者神经认知功能方面的有效性；(b)研究运动和饮食改善神经认知的可能机制；(c)考虑潜在的治疗调节因子，包括亚临床CVD。这些数据将具有重要的临床意义，确定生活方式在多大程度上可以改善神经认知衰退易感患者的神经认知，并将确定可能解释CIND患者神经认知改善的关键血管和相关生物标志物。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is the leading cause of death and disability in the United States, affecting more than 81 million American adults. It is well established that risk factors such as hypertension, diabetes, and hyperlipidemia not only place individuals at risk for CVD, but also place them at risk for neurocognitive impairment and dementia. CVD risk factors have been shown to be associated with a cascade of neurophysiologic and neuroanatomic changes (e.g., narrowing of the small arteries in the subcortical regions of the brain, reduced cerebral blood flow, disruption of the blood-brain barrier), resulting in cognitive impairment and dementia. Patients with CVD risk factors who exhibit cognitive impairment without dementia (CIND) are considered to be in a transition stage between normal aging and early dementia. There is great interest in CIND because longitudinal studies have documented that such individuals are highly vulnerable to developing dementia. Exercise and diet have been shown to improve CVD risk factors and also appear particularly promising lifestyle approaches for preventing dementia. In this application, we propose a randomized clinical trial of patients with CVD risk factors who also are characterized by subjective cognitive complaints and objective evidence of neurocognitive deficits without dementia (CIND). A 2 by 2 design is proposed to examine the independent and combined effects of diet and exercise on neurocognition. Participants will be randomly assigned to 6 months of aerobic exercise, dietary modification using the DASH diet, or a combination of both exercise and diet; a fourth (control) group will receive health education but otherwise will maintain their usual dietary and activity habits. The study will aim to (a) evaluate the effectiveness of aerobic exercise and the DASH diet in improving neurocognitive functioning in patients with CVD risk factors and CIND; (b) examine possible mechanisms by which exercise and diet improve neurocognition; and (c) consider potential moderators of treatment, including subclinical CVD. These data will have important clinical significance by determining the extent to which lifestyle may improve neurocognition in patients vulnerable to neurocognitive decline and will identify key vascular and related biomarkers that may account for improved neurocognition among persons with CIND.