Increase in Blood Pressure: Effects on Cognition, Mood and Life Quality in SCI

血压升高：对 SCI 患者认知、情绪和生活质量的影响

• 批准号: 9416834
• 负责人: Jill M. Wecht
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9416834
• 关键词: Acute; Address; Adrenergic Agents; Adrenergic alpha-Agonists; Adverse event; Age; Antihypertensive Agents; Anxiety; Attention; Autonomic Dysreflexia; Belief; Blood Flow Velocity; Blood Pressure; Cardiovascular system; Cerebrovascular Circulation; Cervical; Chronic; Clinical; Clinical Management; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Data; Digit structure; Disease; Double-Blind Method; Emotional; Etiology; Face; Fatigue; Head; Health; Hour; Hypertension; Hypotension; Impaired cognition; Incidence; Individual; Intervention; Laboratories; Lesion; Limb structure; Literature; Longitudinal Studies; Medical; Memory; Memory impairment; Mental Depression; Midodrine; Moods; Nature; Orthostasis; Orthostatic Hypotension; Outpatients; Paper; Perception; Persons; Pilot Projects; Placebo Control; Placebos; Population; Prevalence; Psyche structure; Quality of life; Randomized; Reaction Time; Reporting; Rest; Risk; Sampling; Secondary to; Severities; Speed; Spinal cord injury; Systemic blood pressure; Test Result; Veterans; Work; base; cerebrovascular; cognitive function; cognitive performance; cognitive testing; cohort; experience; falls; hypertension treatment; improved; middle cerebral artery; mortality; normotensive; performance tests; processing speed; public health relevance; response; social

In 1927, Norris described individuals with low blood pressure (BP) as persons who lacked stamina, tired easily, complained of cold extremities and showed an inability to do prolonged mental or physical work; he was quoted as saying; "they are not exactly ill; yet they are rarely well." 1 However, several more recent papers have challenged the notion that low BP is a health concern, and even suggest that hypotension is the ideal "normal" BP.2, 3 Individuals with spinal cord injury (SCI) above T5 are reported to struggle with chronic hypotension,4-11 episodic orthostatic hypotension (OH) 12-16 and post-prandial hypotension.17 In fact, we recently reported that, over the course of a typical 24-hour day, the incidence of hypotension was as high as 70% in those with cervical lesions.18 In addition our unpublished data suggest that the incidence of hypotension is 2.5 fold increased in veterans with SCI compared to age-matched veterans without SCI. However, chronic hypotension is often not clinically addressed because the vast majority of hypotensive individuals remain asymptomatic. That said there evidence in the general medical literature supporting associations between asymptomatic hypotension, cognitive deficits, adverse changes in mood and quality of life (QOL). Compared to normotensive age-matched controls, otherwise healthy subjects with chronic asymptomatic hypotension are reported to have slowed cognitive speed, 19 fewer word recall, 20 decreased accuracy of response,21 limited attention,20 prolonged reaction times,19, 21, 22 and reduced memory and concentration capacity. 21, 22 In addition, several papers have reported findings suggesting significant associations between chronic hypotension and increased incidence of depression,23-30 anxiety,25, 26 unexplained tiredness,24, 31 and poor perception of well being.32 Although many hypotensive individuals with chronic SCI remain asymptomatic and do not raise clinical suspicion warranting intervention, we believe, and have demonstrated that asymptomatic chronic hypotension has adverse cognitive consequences.33-35 It must be appreciated that the superimposition of cognitive impairment on the physical, social and emotional limitations already experienced by many individuals with SCI may severely impact autonomy and social independence thereby diminishing QOL.36, 37 There is compelling evidence in the general medical literature suggesting that elevation in systemic BP, following midodrine hydrochloride administration, increases resting cerebral blood flow (CBF) and improves CBF responses to cognitive testing resulting in better test performance in healthy individuals with chronic hypotension. 38, 39 Because it is believed that the etiology of hypotension in the SCI population is the result of adrenergic insufficiency, midodrine, an alpha-adrenergic agonist, is considered a first line treatment, 40-42 and we have demonstrated significant increases in systemic BP in hypotensive individuals with SCI.43, 44 However, in general, data describing the BP effect of midodrine have been collected in small samples of hypotensive subjects with SCI during laboratory observations,44, 45 the benefit of sustained elevation in systemic BP on CBF, cognitive function, mood and QOL has not been rigorously studied in the SCI population. Data generated in this pilot project will be used to power a large-scale clinical trial to determine the clinical benefit of sustained increases in BP on CBF, cognitive function, mood and QOL in persons with SCI.

1927年，诺里斯将患有低血压的人描述为缺乏耐力、疲倦的人 很容易，抱怨四肢发冷，表现出无法做长时间的脑力或体力工作； 有人引用他的话说：“他们并不是真的病了，但他们很少会好起来的。” 论文对低血压是一个健康问题的观点提出了质疑，甚至认为低血压是 理想的“正常”BP.2，据报道，3名脊髓损伤(SCI)在T5以上的人正在与 慢性低血压，4-11次发作的直立性低血压(OH)12-16和餐后低血压。 事实上，我们最近报道，在典型的24小时一天中，低血压的发生率是 在有宫颈病变的人中高达70%。18此外，我们未发表的数据表明， 患有脊髓损伤的退伍军人低血压发生率是同龄退伍军人的2.5倍 没有SCI。然而，慢性低血压通常没有在临床上得到解决，因为绝大多数 低血压者仍无症状。也就是说，在普通医学文献中有证据表明 支持无症状性低血压、认知缺陷、情绪不良变化之间的关联 和生活质量(QOL)。与血压正常的年龄匹配的对照组相比，其他健康的受试者 据报道，慢性无症状低血压减慢了认知速度，减少了19个单词的回忆， 20个反应的准确性下降，21个注意力受限，20个反应时间延长，19，21，22 记忆力和专注力。21，22此外，几篇论文报道了一些发现 慢性低血压与抑郁症发病率增加的显著关联，23-30 焦虑，25岁，26岁原因不明的疲倦，24岁，31岁，感觉良好。32尽管许多人患有低血压 慢性脊髓损伤患者仍无症状，不会引起临床怀疑 我们认为，干预措施已经证明，无症状的慢性低血压具有不良影响。 认知后果。33-35必须认识到，认知障碍叠加在 许多脊髓损伤患者已经经历了身体、社交和情感方面的限制，这可能 严重影响自治和社会独立，从而削弱QOL36，37令人信服 一般医学文献中的证据表明，米多君后全身血压升高 增加静息脑血流量(CBF)并改善CBF反应 认知测试使患有慢性低血压的健康个体的测试表现更好。38、39 因为人们认为脊髓损伤人群中低血压的病因是肾上腺素能 米多君，一种α-肾上腺素能激动剂，被认为是一线治疗，40-42，我们有 在患有SCI.43，44的低血压病患者中，全身血压显著升高 一般说来，描述米多君血压效应的数据是在小样本的低血压患者中收集的。 在实验室观察期间患有脊髓损伤的受试者，44，45全身血压持续升高的益处 在脊髓损伤人群中，CBF、认知功能、情绪和生活质量还没有得到严格的研究。数据 在这个试点项目中产生的数据将被用于推动一项大规模的临床试验，以确定 血压持续升高对人的脑血流、认知功能、情绪和生活质量的临床益处 和SCI一起。

项目成果

Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI.

双盲、安慰剂对照交叉试验，以确定米多君对 SCI 患者认知测试期间血压的影响。

• DOI: 10.1038/s41393-020-0448-0
• 发表时间: 2020
• 期刊: Spinal cord
• 影响因子: 2.2
• 作者: Wecht,JillM;Weir,JosephP;Katzelnick,CaitlynG;Chiaravalloti,NancyD;Kirshblum,StevenC;Dyson-Hudson,TrevorA;Weber,Erica;Bauman,WilliamA
• 通讯作者: Bauman,WilliamA