治疗的主要目标是通过对有卒中或 TIA 病史的人群进行主要危险因素的最佳控制,防止进一步的脑血管病发生。
预防措施局灶性脑损伤可能的病因以及血管性病变类型和位置的影响。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com 这包括动脉粥样硬化缺血性疾病和心源性疾病患者。 动脉粥样硬化疾病是指出现脑栓塞和疑似动脉到动脉栓塞而无明确的心源性因素的疾病。 心源性栓塞性疾病是指出现脑栓塞且有明确的心源性因素(例如心房颤动、瓣膜性心脏病、左心室血栓)的疾病。
脑血管病的预防
仍然没有良好的证据证明阿司匹林在治疗血管性痴呆患者方面的有效性。[25]Rands G, Orrell M. Aspirin for vascular dementia. Cochrane Database Syst Rev. 2000;(4):CD001296.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001296/fullhttp://www.ncbi.nlm.nih.gov/pubmed/10796639?tool=bestpractice.com 然而,作为对脑血管病的二级预防,它仍然有用。
预防脑血管病的主要选择包括:抗血小板疗法治疗动脉粥样硬化性疾病、抗凝疗法治疗心源性栓塞性疾病,以及颈动脉内膜切除术或颈动脉血管成形与支架置入术治疗颈动脉狭窄。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com
有证据支持使用阿司匹林、氯吡格雷或阿司匹林/双嘧达莫联合治疗,以防止与动脉粥样硬化或小血管病变有关的卒中或 TIA 患者的进一步发生脑梗死。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com[26]Hankey GJ. Clinical update: Management of stroke. Lancet. 2007;369:1330-1332.http://www.ncbi.nlm.nih.gov/pubmed/17448805?tool=bestpractice.com 阿司匹林单药治疗或阿司匹林/双嘧达莫联合治疗是此类患者的初始治疗。氯吡格雷是卒中二级预防和阿司匹林过敏患者的合理治疗选择。抗血小板药物的选择应遵循个体化原则,根据患者危险因素情况、费用、耐受性、药物的相对已知疗效以及其他临床特征确定。可以考虑在轻度缺血性卒中或 TIA 发作后 24 小时内开始阿司匹林和氯吡格雷联合治疗,持续 21 天。在轻度卒中或 TIA 发作后的数天至数年内开始阿司匹林加氯吡格雷联合治疗并持续 2-3 年,与单独使用两种药物中的任一种相比,出血风险会增加,因此不建议将该疗法用于缺血性卒中或 TIA 后的常规长期二级预防。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com
有证据表明阿司匹林/双嘧达莫联合服用与单用阿司匹林相比,绝对卒中危险可降低 3%(16% 比 13%)[27]Halkes PH, van Gijn J, Kappelle LJ, et al. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20;367(9523):1665-73.http://www.ncbi.nlm.nih.gov/pubmed/16714187?tool=bestpractice.com 与阿司匹林相比,氯吡格雷使绝对卒中风险降低 0.5%。[28]Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and asprin vs asprin alone for the protection of atherothrombotic events. N Engl J Med. 2006;354:1706-1717.http://www.ncbi.nlm.nih.gov/pubmed/16531616?tool=bestpractice.com 颈动脉内膜剥脱术是治疗症状性颈动脉狭窄(等级 >70%)的首选方法。 对于有症状、存在血管内介入相关并发症平均/较低风险的患者,当颈内动脉管腔直径通过无创成像显示减小>70%,或通过基于导管的成像或伴佐证的无创成像显示减小>50%,且预期围手术期卒中率或死亡率<6% 时,颈动脉血管成形与支架置入术可作为颈动脉内膜切除术的替代疗法。 对于老年患者(即 70 岁以上),和颈动脉血管成形与支架置入术相比,颈动脉内膜切除术可能带来结局的改善,特别是当动脉解剖结构不利于血管内介入治疗时。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com心血管事件的减少:高质量证据表明,颈动脉内膜剥脱术对预防有症状狭窄和狭窄≥70%而无闭塞人群的卒中进展是非常有益的。[29]Brott TG, Brown RD, Meyer FB, et al. Carotid revascularization for prevention of stroke: carotid endarterectomy and carotid artery stenting. Mayo Clin Proc. 2004 Sep;79(9):1197-208.http://www.ncbi.nlm.nih.gov/pubmed/15357045?tool=bestpractice.com[30]Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med. 1998 Nov 12;339(20):1415-25.http://www.nejm.org/doi/full/10.1056/NEJM199811123392002http://www.ncbi.nlm.nih.gov/pubmed/9811916?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。 华法林可高效降低存在于心房颤动的心源性卒中危险。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com 新型抗凝制剂阿哌沙班、达比加群与利伐沙班也能有效降低非心脏瓣膜性心房颤动患者的心源性卒中危险。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com
还应积极改变危险因素以降低卒中危险,包括体育活动、饮食调整、降低胆固醇、血压控制和糖尿病/血糖控制。 能够进行锻炼的患者应每周多天应进行 40 分钟中等至高强度的运动。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com 应建议吸烟者停止吸烟。 应建议酒精摄入量大的人减少或停止摄入。
这些治疗方法的主要问题是对健康生活方式的顺应性和药物治疗不良反应。 抗血小板和抗凝剂与出血危险有关联,他汀类药物与肌病和肝功能异常有关联。
改善认知症状或防止脑血管病相关痴呆的治疗
胆碱酯酶抑制剂和美金刚已在血管性痴呆患者身上进行过试验。 然而,它们不是特别有效,并且由于界定纯血管性痴呆有困难,使得试验难以设计。 这些药物的效果很小,对单独血管病因痴呆患者的临床益处不确切。[31]Demaerschalk BM, Wingerchuk DM. Treatment of vascular dementia and vascular cognitive impairment. Neurologist. 2007;13:37-41.http://www.ncbi.nlm.nih.gov/pubmed/17215726?tool=bestpractice.com[32]Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol. 2007;6:782-792.http://www.ncbi.nlm.nih.gov/pubmed/17689146?tool=bestpractice.com[33]Korczyn AD. Drugs for vascular dementia. Lancet Neurol. 2007;6:749-751.http://www.ncbi.nlm.nih.gov/pubmed/17706553?tool=bestpractice.com[34]Black SE. Therapeutic issues in vascular dementia: studies, designs and approaches. Can J Neurol Sci. 2007;34(suppl 1):S125-S130.http://www.ncbi.nlm.nih.gov/pubmed/17474183?tool=bestpractice.com[35]Wilkinson D, Róman G, Salloway S, et al. The long-term efficacy and tolerability of donepezil in patients with vascular dementia. Int J Geriatr Psychiatry. 2010;25:305-313.http://www.ncbi.nlm.nih.gov/pubmed/19623601?tool=bestpractice.com治疗:有来自系统评价的高质量证据表明,针对血管性痴呆,几乎不存任何特异性治疗能够获益的相关证据。[33]Korczyn AD. Drugs for vascular dementia. Lancet Neurol. 2007;6:749-751.http://www.ncbi.nlm.nih.gov/pubmed/17706553?tool=bestpractice.com[34]Black SE. Therapeutic issues in vascular dementia: studies, designs and approaches. Can J Neurol Sci. 2007;34(suppl 1):S125-S130.http://www.ncbi.nlm.nih.gov/pubmed/17474183?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。
然而,应确保患者未合并需要接受这种治疗的阿尔茨海默痴呆,因为胆碱酯酶抑制剂对这些患者有一定的益处。[36]Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006;(1):CD005593.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005593/fullhttp://www.ncbi.nlm.nih.gov/pubmed/16437532?tool=bestpractice.com认知功能的改善:低质量研究证据表明,与安慰剂对照相比,使用6个月的乙酰胆碱酯酶抑制剂可以稍微改善血管性痴呆患者后的认知功能,但不能改善患者的总体功能得分以及日常行为能力得分。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。 阿尔茨海默病和血管性痴呆共存的混合性痴呆被认为见于高达 50% 的痴呆病例。[37]Holmes C, Cairns N, Lantos P, et al. Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies. Br J Psychiatry. 1999; 174:45-50.http://www.ncbi.nlm.nih.gov/pubmed/10211150?tool=bestpractice.com
已有用抗高血压药物治疗或预防痴呆或认知衰退的几项试验。 2 项试验的结果提示血管紧张素转换酶 (ACE) 抑制剂(即:PROGRESS 研究中的培哚普利)和钙通道阻滞剂(即:SYST-EUR 研究中的尼群地平)有预防阿尔茨海默痴呆和卒中相关痴呆的效果。[38]Hanon O, Forette F. Prevention of dementia: lessons from SYST-EUR and PROGRESS. J Neurol Sci. 2004;226:71-74.http://www.ncbi.nlm.nih.gov/pubmed/15537524?tool=bestpractice.com 系统评价发现使用尼莫地平(另一种钙通道阻滞剂)具有一定疗效,使用血管紧张素转换酶抑制剂和利尿剂也是如此。[39]López Arrieta J, Birks J. Nimodipine for primary degenerative, mixed and vascular dementia. Cochrane Database Syst Rev. 2002;(3):CD000147.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000147/fullhttp://www.ncbi.nlm.nih.gov/pubmed/12137606?tool=bestpractice.com[40]Shah K, Qureshi SU, Johnson M, et al. Does use of antihypertensive drugs affect the incidence or progression of dementia? A systematic review. Am J Geriatr Pharmacother. 2009;7:250-261.http://www.ncbi.nlm.nih.gov/pubmed/19948301?tool=bestpractice.com [
]Is there randomized controlled trial evidence to support the use of nimodipine in people with primary degenerative, mixed and vascular dementia?https://cochranelibrary.com/cca/doi/10.1002/cca.194/full显示答案 然而,其他几项大型试验的结果表明,血压降低并不能预防认知减退。[41]McGuinness B, Todd S, Passmore P, et al. Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev. 2009;(4):CD004034.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004034.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19821318?tool=bestpractice.com预防认知衰退:有来自系统评价的高质量证据表明,既往无脑血管病的患者中,没有任何证据支持使用降压药物可以预防认知减退。[41]McGuinness B, Todd S, Passmore P, et al. Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev. 2009;(4):CD004034.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004034.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19821318?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。 已证实降压治疗对预防脑血管病的作用,因此应用于此目的,其间接作用之一可能为预防与卒中相关的认知衰退。
研究发现,使用他汀类药物对改善认知功能没有明显益处。[42]Etminan M, Gill S, Sammii A. The role of lipid-lowering drugs in cognitive function: a meta-analysis of observational studies. Pharmacotherapy. 2003;23:726-730.http://www.ncbi.nlm.nih.gov/pubmed/12820814?tool=bestpractice.com[43]Bernick C, Katz R, Smith NL, et al. Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology. 2005;65:1388-1394.http://www.ncbi.nlm.nih.gov/pubmed/16275825?tool=bestpractice.com认知功能的改善来自观察性研究的低质量证据表明,他汀类药物对于改善高龄患者(包括血管性痴呆患者)的认知功能无明显效果。[42]Etminan M, Gill S, Sammii A. The role of lipid-lowering drugs in cognitive function: a meta-analysis of observational studies. Pharmacotherapy. 2003;23:726-730.http://www.ncbi.nlm.nih.gov/pubmed/12820814?tool=bestpractice.com[43]Bernick C, Katz R, Smith NL, et al. Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology. 2005;65:1388-1394.http://www.ncbi.nlm.nih.gov/pubmed/16275825?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。 研究显示,他汀类药物治疗并不能预防有血管疾病风险患者的认知减退或痴呆。[44]McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2016;(1):CD003160.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003160.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26727124?tool=bestpractice.com 他汀类药物治疗血管性痴呆的主要作用是防止进一步的缺血事件发生。[24]Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.http://stroke.ahajournals.org/content/45/7/2160.longhttp://www.ncbi.nlm.nih.gov/pubmed/24788967?tool=bestpractice.com[45]Amarenco P, Bogousslavsky J, Callahan A 3rd, et al; The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. 2006 Aug 10;355(6):549-59.http://www.nejm.org/doi/full/10.1056/NEJMoa061894#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/16899775?tool=bestpractice.com心血管事件的减少:来自大型随机对照试验的高质量的证据表明,与安慰剂对照或者未接受治疗的患者相比,使用他汀类药物降低胆固醇可有效降低心血管病高危人群的卒中风险。[45]Amarenco P, Bogousslavsky J, Callahan A 3rd, et al; The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. 2006 Aug 10;355(6):549-59.http://www.nejm.org/doi/full/10.1056/NEJMoa061894#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/16899775?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。
目前,针对强化老年人糖尿病控制以预防认知衰退的研究正在进行中。
经常进行体育活动可能有助于预防血管性痴呆。[46]Aarsland D, Sardahaee FS, Anderssen S, et al. Is physical activity a potential preventive factor for vascular dementia? A systematic review. Aging Ment Health. 2010;14:386-395.http://www.ncbi.nlm.nih.gov/pubmed/20455113?tool=bestpractice.com
我们已确定在预防脑白质病变进展方面没有已发表的试验。