Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
J Alzheimers Dis. 2021;79(3):1285-1296. doi: 10.3233/JAD-200754.
Coronary artery disease (CAD) increases risk for vascular cognitive impairment-no dementia (VCIND), a precursor to dementia, potentially through persistent oxidative stress.
This study assessed peripheral glutathione peroxidase activity (GPX), which is protective against oxidative stress, in VCIND versus cognitively normal CAD controls (CN). GPX activity was also evaluated as a biomarker of cognition, particularly verbal memory.
120 CAD patients with VCIND (1SD below norms on executive function or verbal memory (VM)) or without (CN) participated in exercise rehabilitation for 24 weeks. Neurocognitive and cardiopulmonary fitness (VO2peak) assessments and plasma were collected at baseline and 24-weeks.
GPX was higher in VCIND compared to CN (F1,119 = 3.996, p = 0.048). Higher GPX was associated with poorer baseline VM (β= -0.182, p = 0.048), and longitudinally with VM decline controlling for sex, body mass index, VO2peak, and education (b[SE] = -0.02[0.01], p = 0.004). Only CN participants showed improved VM performance with increased fitness (b[SE] = 1.30[0.15], p < 0.005).
GPX was elevated in VCIND consistent with a compensatory response to persistent oxidative stress. Increased GPX predicted poorer cognitive outcomes (verbal memory) in VCIND patients despite improved fitness.
冠心病(CAD)增加了血管性认知障碍但非痴呆(VCIND)的风险,这是痴呆的前兆,可能是通过持续的氧化应激。
本研究评估了外周谷胱甘肽过氧化物酶活性(GPX),其对氧化应激具有保护作用,在 VCIND 与认知正常的 CAD 对照(CN)中进行评估。还评估了 GPX 活性作为认知的生物标志物,特别是言语记忆。
120 名 CAD 患者患有 VCIND(执行功能或言语记忆(VM)低于正常 1 个标准差)或无 VCIND(CN),参加了 24 周的运动康复。在基线和 24 周时采集神经认知和心肺健康(VO2peak)评估和血浆。
与 CN 相比,VCIND 中的 GPX 更高(F1,119=3.996,p=0.048)。较高的 GPX 与基线 VM 较差相关(β=-0.182,p=0.048),并且在控制性别、体重指数、VO2peak 和教育的情况下,与 VM 下降相关联(b[SE]=-0.02[0.01],p=0.004)。只有 CN 参与者随着健康状况的改善,VM 表现得到了改善(b[SE]=1.30[0.15],p<0.005)。
VCIND 中的 GPX 升高与持续氧化应激的代偿反应一致。尽管健康状况有所改善,但增加的 GPX 预测 VCIND 患者的认知结果(言语记忆)较差。