Venturelli Massimo, Pedrinolla Anna, Boscolo Galazzo Ilaria, Fonte Cristina, Smania Nicola, Tamburin Stefano, Muti Ettore, Crispoltoni Lucia, Stabile Annamaria, Pistilli Alessandra, Rende Mario, Pizzini Francesca B, Schena Federico
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Department of Medicine, University of Verona, Verona, Italy.
Front Physiol. 2018 Mar 14;9:169. doi: 10.3389/fphys.2018.00169. eCollection 2018.
Advanced aging, vascular dysfunction, and nitric oxide (NO) bioavailability are recognized risk factors for Alzheimer's disease (AD). However, the contribution of AD, , to this putative pathophysiological mechanism is still unclear. To better answer this point, we quantified cortical perfusion with arterial spin labeling (PVC-CBF), measured ultrasound internal carotid (ICA), and femoral (FA) artery blood flow in a group of patients with similar age (~78 years) but different cognitive impairment (i.e., mild cognitive impairment MCI, mild AD-AD1, moderate AD-AD2, and severe AD-AD3) and compared them to young and healthy old (aged-matched) controls. NO-metabolites and passive leg-movement (PLM) induced hyperemia were used to assess systemic vascular function. Ninety-eight individuals were recruited for this study. PVC-CBF, ICA, and FA blood flow were markedly (range of 9-17%) and significantly (all < 0.05) reduced across the spectrum from YG to OLD, MCI, AD1, AD2, AD3 subjects. Similarly, plasma level of nitrates and the values of PLM were significantly reduced (range of 8-26%; < 0.05) among the six groups. Significant correlations were retrieved between plasma nitrates, PLM and PVC-CBF, CA, and FA blood flow. This integrative and comprehensive approach to vascular changes in aging and AD showed progressive changes in NO bioavailability and cortical, extracranial, and peripheral circulation in patients with AD and suggested that they are directly associated with AD and not to aging. Moreover, these results suggest that AD-related impairments of circulation are progressive and not confined to the brain. The link between cardiovascular and the central nervous systems degenerative processes in patients at different severity of AD is likely related to the depletion of NO.
衰老、血管功能障碍和一氧化氮（NO）生物利用度是公认的阿尔茨海默病（AD）风险因素。然而，AD对这种假定病理生理机制的作用仍不清楚。为了更好地回答这一问题，我们采用动脉自旋标记（PVC-CBF）定量大脑皮质灌注，测量一组年龄相近（约78岁）但认知障碍程度不同（即轻度认知障碍MCI、轻度AD-AD1、中度AD-AD2和重度AD-AD3）患者的颈内动脉（ICA）和股动脉（FA）血流，并将其与年轻健康的老年（年龄匹配）对照组进行比较。使用NO代谢物和被动腿部运动（PLM）诱导的充血来评估全身血管功能。本研究招募了98名个体。从YG到OLD、MCI、AD1、AD2、AD3受试者，PVC-CBF、ICA和FA血流显著（9%-17%）且明显（均P<0.05）降低。同样，六组中血浆硝酸盐水平和PLM值也显著降低（8%-26%；P<0.05）。血浆硝酸盐、PLM与PVC-CBF、CA和FA血流之间存在显著相关性。这种针对衰老和AD血管变化的综合方法显示，AD患者的NO生物利用度以及皮质、颅外和外周循环存在渐进性变化，表明它们与AD直接相关，而非衰老。此外，这些结果表明，AD相关的循环障碍是渐进性的，并不局限于大脑。不同严重程度AD患者心血管和中枢神经系统退行性过程之间的联系可能与NO耗竭有关。
