Palmer Jacqueline A, Kaufman Carolyn S, Whitaker-Hilbig Alicen A, Billinger Sandra A
Division of Physical Therapy and Rehabilitation Science, University of Minnesota Medical School, , Minneapolis, MN, United States of America.
Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States of America.
medRxiv. 2024 Oct 13:2024.10.11.24315344. doi: 10.1101/2024.10.11.24315344.
Maintenance of cerebral blood flow during orthostasis is impaired with aging and associated with cognitive decline, but the effect of Apolipoprotein 4-allele () is unknown.
Older adults (n=108) ( carriers, n=47; noncarriers, n=61) diagnosed as cognitively-normal (NC), MCI, or AD participated. Middle cerebral artery blood velocity (MCAv), assessed using Transcranial Doppler ultrasound, and beat-to-beat mean arterial blood pressure (MAP) were continuously recorded during a sit-to-stand transition. Anticipatory and orthostatic-induced MCAv and MAP responses were compared between genotypes and across disease progression.
Cognitively-normal carriers showed greater anticipatory MCAv increase, greater MCAv decrease with orthostasis, and shorter latency of peripheral MAP responses to orthostasis compared to noncarriers. MCAv and MAP responses were delayed and attenuated across the disease progression, with no differences between genotypes in MCI and AD.
carriers and noncarriers present with distinct phenotypes of cerebral vascular dysfunction during hemodynamic orthostatic challenge. Unique cerebral and peripheral vascular compensation observed in carriers may be lost as AD progresses.
随着年龄增长，直立位时脑血流量的维持会受损，并与认知能力下降相关，但载脂蛋白E4等位基因（ε4）的影响尚不清楚。
纳入108名被诊断为认知正常（NC）、轻度认知障碍（MCI）或阿尔茨海默病（AD）的老年人（ε4携带者47名，非携带者61名）。在从坐位到站立位的转换过程中，使用经颅多普勒超声评估大脑中动脉血流速度（MCAv），并连续记录逐搏平均动脉血压（MAP）。比较不同基因型以及疾病进展过程中预期性和直立性诱导的MCAv和MAP反应。
与非携带者相比，认知正常的ε4携带者在预期性反应中MCAv增加幅度更大，直立位时MCAv下降幅度更大，外周MAP对直立位反应的潜伏期更短。在疾病进展过程中，MCAv和MAP反应延迟且减弱，MCI和AD患者的基因型之间没有差异。
在血流动力学直立性挑战期间，ε4携带者和非携带者表现出不同的脑血管功能障碍表型。随着AD的进展，ε4携带者中观察到的独特的脑和外周血管代偿可能会丧失。
