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, Minnesota, USA.
Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Alzheimers Dement. 2025 May;21(5):e70229. doi: 10.1002/alz.70229.
Maintenance of cerebral blood flow during orthostasis is impaired with aging and associated with cognitive decline, but the effect of the apolipoprotein ɛ4 allele (APOE4) is unknown.
Older adults (n = 108) (APOE4 carriers, n = 47; non-carriers, n = 61) diagnosed as having normal cognition (NC), mild cognitive impairment (MCI), or Alzheimer's disease (AD) underwent transcranial Doppler ultrasound assessment of middle cerebral artery blood velocity (MCAv) and beat-to-beat mean arterial blood pressure (MAP) during a sit-to-stand transition. Anticipatory and orthostasis-induced MCAv and MAP responses were compared between genotypes and diagnostic classifications.
Cognitively normal APOE4 carriers showed greater anticipatory MCAv increase, greater MCAv decrease with orthostasis, and shorter latency of peripheral MAP responses to orthostasis compared to non-carriers. MCAv and MAP responses were delayed and attenuated across the APOE4 disease continuum, with no differences between genotypes in MCI and AD.
Unique cerebral and peripheral vascular compensation observed in APOE4 carriers may be neuroprotective for AD development.
APOE4 carriers with NC show greater anticipatory increases in MCAv prior to orthostasis and decreases during orthostasis. APOE4 carriers with NC show faster peripheral MAP responses during orthostasis. APOE4 carriers with MCI and AD display loss of anticipatory MCAv responses. APOE4 carriers with MCI and AD display slower peripheral MAP responses. Unique cerebral and peripheral vascular compensation observed in APOE4 carriers may be neuroprotective for AD development.
直立位时脑血流量的维持会随着年龄增长而受损，并与认知能力下降相关，但载脂蛋白ɛ4等位基因（APOE4）的影响尚不清楚。
108名老年人（APOE4携带者47名，非携带者61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），在从坐位到站立位转换过程中接受经颅多普勒超声评估大脑中动脉血流速度（MCAv）和逐搏平均动脉血压（MAP）。比较不同基因型和诊断分类之间预期性和直立位诱发的MCAv及MAP反应。
与非携带者相比，认知正常的APOE4携带者在预期性MCAv增加、直立位时MCAv下降幅度更大，以及外周MAP对直立位反应的潜伏期更短。在APOE4疾病连续谱中，MCAv和MAP反应延迟且减弱，MCI和AD患者的基因型之间无差异。
在APOE4携带者中观察到的独特的脑和外周血管代偿可能对AD的发展具有神经保护作用。
认知正常的APOE4携带者在直立位前MCAv预期性增加更大，直立位时下降幅度更大。认知正常的APOE4携带者在直立位时外周MAP反应更快。患有MCI和AD的APOE4携带者预期性MCAv反应消失。患有MCI和AD的APOE4携带者外周MAP反应更慢。在APOE4携带者中观察到的独特的脑和外周血管代偿可能对AD的发展具有神经保护作用。
