Department of Physical Therapy, Rehabilitation Science, and Athletic Training, School of Health Professions, University of Kansas Medical Center, Kansas City, KS, USA; University of Kansas Alzheimer's Disease Research Center, Fairway, KS, USA.
Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
Neurobiol Aging. 2022 Jun;114:15-26. doi: 10.1016/j.neurobiolaging.2022.02.014. Epub 2022 Mar 4.
The etiology of cognitive dysfunction associated with Alzheimer's disease (AD) and dementia is multifactorial. Yet, mechanistic interactions among key neurobiological factors linked to AD pathology are unclear. This study tested the effect of interactions between cerebrovascular function, individual genotype, and structural brain pathology on response inhibition performance, an early and sensitive indicator of cognitive executive dysfunction with aging. We quantified cerebrovascular response (CVR) to moderate-intensity aerobic exercise using transcranial doppler ultrasound and global amyloid-beta (Aβ) deposition using positron emission tomography in a group of cognitively normal older adults genotyped as APOE4 carriers and noncarriers. We quantified response inhibition during a cognitive Stroop test. Individuals with blunted CVR possessed greater Aβ deposition. There was CVR-by-carrier status-by-Aβ interaction on response inhibition. Blunted CVR was associated with impaired response inhibition specifically in APOE4 carriers. Despite having greater Aβ deposition, APOE4 carriers with higher CVR demonstrated better response inhibition. Cerebrovascular interactions with individual genotype and structural brain pathology may provide a physiologically-informed target for precision-medicine approaches for early treatment and prevention of cognitive dysfunction with aging.
与阿尔茨海默病（AD）和痴呆相关的认知功能障碍的病因是多因素的。然而，与 AD 病理相关的关键神经生物学因素之间的机制相互作用尚不清楚。本研究测试了脑血管功能、个体基因型和结构脑病理学之间的相互作用对反应抑制性能的影响，反应抑制是一种与衰老相关的认知执行功能障碍的早期和敏感指标。我们使用经颅多普勒超声量化了认知正常的老年人在中度强度有氧运动时的脑血管反应（CVR），并用正电子发射断层扫描量化了整体淀粉样蛋白-β（Aβ）沉积。我们在认知 Stroop 测试中量化了反应抑制。CVR 迟钝的个体具有更大的 Aβ沉积。反应抑制存在 CVR-携带者状态-Aβ 相互作用。CVR 迟钝与 APOE4 携带者的反应抑制受损有关。尽管 APOE4 携带者的 Aβ 沉积更多，但 CVR 较高的 APOE4 携带者表现出更好的反应抑制。个体基因型和结构脑病理学的脑血管相互作用可能为针对衰老相关认知功能障碍的早期治疗和预防的精准医学方法提供生理信息目标。
