Kapoor Arunima, Dutt Shubir, Engstrom Allison C, Alitin John Paul M, Lohman Trevor, Sible Isabel J, Marshall Anisa, Shenasa Fatemah, Gaubert Aimée, Bradford David Robert, Sordo Lorena, Shao Xingfeng, Rodgers Kathleen, Head Elizabeth, Wang Danny Jj, Nation Daniel A
Department of Psychological Science, University of California, Irvine.
Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco.
Neurology. 2025 Jan 14;104(1):e210210. doi: 10.1212/WNL.0000000000210210. Epub 2025 Jan 9.
Cerebrovascular reactivity (CVR) represents the ability of cerebral blood vessels to regulate blood flow in response to vasoactive stimuli and is related to cognition in cerebrovascular and neurodegenerative conditions. However, few studies have examined CVR in the medial temporal lobe, known to be affected early in Alzheimer disease and to influence memory function. We aimed to examine whether medial temporal CVR is associated with memory function in older adults with and without mild cognitive impairment (MCI).
In this observational study, independently living older adults free of dementia or stroke were recruited from the community and underwent brain MRI, neuropsychological assessment, and blood draw in an academic research setting. pCASL MRI quantified medial temporal lobe cerebral perfusion during CVR response to hypercapnia. Hypercapnia was induced by visually guided breathing exercises (15 seconds breath holds) during capnographic monitoring. MCI diagnosis and memory performance were assessed through comprehensive neuropsychological assessment. Aβ42/40 and pTau181 levels were quantified in blood plasma. Logistic and hierarchical linear regression examined medial temporal CVR in relation to MCI diagnosis and memory function.
In a sample of 144 older adults (mean age = 69.6 years; SD = 7.4%; 34.7% male; mean education = 16.6 years, SD = 2.3), CVR to hypercapnia in the medial temporal lobe was attenuated in individuals with MCI after adjusting for age, sex, education, apolipoprotein ε4 carrier status, Aβ42/40 and pTau181 levels, and vascular risk factors (OR = 0.87, 95% CI [0.77-0.97], = 0.013). Cerebrovascular reactivity to hypercapnia was associated with verbal memory performance for stories (B = 0.33, 95% CI [0.09-0.57], = 0.009), a word list (B = 0.10, 95% CI [0.001-0.20], = 0.048), and visual memory (B = 0.33, 95% CI [0.09-0.57], = 0.008).
Deficits in medial temporal CVR are observed in older adults with MCI and are related to worse memory function. Findings suggest that medial temporal cerebrovascular dysfunction is related to cognition and memory before the onset of dementia, independent of changes in Alzheimer pathophysiologic markers. Limitations of the study include the cross-sectional design. Future longitudinal studies are warranted to examine whether early cerebrovascular changes can predict progressive memory decline.
脑血管反应性（CVR）代表脑血管在响应血管活性刺激时调节血流的能力，并且与脑血管疾病和神经退行性疾病中的认知相关。然而，很少有研究考察内侧颞叶的CVR，内侧颞叶在阿尔茨海默病早期就会受到影响且会影响记忆功能。我们旨在研究有或无轻度认知障碍（MCI）的老年人中内侧颞叶CVR是否与记忆功能相关。
在这项观察性研究中，从社区招募独立生活、无痴呆或中风的老年人，并在学术研究环境中对其进行脑部MRI、神经心理学评估和采血。伪连续动脉自旋标记（pCASL）MRI在对高碳酸血症的CVR反应期间量化内侧颞叶脑灌注。通过在二氧化碳描记监测期间进行视觉引导的呼吸练习（屏气15秒）诱导高碳酸血症。通过全面的神经心理学评估来评估MCI诊断和记忆表现。定量测定血浆中的Aβ42/40和pTau181水平。逻辑回归和分层线性回归研究内侧颞叶CVR与MCI诊断和记忆功能的关系。
在144名老年人的样本中（平均年龄=69.6岁；标准差=7.4%；男性占34.7%；平均受教育年限=16.6年，标准差=2.3），在调整年龄、性别、受教育程度、载脂蛋白ε4携带者状态、Aβ42/40和pTau181水平以及血管危险因素后，MCI个体对高碳酸血症的内侧颞叶CVR减弱（比值比=0.87，95%置信区间[0.77 - 0.97]，P = 0.013）。对高碳酸血症的脑血管反应性与故事的言语记忆表现相关（B = 0.33，95%置信区间[0.09 - 0.57]，P = 0.009）、单词表的言语记忆表现相关（B = 0.10，95%置信区间[0.001 - 0.20]，P = 0.048）以及视觉记忆相关（B = 0.33，95%置信区间[0.09 - 0.57]，P = 0.008）。
在患有MCI的老年人中观察到内侧颞叶CVR缺陷，并且与较差的记忆功能相关。研究结果表明，内侧颞叶脑血管功能障碍在痴呆发作之前与认知和记忆相关，独立于阿尔茨海默病病理生理标志物的变化。该研究的局限性包括横断面设计。未来有必要进行纵向研究以检验早期脑血管变化是否可以预测进行性记忆衰退。
