Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study.
Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study.
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DOI：
10.1177/0271678x211021313
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Okonkwo OC
中科院分区：
文献类型：
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作者：
Wang R;Oh JM;Motovylyak A;Ma Y;Sager MA;Rowley HA;Johnson KM;Gallagher CL;Carlsson CM;Bendlin BB;Johnson SC;Asthana S;Eisenmenger L;Okonkwo OC
脑灌注不足被认为会导致阿尔茨海默病的认知能力下降，但认知健康的成年人脑灌注的自然轨迹尚未得到充分研究。这项纵向研究包含950名参与者（40 - 89岁），他们在首次就诊时认知未受损。我们研究了脑灌注与年龄相关的变化，以及它们与载脂蛋白E（APOE）基因型、生物性别和心脏代谢指标的关联。在随访期间（0.13 - 8.24年），年龄增长与脑灌注减少显著相关，在全脑灰质（β = -1.43）、海马体（-1.25）、额上回（-1.70）、额中回（-1.99）、后扣带回（-2.46）和楔前叶（-2.14），所有P值均<0.01。与男性ɛ4携带者相比，女性ɛ4携带者随着年龄增长，全脑和局部脑灌注下降更快，而男性和女性非ɛ4携带者脑灌注与年龄相关的下降相似。较差的心脏代谢状况（即血压升高、体重指数增加、总胆固醇升高和血糖升高）在所有就诊时都与较低的脑灌注相关。当在模型中调整随时间变化的心脏代谢指标时，性别和APOE - ɛ4对年龄相关脑灌注轨迹的协同效应大幅减弱。我们的研究结果表明，APOE基因型和性别相互作用影响中年到晚年的脑灌注轨迹。这种效应可能部分由心脏代谢改变所解释。
Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer’s disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40—89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13—8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (β=−1.43), hippocampus (−1.25), superior frontal gyrus (−1.70), middle frontal gyrus (−1.99), posterior cingulate (−2.46), and precuneus (−2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.