Ziyu Liu ¹ Yaoli He ² Simeng Cui ¹ Liangjun Dang ¹ Binyan Zhang ³ Jin Wang ¹ Wenhui Lu ¹ Kang Huo ¹ Yu Jiang ⁴ Chen Chen ¹ Ling Gao ¹ Shan Wei ¹ Yi Zhao ¹ Ningwei Hu ¹ Jingyi Wang ⁵ Hong Lv ^6,7* Qiumin Qu ^8* Suhang Shang ^1*

• ¹ Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
• ² Department of Neurology, Baoji Central Hospital, Baoji, Shaanxi Province, China
• ³ Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University, Xi'an, China
• ⁴ Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
• ⁵ Huyi Hospital of Traditional Chinese Medicine, Xi'an, China
• ⁶ Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
• ⁷ Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China
• ⁸ Department of Neurology, Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

Background: Plasma beta-amyloid (Aβ) are important biomarkers for Alzheimer’s disease and cognitive impairment (CI), but results are controversial. It remains unclear whether hypertension modulates their relationship. This cross-sectional study investigates whether hypertension moderates the relationship between plasma Aβ and cognitive impairment (CI). Methods: This cross-sectional study included 1488 subjects ≥40 years from rural areas of northwestern China. CI was defined as a Mini-Mental State Examination score lower than the cutoff. Firstly, plasma Aβ40, Aβ42, Aβ42/Aβ40 were analyzed as restricted cubic spline. Then, categories of combined plasma Aβ were created by making bisection of plasma Aβ according to average and combining them as L-Aβ40 and L-Aβ42, H-Aβ40 and L-Aβ42, L-Aβ40 and H-Aβ42, H-Aβ40 and H-Aβ42. Decreased plasma Aβ40 was defined as < 25th percentile. Multivariate logistic regression examined the relationship between plasma Aβ and CI in total population, the hypertension subgroup and the non-hypertension subgroup. Results: 737 participants (49.5%) had hypertension and 189 participants (12.7%) had CI. Simultaneously elevated plasma Aβ40 and Aβ42 is associated with CI in hypertension (H-Aβ40 and H-Aβ42 vs. L-Aβ40 and L-Aβ42, 21.1% vs.10.7%, P=0.033; OR=1.984 [95% CI, 1.067–3.691], P = 0.030) but not in the non-hypertension. Decreased plasma Aβ40 is associated with CI in the non-hypertension (14.9% vs 9.2%, P=0.026; OR =1.728 [95% CI, 1.018-2.931], P = 0.043) but not in the hypertension. Conclusion: Hypertension is an important modulator in the relationship between plasma Aβ and CI. Simultaneously elevated plasma Aβ40 and Aβ42 in the hypertension, and decreased plasma Aβ40 in the non-hypertension, may be risk factors for CI. These findings emphasize the need to consider hypertension in CI detection.