Serum uric acid, a natural antioxidant, may have a protective effect on the progression of Alzheimer's disease (AD). To investigate the effect of serum uric acid on longitudinal cognitive and brain metabolic changes, we utilized data on baseline serum uric acid levels, APOE genotyping, and longitudinal cognitive scores from the Alzheimer's Disease Neuroimaging Initiative for 1,343 participants with normal cognition (NC), mild cognitive impairment (MCI), or dementia. In 979 participants, brain metabolism was measured using ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) images. Higher serum uric acid levels exhibited a detrimental effect on NC, whereas a protective trend was observed in individuals with cognitive impairment. Interestingly, higher uric acid levels were associated with a slower decline in cognitive scores and brain metabolism in females with MCI, and this effect was found in APOE4 carriers, but not in non-carriers. Longitudinal AD-like patterns of brain metabolism on FDG-PET images also appeared to mediate the effects of baseline uric acid levels on longitudinal cognitive decline. In summary, higher serum uric acid may interact with APOE4 to alleviate longitudinal metabolic changes and cognitive decline in female MCI patients.

血清尿酸是一种天然抗氧化剂，可能对阿尔茨海默病 (AD) 的进展具有保护作用。为了研究血清尿酸对纵向认知和大脑代谢变化的影响，我们利用了来自阿尔茨海默病神经影像学计划的基线血清尿酸水平、APOE基因分型和纵向认知评分的数据，这些数据来自 1,343 名认知正常 (NC)、轻度认知障碍 (MCI) 或痴呆症。在 979 名参与者中，使用¹⁸F-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）图像。较高的血清尿酸水平对 NC 有不利影响，而在有认知障碍的个体中观察到保护趋势。有趣的是，在患有 MCI 的女性中，较高的尿酸水平与认知评分和脑代谢的下降较慢有关，这种影响在APOE4携带者中发现，但在非携带者中没有。FDG-PET 图像上的纵向 AD 样脑代谢模式似乎也介导了基线尿酸水平对纵向认知能力下降的影响。总之，较高的血清尿酸可能与APOE4相互作用，以减轻女性 MCI 患者的纵向代谢变化和认知能力下降。