Mild cognitive impairment (MCI) has been frequently interpreted as a transitional phase between healthy cognitive aging and dementia, particularly of the Alzheimer's disease (AD) type. Of note, few studies explored that transition from a multifactorial perspective, taking into consideration the effect of basic factors such as biological sex. In the present study 96 subjects with MCI (37 males and 59 females) were followed-up and divided into two subgroups according to their clinical outcome: “progressive” MCI (pMCI = 41), if they fulfilled the diagnostic criteria for AD at the end of follow-up; and “stable” MCI (sMCI = 55), if they remained with the initial diagnosis. Different markers were combined to characterize sex differences between groups, including magnetoencephalography recordings, cognitive performance, and brain volumes derived from magnetic resonance imaging. Results indicated that the pMCI group exhibited higher low-frequency activity, lower scores in neuropsychological tests and reduced brain volumes than the sMCI group, being these measures significantly correlated. When sex was considered, results revealed that this pattern was mainly due to the influence of the females’ sample. Overall, females exhibited lower cognitive scores and reduced brain volumes. More interestingly, females in the pMCI group showed an increased theta activity that correlated with a more abrupt reduction of cognitive and volumetric scores as compared with females in the sMCI group and with males in the pMCI group. These findings suggest that females’ brains might be more vulnerable to the effects of AD pathology, since regardless of age, they showed signs of more pronounced deterioration than males.

轻度认知障碍（MCI）经常被解释为健康认知衰老和痴呆之间的过渡阶段，尤其是阿尔茨海默病（AD）类型。值得注意的是，很少有研究从多因素角度探讨这种转变，并考虑到生物性别等基本因素的影响。在本研究中，对 96 名 MCI 受试者（37 名男性和 59 名女性）进行了随访，并根据临床结果分为两个亚组：“进行性”MCI (pMCI = 41)，如果他们在治疗时满足 AD 诊断标准。随访结束；和“稳定”MCI (sMCI = 55)，如果它们保持初始诊断。结合不同的标记来表征群体之间的性别差异，包括脑磁图记录、认知表现和磁共振成像得出的脑体积。结果表明，pMCI 组比 sMCI 组表现出更高的低频活动、更低的神经心理学测试分数和更少的脑容量，这些指标显着相关。当考虑性别时，结果显示这种模式主要是受到女性样本的影响。总体而言，女性的认知得分较低，脑容量也较小。更有趣的是，与 sMCI 组的女性和 pMCI 组的男性相比，pMCI 组的女性表现出更高的 θ 活动，这与认知和体积分数的更​​突然下降相关。这些发现表明，女性的大脑可能更容易受到 AD 病理学的影响，因为无论年龄如何，女性的大脑都比男性表现出更明显的退化迹象。