Brain functional topology differs by sex in cognitively normal older adults.
Brain functional topology differs by sex in cognitively normal older adults.
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DOI：
10.1093/texcom/tgac023
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发表时间：
2022
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迟发性阿尔茨海默病(AD)是最常见的痴呆症，其中近70%的患者是女性。我们假设女性比男性表现出更差的全球FC指标，并进一步假设女性FC指标与认知分数之间存在性别特定的正相关。我们研究了阿尔茨海默病神经成像计划队列中认知健康的个体，并进行了静息状态的功能磁共振成像。从图论分析和功能连接学获得的指标被用来评估全球/地区在功能整合和分离方面的性别差异，考虑到淀粉样蛋白的状态和APOE E4的贡献。采用带有协变量(教育、利手、载脂蛋白E4的存在和受试者内效应)的线性混合效应模型来评估性别差异。评估了词汇学习和记忆能力与拓扑网络属性之间的关系。与男性相比，女性在全球和区域功能网络指标上的程度要低得多。探索性关联分析表明，总体聚集系数越高，女性的健忘率越低，男性的认知得分越低。总体而言，女性在静息状态、功能、网络拓扑和连通性方面的衡量标准较低。这一因素可以在他们对AD的不同脆弱性中发挥作用。三分之二的AD患者是女性，但这些性别差异的原因尚不清楚。当这种迟发性痴呆症出现时，已经太晚了，无法理解这种性别差异的潜在原因。对认知健康的老年人群的研究是深入探索这种最常见形式痴呆症的不同脆弱性的基本途径。目前，65岁及以上的美国人中有620万人患有痴呆症，这意味着65岁及以上的人中每9人中就有1人(11.3%)受到阿尔茨海默氏症的影响。静息状态、功能网络拓扑和连通性等方法可能在理解和阐明与迟发性痴呆综合征相关的性别依赖差异方面发挥关键作用。
Late onset Alzheimer’s disease (AD) is the most common form of dementia, in which almost 70% of patients are women. We hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women. We studied cognitively healthy individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of APOE E4. Linear mixed effect models with covariates (education, handedness, presence of apolipoprotein [APOE] E4 and intra-subject effect) were utilized to evaluate sex differences. The associations of verbal learning and memory abilities with topological network properties were assessed. Women had a significantly lower magnitude of the global and regional functional network metrics compared to men. Exploratory association analysis showed that higher global clustering coefficient was associated with lower percent forgetting in women and worse cognitive scores in men. Women overall show lower magnitude on measures of resting state functional network topology and connectivity. This factor can play a role in their different vulnerability to AD. Two thirds of AD patients are women but the reasons for these sex difference are not well understood. When this late onset form dementia arises is too late to understand the potential causes of this sex disparities. Studies on cognitively healthy elderly population are a fundamental approach to explore in depth this different vulnerability to the most common form of dementia, currently affecting 6.2 million Americans aged 65 and older are, which means that >1 in 9 people (11.3%) 65 and older are affected by AD. Approaches such as resting-state functional network topology and connectivity may play a key role in understanding and elucidate sex-dependent differences relevant to late-onset dementia syndromes.