Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Institute of Neurosciences, Department of Biomedicine, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
Eur J Neurol. 2022 Dec;29(12):3623-3632. doi: 10.1111/ene.15531. Epub 2022 Sep 9.
Sex is believed to drive heterogeneity in Alzheimer's disease (AD), although evidence in early-onset AD (EOAD; <65 years) is scarce.
We included 62 EOAD patients and 44 healthy controls (HCs) with core AD cerebrospinal fluid (CSF) biomarkers, neurofilament light chain levels, neuropsychological assessment, and 3-T magnetic resonance imaging. We measured cortical thickness (CTh) and hippocampal subfield volumes (HpS) using FreeSurfer. Adjusted linear models were used to analyze sex-differences and the relationship between atrophy and cognition.
Compared to same-sex HCs, female EOAD subjects showed greater cognitive impairment and broader atrophy burden than male EOAD subjects. In a direct female-EOAD versus male-EOAD comparison, there were slight differences in temporal CTh, with no differences in cognition or HpS. CSF tau levels were higher in female EOAD than in male EOAD subjects. Greater atrophy was associated with worse cognition in female EOAD subjects.
At diagnosis, there are sex differences in the pattern of cognitive impairment, atrophy burden, and CSF tau in EOAD, suggesting there is an influence of sex on pathology spreading and susceptibility to the disease in EOAD.
性别被认为是导致阿尔茨海默病（AD）异质性的因素，尽管在早发性 AD（EOAD；<65 岁）中证据较少。
我们纳入了 62 名 EOAD 患者和 44 名健康对照者（HCs），这些患者和对照者具有 AD 核心脑脊液（CSF）生物标志物、神经丝轻链水平、神经心理学评估和 3-T 磁共振成像。我们使用 FreeSurfer 测量皮质厚度（CTh）和海马亚区体积（HpS）。采用调整后的线性模型分析性别差异以及萎缩与认知之间的关系。
与同性别 HCs 相比，女性 EOAD 患者的认知障碍和萎缩负担均大于男性 EOAD 患者。在女性 EOAD 与男性 EOAD 的直接比较中，颞叶 CTh 存在细微差异，认知或 HpS 无差异。女性 EOAD 患者的 CSF tau 水平高于男性 EOAD 患者。女性 EOAD 患者的萎缩程度与认知能力下降呈正相关。
在 EOAD 诊断时，女性在认知障碍模式、萎缩负担和 CSF tau 方面存在性别差异，这表明性别对 EOAD 中的病理传播和疾病易感性有影响。
