Magalhães Thamires N C, Hicks Tracey H, Jackson T Bryan, Ballard Hannah K, Herrejon Ivan A, Bernard Jessica A
Department of Psychological and Brain Sciences, Texas A&M University, College Station, Texas, United States of America.
Vanderbilt Memory & Alzheimer's Center, Nashville, Tennessee, United States of America.
bioRxiv. 2024 Jun 25:2024.06.24.600454. doi: 10.1101/2024.06.24.600454.
Aging involves complex biological changes that affect disease susceptibility and aging trajectories. Although females typically live longer than males, they have a higher susceptibility to diseases like Alzheimer's, speculated to be influenced by menopause, and reduced ovarian hormone production. Understanding sex-specific differences is crucial for personalized medical interventions and gender equality in health. Our study aims to elucidate sex differences in regional cerebellar structure and connectivity during normal aging by investigating both structural and functional connectivity variations, with a focus on investigating these differences in the context of sex-steroid hormones. The study included 138 participants (mean age = 57(13.3) years, age range = 35-86 years, 54% women). The cohort was divided into three groups: 38 early middle-aged individuals (EMA) (mean age = 41(4.7) years), 48 late middle-aged individuals (LMA) (mean age = 58(4) years), and 42 older adults (OA) (mean age = 72(6.3) years). All participants underwent MRI scans, and saliva samples were collected for sex-steroid hormone quantification (17β-estradiol (E), progesterone (P), and testosterone (T)). We found less connectivity in females between Lobule I-IV and the cuneus, and greater connectivity in females between Crus I, Crus II, and the precuneus with increased age. Higher 17β-estradiol levels were linked to greater connectivity in Crus I and Crus II cerebellar subregions. Analyzing all participants together, testosterone was associated with both higher and lower connectivity in Lobule I-IV and Crus I, respectively, while higher progesterone levels were linked to lower connectivity in females. Structural differences were observed, with EMA males having larger volumes compared to LMA and OA groups, particularly in the right I-IV, right Crus I, right V, and right VI. EMA females showed higher volumes in the right lobules V and VI. These results highlight the significant role of sex hormones in modulating cerebellar connectivity and structure across adulthood, emphasizing the need to consider sex and hormonal status in neuroimaging studies to better understand age-related cognitive decline and neurological disorders.
衰老涉及复杂的生物学变化，这些变化会影响疾病易感性和衰老轨迹。虽然女性通常比男性寿命更长，但她们对阿尔茨海默病等疾病的易感性更高，据推测这受到更年期以及卵巢激素分泌减少的影响。了解性别差异对于个性化医疗干预和健康领域的性别平等至关重要。我们的研究旨在通过调查结构和功能连接性变化，阐明正常衰老过程中小脑区域结构和连接性的性别差异，重点是在性类固醇激素的背景下研究这些差异。该研究包括138名参与者（平均年龄 = 57(13.3)岁，年龄范围 = 35 - 86岁，54%为女性）。该队列分为三组：38名早中年个体（EMA）（平均年龄 = 41(4.7)岁），48名晚中年个体（LMA）（平均年龄 = 58(4)岁），以及42名老年人（OA）（平均年龄 = 72(6.3)岁）。所有参与者均接受了MRI扫描，并采集了唾液样本用于性类固醇激素定量（17β - 雌二醇（E）、孕酮（P）和睾酮（T））。我们发现，小叶I - IV与楔叶之间的连接性在女性中较低，而随着年龄增长，女性中 Crus I、Crus II与楔前叶之间的连接性更高。较高的17β - 雌二醇水平与Crus I和Crus II小脑亚区域更强的连接性相关。综合分析所有参与者，睾酮分别与小叶I - IV和Crus I中较高和较低的连接性相关，而较高的孕酮水平与女性较低的连接性相关。观察到结构差异，与LMA组和OA组相比，EMA男性的体积更大，特别是在右侧I - IV、右侧Crus I、右侧V和右侧VI。EMA女性在右侧小叶V和VI中显示出更大的体积。这些结果突出了性激素在调节整个成年期小脑连接性和结构方面的重要作用，强调在神经影像学研究中需要考虑性别和激素状态，以更好地理解与年龄相关的认知衰退和神经系统疾病。
