Low testosterone levels relate to poorer cognitive function in women in an APOE-ε4-dependant manner.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Melanie A Dratva, Sarah J Banks, Matthew S Panizzon, Douglas Galasko, Erin E Sundermann
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引用次数: 0

Abstract

Background: Past research suggests that low testosterone levels relate to poorer cognitive function and higher Alzheimer's disease (AD) risk; however, these findings are inconsistent and are mostly derived from male samples, despite similar age-related testosterone decline in females. Both animal and human studies demonstrate that testosterone's effects on brain health may be moderated by apolipoprotein E ε4 allele (APOE-ε4) carrier status, which may explain some previous inconsistencies. We examined how testosterone relates to cognitive function in older women versus men across healthy aging and the AD continuum and the moderating role of APOE-ε4 genotype.

Methods: Five hundred and sixty one participants aged 55-90 (155 cognitively normal (CN), 294 mild cognitive impairment (MCI), 112 AD dementia) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), who had baseline cognitive and plasma testosterone data, as measured by the Rules Based Medicine Human DiscoveryMAP Panel were included. There were 213 females and 348 males (self-reported sex assigned at birth), and 52% of the overall sample were APOE-ε4 carriers. We tested the relationship of plasma testosterone levels and its interaction with APOE-ε4 status on clinical diagnostic group (CN vs. MCI vs. AD), global, and domain-specific cognitive performance using ANOVAs and linear regression models in sex-stratified samples. Cognitive domains included verbal memory, executive function, processing speed, and language.

Results: We did not observe a significant difference in testosterone levels between clinical diagnostic groups in either sex, regrardless of APOE-ε4 status. Across clinical diagnostic group, we found a significant testosterone by APOE-ε4 interaction in females, such that lower testosterone levels related to worse global cognition, processing speed, and verbal memory in APOE-ε4 carriers only. We did not find that testosterone, nor its interaction with APOE-ε4, related to cognitive outcomes in males.

Conclusions: Findings suggest that low testosterone levels in older female APOE-ε4 carriers across the aging-MCI-AD continuum may have deleterious, domain-specific effects on cognitive performance. Although future studies including additional sex hormones and longitudinal cognitive trajectories are needed, our results highlight the importance of including both sexes and considering APOE-ε4 carrier status when examining testosterone's role in cognitive health.

低睾酮水平与女性较差的认知功能有关,其方式取决于 APOE-ε4。
背景:过去的研究表明,睾酮水平低与认知功能较差和阿尔茨海默病(AD)风险较高有关;然而,这些研究结果并不一致,而且大多来自男性样本,尽管女性也存在与年龄相关的睾酮下降。动物和人体研究都表明,睾酮对大脑健康的影响可能会受到载脂蛋白 E ε4等位基因(APOE-ε4)携带者身份的影响,这可能解释了之前的一些不一致之处。我们研究了睾酮与老年女性认知功能的关系,以及APOE-ε4基因型的调节作用:研究人员纳入了来自阿尔茨海默病神经影像学倡议(ADNI)的 561 名 55-90 岁参与者(155 名认知正常者(CN)、294 名轻度认知障碍者(MCI)、112 名 AD 痴呆者),这些参与者都有基线认知和血浆睾酮数据,这些数据是由基于规则的医学人类发现 MAP 小组测量的。其中有 213 名女性和 348 名男性(出生时自我报告的性别),总体样本中有 52% 是 APOE-ε4 携带者。我们在性别分层样本中使用方差分析和线性回归模型检验了血浆睾酮水平及其与 APOE-ε4 状态的交互作用与临床诊断组(CN vs. MCI vs. AD)、整体和特定领域认知能力的关系。认知领域包括言语记忆、执行功能、处理速度和语言:我们没有观察到临床诊断组之间男女睾酮水平的显著差异,与 APOE-ε4 状态无关。在不同的临床诊断组中,我们发现女性的睾酮与APOE-ε4之间存在显著的交互作用,即睾酮水平越低,APOE-ε4携带者的整体认知能力、处理速度和语言记忆力越差。我们没有发现睾酮或其与APOE-ε4的相互作用与男性的认知结果有关:研究结果表明,老年女性APOE-ε4携带者在整个衰老-MCI-AD过程中的低睾酮水平可能会对认知能力产生有害的、特定领域的影响。尽管未来的研究还需要包括更多的性激素和纵向认知轨迹,但我们的研究结果强调了在研究睾酮在认知健康中的作用时,将两性都包括在内并考虑 APOE-ε4 携带者状态的重要性。
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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