Gentreau Mélissa, Miguet Maud, Affatato Oreste, Rukh Gull, Schiöth Helgi Birgir
Functional Pharmacology and Neuroscience, Department of Surgical Sciences, University of Uppsala, 751 23 Uppsala, Sweden.
Sport, Physical Activity, Rehabilitation and Movement for Performance and Health (SAPRéM), Université d'Orléans, 45067 Orléans, France.
Brain Commun. 2024 Nov 20;6(6):fcae417. doi: 10.1093/braincomms/fcae417. eCollection 2024.
While statins are routinely prescribed to prevent cardiovascular diseases, their effects on brain alterations remain largely unknown. Very few studies have examined the differences in brain volumes between statin users and non-users, and existing research has yielded inconsistent results. This cross-sectional study aims to investigate the association between statin use at baseline and global and specific brain volumes measured 9 years later in a large population-based sample of middle-aged and older adults. Participants from the UK Biobank without neurological and psychiatric disorders consisted of 3285 statin users (mean 60 years and 69% males) and 36 229 non-users (mean 55 years and 46% males). We used linear models to estimate the mean volumetric differences between statin users and non-users while adjusting for UK Biobank assessment centre, age, sex, ethnicity, education, apolipoprotein E ɛ4 status, Townsend deprivation index, antidepressant use, intracranial volume, lifestyle factors (alcohol intake frequency, smoking and physical activity) and health-related conditions (body mass index, blood pressure, diabetes, coronary heart disease, stroke, head injury, depression and insomnia). Moreover, mediation analysis was performed to evaluate whether the association between statin use and global brain volumes was mediated by total serum cholesterol concentration. Statin use was associated with lower grey matter volume [β = -1575 mm (-2358, -791)], with 20% of this association mediated by total serum cholesterol concentration. Statin use was also associated with lower peripheral cortical grey matter volumes [β = -1448 mm (-2227, -668)] and higher white matter hyperintensity [β = 0.11 mm (0.07, 0.15)]. However, white matter volume did not differ significantly between statin users and non-users. Further analyses revealed that volumes of thalamus, pallidum, hippocampus, nucleus accumbens and other regions of the temporal lobe were smaller among statin users compared with non-users. This study showed that statin use is associated with higher white matter hyperintensity volumes and lower total and peripheral cortical grey matter volumes 9 years later, indicative of the brain's ageing process. Moreover, the observed grey matter alterations were partially explained by statin-induced total serum cholesterol reduction. This study emphasizes the potential direct and indirect effects of statins on brain volume.
虽然他汀类药物通常用于预防心血管疾病，但其对大脑改变的影响在很大程度上仍不清楚。很少有研究调查他汀类药物使用者和非使用者之间脑容量的差异，现有研究结果并不一致。这项横断面研究旨在调查在一个基于人群的中老年大样本中，基线时使用他汀类药物与9年后测量的全脑和特定脑容量之间的关联。来自英国生物银行且无神经和精神疾病的参与者包括3285名他汀类药物使用者（平均年龄60岁，男性占69%）和36229名非使用者（平均年龄55岁，男性占46%）。我们使用线性模型来估计他汀类药物使用者和非使用者之间的平均体积差异，同时对英国生物银行评估中心、年龄、性别、种族、教育程度、载脂蛋白Eɛ4状态、汤森德剥夺指数、抗抑郁药使用情况、颅内体积、生活方式因素（饮酒频率、吸烟和身体活动）以及健康相关状况（体重指数、血压、糖尿病、冠心病、中风、头部受伤、抑郁症和失眠）进行调整。此外，进行了中介分析，以评估他汀类药物使用与全脑容量之间的关联是否由总血清胆固醇浓度介导。使用他汀类药物与较低的灰质体积相关[β = -1575 mm³（-2358，-791）]，其中20%的关联由总血清胆固醇浓度介导。使用他汀类药物还与较低的外周皮质灰质体积[β = -1448 mm³（-2227，-668）]和较高的白质高信号[β = 0.11 mm³（0.07，0.15）]相关。然而，他汀类药物使用者和非使用者之间的白质体积没有显著差异。进一步分析显示，与非使用者相比，他汀类药物使用者的丘脑、苍白球、海马体、伏隔核和颞叶其他区域的体积较小。这项研究表明，使用他汀类药物与9年后较高的白质高信号体积以及较低的全脑和外周皮质灰质体积相关，这表明大脑的衰老过程。此外，观察到的灰质改变部分可由他汀类药物引起的总血清胆固醇降低来解释。这项研究强调了他汀类药物对脑容量的潜在直接和间接影响。
