Ahern Jonathan, Boyle Mary Et, Thompson Wesley K, Fan Chun Chieh, Loughnan Robert
Department of Cognitive Science, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Center for Human Development, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92161, USA.
medRxiv. 2024 Mar 15:2024.03.13.24304253. doi: 10.1101/2024.03.13.24304253.
Iron is an essential nutrient which can only be absorbed through an individual's diet. Excess iron accumulates in organs throughout the body including the brain. Iron dysregulation in the brain is commonly associated with neurodegenerative diseases like Alzheimer's disease and Parkinson's Disease (PD). Our previous research has shown that a pattern of iron accumulation in motor regions of the brain related to a genetic iron-storage disorder called hemochromatosis is associated with an increased risk of PD. To understand how diet and lifestyle factors relate to this brain endophenotype and risk of PD we analyzed the relationship between these measures, estimates of nutrient intake, and diet and lifestyle preference using data from UK Biobank.
Using distinct imaging and non-imaging samples (20,477 to 28,388 and 132,023 to 150,603 participants, respectively), we performed linear and logistic regression analyses using estimated dietary nutrient intake and food preferences to predict a) brain iron accumulation score (derived from T2-Weighted Magnetic Resonance Imaging) and b) PD risk. In addition, we performed a factor analysis of diet and lifestyle preferences to investigate if latent lifestyle factors explained significant associations. Finally, we performed an instrumental variable regression of our results related to iron accumulation and PD risk to identify if there were common dietary and lifestyle factors that were jointly associated with differences in brain iron accumulation and PD risk.
We found multiple highly significant associations with measures of brain iron accumulation and preferences for alcohol (factor 7: t=4.02, p=0.0003), exercise (factor 11: t=-4.31, p=0.0001), and high-sugar foods (factor 2: t=-3.73, p=0.0007). Preference for alcohol (factor 7: t=-5.83, p<1×10), exercise (factor 11: t=-7.66, p<1×10), and high sugar foods (factor 2: t=6.03, p<1×10) were also associated with PD risk. Instrumental variable regression of individual preferences revealed a significant relationship in which dietary preferences associated with higher brain iron levels also appeared to be linked to a lower risk for PD (p=0.004). A similar relationship was observed for estimates of nutrient intake (p=0.0006). Voxel-wise analysis of i) high-sugar and ii) alcohol factors confirmed T2-weighted signal differences consistent with iron accumulation patterns in motor regions of the brain including the cerebellum and basal ganglia.
Dietary and lifestyle factors and preferences, especially those related to carbohydrates, alcohol, and exercise, are related to detectable differences in brain iron accumulation and alterations in risk of PD, suggesting a potential avenue for lifestyle interventions that could influence risk.
铁是一种必需营养素，只能通过个体饮食吸收。过量的铁会在包括大脑在内的全身各器官中积累。大脑中铁调节异常通常与阿尔茨海默病和帕金森病（PD）等神经退行性疾病相关。我们之前的研究表明，与一种名为血色素沉着症的遗传性铁储存障碍相关的大脑运动区域铁积累模式与PD风险增加有关。为了了解饮食和生活方式因素如何与这种大脑内表型及PD风险相关，我们使用英国生物银行的数据分析了这些指标、营养素摄入量估计值以及饮食和生活方式偏好之间的关系。
我们分别使用不同的成像和非成像样本（分别为20477至28388名和132023至150603名参与者），通过估计的膳食营养素摄入量和食物偏好进行线性和逻辑回归分析，以预测：a）脑铁积累评分（源自T2加权磁共振成像）和b）PD风险。此外，我们对饮食和生活方式偏好进行了因子分析，以研究潜在的生活方式因素是否能解释显著关联。最后，我们对与铁积累和PD风险相关的结果进行了工具变量回归分析，以确定是否存在与脑铁积累差异和PD风险共同相关的常见饮食和生活方式因素。
我们发现了多个与脑铁积累指标以及酒精偏好（因子7：t = 4.02，p = 0.0003）、运动偏好（因子11：t = -4.31，p = 0.0001）和高糖食物偏好（因子2：t = -3.73，p = 0.0007）高度显著的关联。酒精偏好（因子7：t = -5.83，p < 1×10）、运动偏好（因子11：t = -7.66，p < 1×10）和高糖食物偏好（因子2：t = 6.03，p < 1×10）也与PD风险相关。个体偏好的工具变量回归显示出显著关系，即与较高脑铁水平相关的饮食偏好似乎也与较低的PD风险相关（p = 0.004）。营养素摄入量估计值也观察到类似关系（p = 0.0006）。对i）高糖和ii）酒精因子的体素分析证实了与包括小脑和基底神经节在内的大脑运动区域铁积累模式一致的T2加权信号差异。
饮食和生活方式因素及偏好，尤其是与碳水化合物、酒精和运动相关的因素，与脑铁积累的可检测差异以及PD风险变化相关，这表明生活方式干预可能是影响风险的潜在途径。
