Matthews Dawn C, Davies Michelle, Murray John, Williams Schantel, Tsui Wai H, Li Yi, Andrews Randolph D, Lukic Ana, McHugh Pauline, Vallabhajosula Shankar, de Leon Mony J, Mosconi Lisa
ADM Diagnostics, Chicago, USA.
Department of Psychiatry, New York University School of Medicine, New York, USA.
Adv J Mol Imaging. 2014 Oct;4(4):43-57. doi: 10.4236/ami.2014.44006.
Increased physical activity and higher adherence to a Mediterranean-type diet (MeDi) have been independently associated with reduced risk of Alzheimer's disease (AD). Their association has not been investigated with the use of biomarkers. This study examines whether, among cognitively normal (NL) individuals, those who are less physically active and show lower MeDi adherence have brain biomarker abnormalities consistent with AD.
Forty-five NL individuals (age 54 ± 11, 71% women) with complete leisure time physical activity (LTA), dietary information, and cross-sectional 3D T1-weigthed MRI, C-Pittsburgh Compound B (PiB) and F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scans were examined. Voxel-wise multivariate partial least square (PLS) regression was used to examine the effects of LTA, MeDi and their interaction on brain biomarkers. Age, gender, ethnicity, education, caloric intake, BMI, family history of AD, Apolipoprotein E (APOE) genotype, presence of hypertension and insulin resistance were examined as confounds. Subjects were dichotomized into more and less physically active (LTA+ vs. LTA-; n = 21 vs. 24), and into higher vs. lower MeDi adherence groups (n = 18 vs. 27) using published scoring methods. Spatial patterns of brain biomarkers that represented the optimal association between the images and the groups were generated for all modalities using voxel-wise multivariate Partial Least Squares (PLS) regression.
Groups were comparable for clinical and neuropsychological measures. Independent effects of LTA and MeDi factors were observed in AD-vulnerable brain regions for all modalities (p < 0.001). Increased AD-burden (in particular higher A load and lower glucose metabolism) were observed in LTA- compared to LTA+ subjects, and in MeDi- as compared to MeDi+ subjects. A gradient effect was observed for all modalities so that LTA-/MeDi- subjects had the highest and LTA+/MeDi+ subjects had the lowest AD-burden (p < 0.001), although the LTA × MeDi interaction was significant only for FDG measures (p < 0.03). Adjusting for covariates did not attenuate these relationships.
Lower physical activity and MeDi adherence were associated with increased brain AD-burden among NL individuals, indicating that lifestyle factors may modulate AD risk. Studies with larger samples and longitudinal evaluations are needed to determine the predictive power of the observed associations.
增加体力活动以及更高程度地坚持地中海式饮食（MeDi）已分别与降低患阿尔茨海默病（AD）的风险相关联。尚未使用生物标志物对它们之间的关联进行研究。本研究调查在认知正常（NL）个体中，那些体力活动较少且MeDi依从性较低的人是否存在与AD一致的脑生物标志物异常。
对45名NL个体（年龄54±11岁，71%为女性）进行了检查，这些个体有完整的休闲时间体力活动（LTA）、饮食信息，以及横断面三维T1加权磁共振成像（MRI）、C-匹兹堡化合物B（PiB）和F-氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）。采用体素-wise多元偏最小二乘（PLS）回归来研究LTA、MeDi及其相互作用对脑生物标志物的影响。将年龄、性别、种族、教育程度、热量摄入、体重指数、AD家族史、载脂蛋白E（APOE）基因型、高血压和胰岛素抵抗的存在作为混杂因素进行检查。使用已发表的评分方法，将受试者分为体力活动较多和较少两组（LTA+组与LTA-组；n = 21对24），以及MeDi依从性较高和较低两组（n = 18对27）。使用体素-wise多元偏最小二乘（PLS）回归为所有模态生成代表图像与组之间最佳关联的脑生物标志物空间模式。
两组在临床和神经心理学测量方面具有可比性。在所有模态的AD易损脑区均观察到LTA和MeDi因素的独立效应（p < 0.001）。与LTA+受试者相比，LTA-受试者中观察到AD负担增加（特别是更高的A负荷和更低的葡萄糖代谢），与MeDi+受试者相比，MeDi-受试者中也是如此。在所有模态中均观察到梯度效应，使得LTA-/MeDi-受试者的AD负担最高，LTA+/MeDi+受试者的AD负担最低（p < 0.001），尽管LTA×MeDi相互作用仅在FDG测量中显著（p < 0.03）。对协变量进行调整并未减弱这些关系。
体力活动较少和MeDi依从性较低与NL个体脑AD负担增加相关，表明生活方式因素可能调节AD风险。需要进行更大样本量和纵向评估的研究来确定所观察到的关联的预测能力。
