Soldan Anja, Pettigrew Corinne, Lu Yi, Wang Mei-Cheng, Selnes Ola, Albert Marilyn, Brown Timothy, Ratnanather J Tilak, Younes Laurent, Miller Michael I
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Hum Brain Mapp. 2015 Jul;36(7):2826-41. doi: 10.1002/hbm.22810. Epub 2015 Apr 16.
This study evaluated the utility of baseline and longitudinal magnetic resonance imaging (MRI) measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the time to onset of clinical symptoms associated with mild cognitive impairment (MCI). Furthermore, we examined whether the relationship between MRI measures and clinical symptom onset was modified by apolipoprotein E (ApoE) genotype and level of cognitive reserve (CR). MRI scans and measures of CR were obtained at baseline from 245 participants who had been followed for up to 18 years (mean follow-up 11 years). A composite score based on reading, vocabulary, and years of education was used as an index of CR. Cox regression models showed that lower baseline volume of the right hippocampus and smaller baseline thickness of the right entorhinal cortex predicted the time to symptom onset independently of CR and ApoE-ɛ4 genotype, which also predicted the onset of symptoms. The atrophy rates of bilateral entorhinal cortex and amygdala volumes were also associated with time to symptom onset, independent of CR, ApoE genotype, and baseline volume. Only one measure, the left entorhinal cortex baseline volume, interacted with CR, such that smaller volumes predicted symptom onset only in individuals with lower CR. These results suggest that MRI measures of medial temporal atrophy, ApoE-ɛ4 genotype, and the protective effects of higher CR all predict the time to onset of symptoms associated with MCI in a largely independent, additive manner during the preclinical phase of Alzheimer's disease.
本研究评估了参与者认知正常且大多处于中年（平均年龄57岁）时收集的内侧颞叶脑区的基线和纵向磁共振成像（MRI）测量指标，以预测与轻度认知障碍（MCI）相关的临床症状出现的时间。此外，我们还研究了MRI测量指标与临床症状出现之间的关系是否因载脂蛋白E（ApoE）基因型和认知储备（CR）水平而改变。在基线时，对245名参与者进行了MRI扫描并测量了CR，这些参与者被随访了长达18年（平均随访11年）。基于阅读、词汇和受教育年限的综合评分被用作CR的指标。Cox回归模型显示，右侧海马体的较低基线体积和右侧内嗅皮质的较小基线厚度可独立于CR和ApoE-ɛ4基因型预测症状出现的时间，而ApoE-ɛ4基因型也可预测症状的出现。双侧内嗅皮质的萎缩率和杏仁核体积也与症状出现的时间相关，独立于CR、ApoE基因型和基线体积。只有一个测量指标，即左侧内嗅皮质基线体积，与CR相互作用，使得较小的体积仅在CR较低的个体中预测症状出现。这些结果表明，内侧颞叶萎缩的MRI测量指标、ApoE-ɛ4基因型以及较高CR的保护作用，在阿尔茨海默病临床前期均以基本独立、累加的方式预测与MCI相关的症状出现时间。
