台灣老年人磁核造影影像預測認知功能下降之研究

蔡秉寰

doi:10.6342/NTU201601905

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台湾老年人磁核造影影像预测认知功能下降之研究

Magnetic Resonance Imaging Measures Predict Cognitive Decline in Taiwanese Elderly

蔡秉寰 , 硕士　　导师：程蕴菁　　共同指导教授：洪弘

英文 DOI： 10.6342/NTU201601905

磁核造影；认知功能下降；老年人； magnetic resonance imaging ； cognitive decline ； elderly

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摘要 │ 参考文献 (36) │ 国际计量

摘要〈TOP〉

研究背景: 台湾老年人口比例逐渐增加，因此老年人相关议题是首当其冲(例如:失智症)。脑中结构的细微变化在失智症发生的初期即可以磁核造影侦测到。过去研究主要以探讨脑中特定的区块，显少探讨这些区块以外的脑区。因此，本研究旨在探讨磁核造影影像与预测认知功能下降之关联。

材料与方法: 本研究为世代追踪研究，於基线 (2011&not;-2013)至两年後追踪 (2013-2015)，共招募316位台大医院老年健康检查之65岁以上长者。本研究的结果为测量基线到追踪之认知功能(包括整体与特定范畴认知功能，例如: 记忆、语言流畅、执行功能和专注力)下降。於基线期间进行磁核造影，总共测量114个脑体积与68个脑厚度变项。利用因素分析萃取认知功能因子。切片逆回归方式将磁核造影影像降维成磁核造影因子。以多变项线性与逻辑式回归模型评估磁核造影影像与认知功能下降之关联性，并针对重要混淆因子进行分层分析，例如:年龄 (<75岁、≧75岁)、性别与载脂蛋白E (APOE ε4)状态。

结果: 本研究经因素分析後得到四个认知功能范畴因子 (记忆、语言流畅、执行功能和专注)。每增加一单位MRI因素1 (包括：边缘系统、 脑岛与前额叶区块)可减少整体性认知功能下降 (回归系数 = 0.002)；每增加一单位MRI因素3 (包括：边缘系统与前额叶区块)可减少整体性认知功能下降 (调整胜算比= 0.75)。每增加一单位MRI因素3 (包括：边缘系统、前额叶与颞叶区块)可预测记忆功能下降 (回归系数 = -0.34，调整胜算比 =1.79)；每增加一单位MRI因素2 (包括：顶叶、前额叶与颞叶区块)可预测记忆功能下降 (调整胜算比= 1.59)。每增加一单位MRI因素1 (包括：边缘系统与颞叶区块)可预测语言流畅功能下降 (回归系数 = -0.20)；然而，每增加一单位MRI因素3 (包括：前额叶与顶叶区块)可减少语言流畅功能下降 (回归系数 =0.18，调整胜算比 =0.58)。每增加一单位MRI因素1 (包括：前额叶、与颞叶区块)可预测执行功能下降(调整胜算比 =0.65)。每增加一单位MRI因素1 (包括:伏隔核、颞叶与前额叶区块)可减少执行功能下降 (回归系数 =0.29，调整胜算比 =0.49)；然而，每增加一单位MRI因素3 (包括：第五脑室、颞叶与前额叶区块)可预测专注功能下降 (回归系数 =-0.11)。
结论: 本研究是第一篇以无假设的方法来辨认磁核造影生物标记。本研究大部分的发现与先前研究相同 (例如：前额叶、颞叶和边缘系通区块)，除了在边缘系统、伏隔核、脑室、距状沟与眼眶额叶皮质区块目前尚未在未失智老年人中发现与认知下降有关。这些相关发现在较老的族群 (年龄≧75岁)、女性与带有APOEε4基因者依旧存在。因此，本研究可早期侦测与预防老年人认知功能缺损情况。

并列摘要〈TOP〉

Background: The proportion of elders in Taiwan increase rapidly and thus age-related health issues (e.g., dementia) become an important topic in the elderly. Brain structural changes begin at the early stage of dementia, and magnetic resonance imaging (MRI) technique can identify these subtle changes. Previous studies using MRI on brain regions of interest, and thus the remaining regions are less explored. Therefore, this study aims to explore the association between MRI measures and cognitive decline in Taiwanese elders.

Methods: This cohort study recruited 316 participants aged 65 or older from the annual Elderly Health Checkup Program at National Taiwan University Hospital from 2011 to 2013 (baseline) and followed up from 2013 to 2015. The outcome of this study is global and domain-specific (memory, verbal fluency, executive function and attention) cognitive decline from baseline to follow-up. MRI scans were performed at baseline with a total of 114 volume variables and 68 thickness variables. Factor analysis was performed to identify cognitive factors. Slice inverse regression was performed for dimension reduction of MRI variables to identify MRI factors. Multivariable linear and logistic regressions were used to assess the association between MRI measures and cognitive decline. Stratified analyses were performed by important confounders, which included age groups (<75 and ≧75 years old), sex, and apolipoprotein E (APOE) ε4 status.
Results: Four cognitive factors (memory, verbal fluency, executive function and attention factors) were identified by factor analysis. One unit increase in MRI factors 1 (including limbic, insula and frontal regions) protected against the decline of global cognition (MoCA-T, β= 0.002); one unit increase in MRI factor 3 (including limbic and frontal regions) showed similar finding [MoCA-T, adjusted odds ratio (AOR) = 0.75]. One unit increase in MRI factors 3 (including limbic, frontal and temporal regions) was associated with decline of memory factor (β= -0.34, AOR = 1.79); one unit increase in MRI factor 2 (including parietal, frontal and temporal regions) showed similar finding (AOR = 1.59). One unit increase in MRI factor 1 (including limbic and temporal regions) was associated with the decline of verbal fluency factor (β= -0.20). While one unit increase in MRI factor 3 (including frontal and temporal regions) protected against the decline of verbal fluency factor (β= 0.18, AOR = 0.58). One unit increase in MRI factors 1 (including frontal and temporal regions) was associated with the decline of executive function factor (AOR = 0.65). One unit increase in MRI factors 1 (including accumbens, temporal and frontal regions) protected against the decline of attention factor (β= 0.29, AOR = 0.49), while one unit increase in MRI factors 3 (including 5th ventricle, frontal and temporal regions) was associated with decline of attention factor (β= -0.11).

Conclusion: This study used hypothesis-free approach to identify MRI markers. Most of our findings are consist with previous studies (e.g., frontal, temporal, and limbic regions) except limbic, accumbens, ventricles, pericalcarine and pars orbitalis regions have not been related to early cognitive decline in non-demented elderly previously. Finding remain significant especially in older group (ages≧75), women, and APOE ε4 carriers. Our findings are useful for early detection and prevention of dementia in the elderly.

参考文献 ( 36 ) 〈TOP〉

Baldo J. V., Schwartz S., Wilkins D. and Dronkers N. F. (2006). "Role of frontal versus temporal cortex in verbal fluency as revealed by voxel-based lesion symptom mapping." Journal of the International Neuropsychological Society 12(6): 896-900.
连结：
Baldo J. V., Shimamura A. P., Delis D. C., Kramer J. and Kaplan E. (2001). "Verbal and design fluency in patients with frontal lobe lesions." Journal of the International Neuropsychological Society 7(5): 586-596.
连结：
Barnes J., Ridgway G. R., Bartlett J., Henley S. M. D., Lehmann M., Hobbs N., Clarkson M. J., MacManus D. G., Ourselin S. and Fox N. C. (2010). "Head size, age and gender adjustment in MRI studies: a necessary nuisance?" NeuroImage 53(4): 1244-1255.
连结：
Barnes L. L., Wilson R. S., Bienias J. L., Schneider J. A., Evans D. A. and Bennett D. A. (2005). "Sex differences in the clinical manifestations of Alzheimer disease pathology." Archives of General Psychiatry 62(6): 685-691.
连结：
Bozzali M., Filippi M., Magnani G., Cercignani M., Franceschi M., Schiatti E., Castiglioni S., Mossini R., Falautano M., Scotti G., Comi G. and Falini A. (2006). "The contribution of voxel-based morphometry in staging patients with mild cognitive impairment." Neurology 67(3): 453-460.
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