阿尔茨海默病中高血压对大脑皮层厚度和认知功能的影响
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摘要
阿尔茨海默病是一种以大脑皮层厚度萎缩和认知功能下降为特征的进行性神经退化痴呆症。轻度认知障碍是介于正常衰老与阿尔茨海默病之间的一种过渡阶段,通过分析轻度认知障碍患者和阿尔茨海默病患者的大脑皮层厚度变化,我们可以了解疾病的发生发展原理,为临床早期诊断和预防提供帮助。高血压作为阿尔茨海默病的风险性因素,可引起大脑萎缩,加速认知功能的缺失。本文主要研究轻度认知障碍患者的皮层厚度萎缩和阿尔茨海默病患者中高血压人群与非高血压人群的皮层厚度差异和认知功能差异。
首先,基于组群的大脑皮层厚度纵向研究,分析阿尔茨海默病和轻度认知障碍患者大脑皮层厚度随着病程发展的变化模式和发生病变的大脑皮层的区域,我们发现随着病程的发展,大脑皮层厚度是逐渐萎缩变薄,首先发生病变而变薄的脑区主要集中在默认网络的核心区域,而这些区域也就是跟认知和记忆及其相关的区域,而后向默认网络的其他脑区扩散,最后发展到全脑萎缩。
其次,在阿尔茨海默病患者中,我们把患者是否是高血压作为一个重要因素进行研究,高血压人群更容易转变为阿尔茨海默病患者。通过对高血压人群与非高血压人群的大脑皮层厚度比较,我们发现在颞叶区域,高血压人群皮层显著变薄。
最后,通过对阿尔茨海默病患者中高血压人群与非高血压人群的行为认知评分比较,我们发高血压人群的认知功能有严重缺失。这就促使我们认识到在治疗阿尔茨海默病患者中,把降低病人的血压作为一个关键的手段进行研究。
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive impairment of cognitive function and atrophy of cerebral cortex.Mild cognitive impairment is a transitional stage between normal aging and Alzheimer's disease, With the analysis of cortical thickness changes in patients with mild cognitive impairment,we could understand the development of the disease and help us prevent the disease.This paper mainly studies cortical thickness atrophy in patients with mild cognitive impairment and the cortical thickness and cognitive function differences between people with hypertension and without hypertension.
First, based on the population, we investigated longitudinal changes of the cortical thickness of AD and MCI patients. We found that the regions that have atrophies are mainly those in default mode network (DMN) which is considered to be associated with the cognitive function and memory.
Secondly,when we study Alzheimer's disease,hypertension is considered to be an important fator.With the comparison of cortical thickness in the hypertensive population and non-hypertensive population,we found that in the temporal lobe region,the cortical thickness of hypertensive population is significantly thinner.
Finally,with the comparison of cognitive scores between Alzheimer's disease with hypertension and without hypertension,we found that the cognitive function of the hypertensive population has serious deficiencies. This prompt us to realize that reduce the patients" blood pressure is very important in the treatment of Alzheimer's disease.
首先,基于组群的大脑皮层厚度纵向研究,分析阿尔茨海默病和轻度认知障碍患者大脑皮层厚度随着病程发展的变化模式和发生病变的大脑皮层的区域,我们发现随着病程的发展,大脑皮层厚度是逐渐萎缩变薄,首先发生病变而变薄的脑区主要集中在默认网络的核心区域,而这些区域也就是跟认知和记忆及其相关的区域,而后向默认网络的其他脑区扩散,最后发展到全脑萎缩。
其次,在阿尔茨海默病患者中,我们把患者是否是高血压作为一个重要因素进行研究,高血压人群更容易转变为阿尔茨海默病患者。通过对高血压人群与非高血压人群的大脑皮层厚度比较,我们发现在颞叶区域,高血压人群皮层显著变薄。
最后,通过对阿尔茨海默病患者中高血压人群与非高血压人群的行为认知评分比较,我们发高血压人群的认知功能有严重缺失。这就促使我们认识到在治疗阿尔茨海默病患者中,把降低病人的血压作为一个关键的手段进行研究。
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive impairment of cognitive function and atrophy of cerebral cortex.Mild cognitive impairment is a transitional stage between normal aging and Alzheimer's disease, With the analysis of cortical thickness changes in patients with mild cognitive impairment,we could understand the development of the disease and help us prevent the disease.This paper mainly studies cortical thickness atrophy in patients with mild cognitive impairment and the cortical thickness and cognitive function differences between people with hypertension and without hypertension.
First, based on the population, we investigated longitudinal changes of the cortical thickness of AD and MCI patients. We found that the regions that have atrophies are mainly those in default mode network (DMN) which is considered to be associated with the cognitive function and memory.
Secondly,when we study Alzheimer's disease,hypertension is considered to be an important fator.With the comparison of cortical thickness in the hypertensive population and non-hypertensive population,we found that in the temporal lobe region,the cortical thickness of hypertensive population is significantly thinner.
Finally,with the comparison of cognitive scores between Alzheimer's disease with hypertension and without hypertension,we found that the cognitive function of the hypertensive population has serious deficiencies. This prompt us to realize that reduce the patients" blood pressure is very important in the treatment of Alzheimer's disease.
引文
[1]孙久荣.脑科学导论.北京大学出版社.2001.
[2]杨雄里.脑科学的现代进展.上海科技教育出版社.1998.
[3]李振平.临床中枢神经解剖学.北京科学出版社.2003.
[4]李联忠.戴建平,赵斌.颅脑MR I诊断.北京人民卫生出版社.2001.
[5]Thompson, P.M. and A.W. Toga, A framework for computational anatomy. Computing and Visualization in Science,2002.5(1):p.13-34.
[6]Ascoli, G.A., Progress and perspectives in computational neuroanatomy. The anatomical record,1999.257(6):p.195-207.
[7]MacDonald, D., et al., Automated 3-D extraction of inner and outer surfaces of cerebral cortex from MRI. NeuroImage,2000.12(3):p.340.
[8]Fischl, B. and A.M. Dale, Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences,2000.97(20): p.11050-11055.
[9]Jones, S.E., B.R. Buchbinder, and I. Aharon, Three-dimensional mapping of cortical thickness using Laplace's Equation. Human brain mapping,2000.11(1):p.12-32.
[10]Sowell, E.R., et al., Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age. Cerebral Cortex,2007.17(7):p.1550-1560.
[11]Goldman, A.L., et al., Widespread reductions of cortical thickness in schizophrenia and spectrum disorders and evidence of heritability. Archives of general psychiatry,2009.66(5):p. 467.
[12]Jiang, J., et al., Thick visual cortex in the early blind. The Journal of Neuroscience,2009. 29(7):p.2205-2211.
[13]He, Y., Z.J. Chen, and A.C. Evans, Small-world anatomical networks in the human brain revealed by cortical thickness from MRI. Cerebral cortex,2007.17(10):p.2407-2419.
[14]FRACKOWIAK, R., A Voxei-Based Method for the Statistical Analysis of Gray and White Matter Density Applied to Schizophrenia. Neuroimage,1995.2:p.244-252.
[15]Ashburner, J. and K.J. Friston, Voxel-based morphometry-the methods. Neuroimage,2000. 11(6):p.805-821.
[16]Good, C.D., et al. A voxel-based morphometric study of ageing in 465 normal adult human brains, in Biomedical Imaging,2002.5th IEEE EMBS International Summer School on.2002. 14(1):p.21-36.
[17]Boddaert, N., et al., Superior temporal sulcus anatomical abnormalities in childhood autism:a voxel-based morphometry MRI study. Neuroimage,2004.23(1):p.364.
[18]Lyoo, I.K., et al., Frontal lobe gray matter density decreases in bipolar I disorder. Biological psychiatry,2004.55(6):p.648.
[19]Draganski, B., et al., Neuroplasticity:changes in grey matter induced by training. Nature. 2004.427(6972):p.311-312.
[20]Lenroot, R.K. and J.N. Giedd, Brain development in children and adolescents:insights from anatomical magnetic resonance imaging. Neuroscience and biobehavioral reviews,2006. 30(6):p.718-729.
[21]Anstey, K. and J. Mailer, The role of volumetric MRI in understanding mild cognitive impairment and similar classifications. Aging & Mental Health,2003.7(4):p.238-250.
[22]Wiegand, L.C., et al., An in vivo MRI study of prefrontal cortical complexity in first-episode psychosis. The American journal of psychiatry,2005.162(1):p.65.
[23]Chung, M.K., et al., Weighted fourier series representation and its application to quantifying the amount of gray matter. Medical Imaging, IEEE Transactions on,2007.26(4):p.566-581.
[24]Kuperberg, G.R., et al., Regionally localized thinning of the cerebral cortex in schizophrenia. Archives of general psychiatry,2003.60(9):p.878.
[25]Narr, K.L., et al., Mapping cortical thickness and gray matter concentration in first episode schizophrenia. Cerebral Cortex,2005.15(6):p.708-719.
[26]Genovese, C.R., N.A. Lazar, and T. Nichols, Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage,2002.15(4):p.870-878.
[27]Thompson, P.M., et al., Genetic influences on brain structure. Nature neuroscience,2001. 4(12):p.1253-1258.
[28]Shaw, P., et al., Intellectual ability and cortical development in children and adolescents. Nature,2006.440(7084):p.676-679.
[29]Petersen, R.C., et al., Mild cognitive impairment:clinical characterization and outcome. Archives of neurology,1999.56(3):p.303.
[30]Dickerson, B.C., et al., Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area. Neurobiology of aging,2009.30(3):p. 432-440.
[31]Wimo, A., et al., The magnitude of dementia occurrence in the world. Alzheimer Disease & Associated Disorders,2003.17(2):p.63-67.
[32]Salerno, J.A., et al., Brain atrophy in hypertension. A volumetric magnetic resonance imaging study. Hypertension,1992.20(3):p.340-348.
[33]Dozono, K., et al., An autopsy study of the incidence of lacunes in relation to age, hypertension, and arteriosclerosis. Stroke,1991.22(8):p.993-996.
[34]Vagaonescu, T.D., et al., Hypertensive cardiovascular damage in patients with primary autonomic failure. The Lancet,2000.355(9205):p.725-726.
[35]Nagai, M., et al., Ambulatory blood pressure as an independent determinant of brain atrophy and cognitive function in elderly hypertension. Journal of hypertension,2008.26(8):p. 1636-1641.
[36]Sperling, R.A., et al., Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's and Dementia,2011.7(3):p. 280-292.
[37]Raz, N., et al., Regional brain changes in aging healthy adults:general trends, individual differences and modifiers. Cerebral cortex,2005.15(11):p.1676-1689.
[38]Crum, R.M., et al., Population-based norms for the Mini-Mental State Examination by age and educational level. JOURNAL-AMERICAN MEDICAL ASSOCIATION.1993.269:p. 2386-2386.
[39]Pfeffer, R., et al., Measurement of functional activities in older adults in the community. Journal of gerontology,1982.37(3):p.323-329.
[40]Rosen, W.G., R.C. Mohs, and K.L. Davis, A new rating scale for Alzheimer's disease. The American journal of psychiatry,1984.12(8):p.10-15.
[2]杨雄里.脑科学的现代进展.上海科技教育出版社.1998.
[3]李振平.临床中枢神经解剖学.北京科学出版社.2003.
[4]李联忠.戴建平,赵斌.颅脑MR I诊断.北京人民卫生出版社.2001.
[5]Thompson, P.M. and A.W. Toga, A framework for computational anatomy. Computing and Visualization in Science,2002.5(1):p.13-34.
[6]Ascoli, G.A., Progress and perspectives in computational neuroanatomy. The anatomical record,1999.257(6):p.195-207.
[7]MacDonald, D., et al., Automated 3-D extraction of inner and outer surfaces of cerebral cortex from MRI. NeuroImage,2000.12(3):p.340.
[8]Fischl, B. and A.M. Dale, Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences,2000.97(20): p.11050-11055.
[9]Jones, S.E., B.R. Buchbinder, and I. Aharon, Three-dimensional mapping of cortical thickness using Laplace's Equation. Human brain mapping,2000.11(1):p.12-32.
[10]Sowell, E.R., et al., Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age. Cerebral Cortex,2007.17(7):p.1550-1560.
[11]Goldman, A.L., et al., Widespread reductions of cortical thickness in schizophrenia and spectrum disorders and evidence of heritability. Archives of general psychiatry,2009.66(5):p. 467.
[12]Jiang, J., et al., Thick visual cortex in the early blind. The Journal of Neuroscience,2009. 29(7):p.2205-2211.
[13]He, Y., Z.J. Chen, and A.C. Evans, Small-world anatomical networks in the human brain revealed by cortical thickness from MRI. Cerebral cortex,2007.17(10):p.2407-2419.
[14]FRACKOWIAK, R., A Voxei-Based Method for the Statistical Analysis of Gray and White Matter Density Applied to Schizophrenia. Neuroimage,1995.2:p.244-252.
[15]Ashburner, J. and K.J. Friston, Voxel-based morphometry-the methods. Neuroimage,2000. 11(6):p.805-821.
[16]Good, C.D., et al. A voxel-based morphometric study of ageing in 465 normal adult human brains, in Biomedical Imaging,2002.5th IEEE EMBS International Summer School on.2002. 14(1):p.21-36.
[17]Boddaert, N., et al., Superior temporal sulcus anatomical abnormalities in childhood autism:a voxel-based morphometry MRI study. Neuroimage,2004.23(1):p.364.
[18]Lyoo, I.K., et al., Frontal lobe gray matter density decreases in bipolar I disorder. Biological psychiatry,2004.55(6):p.648.
[19]Draganski, B., et al., Neuroplasticity:changes in grey matter induced by training. Nature. 2004.427(6972):p.311-312.
[20]Lenroot, R.K. and J.N. Giedd, Brain development in children and adolescents:insights from anatomical magnetic resonance imaging. Neuroscience and biobehavioral reviews,2006. 30(6):p.718-729.
[21]Anstey, K. and J. Mailer, The role of volumetric MRI in understanding mild cognitive impairment and similar classifications. Aging & Mental Health,2003.7(4):p.238-250.
[22]Wiegand, L.C., et al., An in vivo MRI study of prefrontal cortical complexity in first-episode psychosis. The American journal of psychiatry,2005.162(1):p.65.
[23]Chung, M.K., et al., Weighted fourier series representation and its application to quantifying the amount of gray matter. Medical Imaging, IEEE Transactions on,2007.26(4):p.566-581.
[24]Kuperberg, G.R., et al., Regionally localized thinning of the cerebral cortex in schizophrenia. Archives of general psychiatry,2003.60(9):p.878.
[25]Narr, K.L., et al., Mapping cortical thickness and gray matter concentration in first episode schizophrenia. Cerebral Cortex,2005.15(6):p.708-719.
[26]Genovese, C.R., N.A. Lazar, and T. Nichols, Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage,2002.15(4):p.870-878.
[27]Thompson, P.M., et al., Genetic influences on brain structure. Nature neuroscience,2001. 4(12):p.1253-1258.
[28]Shaw, P., et al., Intellectual ability and cortical development in children and adolescents. Nature,2006.440(7084):p.676-679.
[29]Petersen, R.C., et al., Mild cognitive impairment:clinical characterization and outcome. Archives of neurology,1999.56(3):p.303.
[30]Dickerson, B.C., et al., Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area. Neurobiology of aging,2009.30(3):p. 432-440.
[31]Wimo, A., et al., The magnitude of dementia occurrence in the world. Alzheimer Disease & Associated Disorders,2003.17(2):p.63-67.
[32]Salerno, J.A., et al., Brain atrophy in hypertension. A volumetric magnetic resonance imaging study. Hypertension,1992.20(3):p.340-348.
[33]Dozono, K., et al., An autopsy study of the incidence of lacunes in relation to age, hypertension, and arteriosclerosis. Stroke,1991.22(8):p.993-996.
[34]Vagaonescu, T.D., et al., Hypertensive cardiovascular damage in patients with primary autonomic failure. The Lancet,2000.355(9205):p.725-726.
[35]Nagai, M., et al., Ambulatory blood pressure as an independent determinant of brain atrophy and cognitive function in elderly hypertension. Journal of hypertension,2008.26(8):p. 1636-1641.
[36]Sperling, R.A., et al., Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's and Dementia,2011.7(3):p. 280-292.
[37]Raz, N., et al., Regional brain changes in aging healthy adults:general trends, individual differences and modifiers. Cerebral cortex,2005.15(11):p.1676-1689.
[38]Crum, R.M., et al., Population-based norms for the Mini-Mental State Examination by age and educational level. JOURNAL-AMERICAN MEDICAL ASSOCIATION.1993.269:p. 2386-2386.
[39]Pfeffer, R., et al., Measurement of functional activities in older adults in the community. Journal of gerontology,1982.37(3):p.323-329.
[40]Rosen, W.G., R.C. Mohs, and K.L. Davis, A new rating scale for Alzheimer's disease. The American journal of psychiatry,1984.12(8):p.10-15.
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