晚发性抑郁患者随访一年的认知功能变化及静息态fMRI研究
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摘要
目的:探讨晚发性抑郁(LOD)患者随访一年的认知功能及局部脑区活动变化,并探索认知功能改变与脑区活动的相关性。方法:选取22例LOD患者(LOD组)和11例健康志愿者(对照组)为研究对象,所有受试者在入组时和随访一年后行认知功能检测,包括简易智能精神状态检查(MMSE)、蒙特利尔认知评估量表(MoCA)及成套神经心理测试(NTB),采用t检验分别对LOD组、对照组入组时和随访一年后的认知功能进行比较;同时,受试者均行静息态fMRI(rs-fMRI)检查,将预处理过的rs-fMRI数据进行低频振幅(ALFF)分析得到全脑平均ALFF(mALFF)值,利用SPM软件(rs-fMRI数据分析工具)分别对基线态LOD组与对照组的mALFF值、LOD组随访前后的mALFF值进行t检验,计算mALFF值有统计学差异的脑区,并将异常脑区的mALFF值与临床量表评分进行相关分析。结果:与入组时基线态比较,LOD组随访一年后在MMSE总分(P=0.035)、MMSE延迟回忆(P=0.020)、MoCA持续注意(P=0.011)评分减低,而NTB联想学习测验2总分(P=0.034)升高;对照组随访一年后各量表评分均无统计学差异。基线态LOD组与对照组比较,左侧眶额区包括眶部额上回、额中回mALFF值减低(t=4.1262),右侧额中回、背外侧前额叶皮层mALFF值升高(t=3.7139)。LOD患者基线态与随访一年后比较,前额叶包括双侧额上回、额中回mALFF值减低(t=5.1586)。相关分析显示基线态LOD患者左侧前额叶、颞下回,双侧枕叶、右侧中央前回mALFF值与NTB联想学习测验2总分呈正相关,而与MMSE、MoCA评分没有相关性。结论:LOD患者随访一年后存在认知功能减退及前额叶mALFF值的改变,其认知功能损害可能是部分特定脑区脑神经异常活动的表现;不同脑区尤其是前额叶脑区的功能变化可能与NTB联想学习测验2总分代表的短时记忆力有关。
Objective:To investigate the changes of cognitive function and local brain activity in patients with late-onset depression(LOD) after one-year follow-up,in order to explore the correlation between cognitive function and brain activity.Methods:22 LOD patients and 11 volunteers(normal controls,NC) were recruited in this study.All subjects underwent mini-mental state examination(MMSE),montreal cognitive assessment(MoCA),and completed Chinese version of neuropsychological test battery(NTB) both in baseline state and after one-year follow-up.And t test was used to compare cognitive function changes of the two groups respectively.Meanwhile,the resting-state BOLD-fMRI data were acquired and preprocessed,then analysis of whole brain amplitude of low frequency fluctuations(ALFF) between the two groups was performed and got the mean ALFF(mALFF) value.SPM was used to compare the mALFF values of the two groups in baseline state and the mALFF values of LOD group before and after one-year follow-up by t test,and calculate the brain regions with statistically significant different mALFF values.The correlation analysis was performed between mALFF values of abnormal brain areas and clinical scale scores.Results:Compared with the LOD group in baseline state,the total score of MMSE(P=0.035),the score of MMSE delayed recall(P=0.020) and MoCA sustained attention(P=0.011) after one-year follow-up significantly decreased,while the total score of NTB associative learning test was significantly increased(P=0.034).There was no statistically significant difference in scores of NC group after one-year follow-up.Compared with the NC group in baseline state,LOD patients showed significantly decreased mALFF values in left orbital frontal gyrus,left middle frontal gyrus(t=4.1262) and increased mALFF values in right middle frontal gyrus,dorsolateral prefrontal cortex(t=3.7139);after one-year follow-up,LOD patients showed significantly increased mALFF values in prefrontal cortex(t=5.1586).There was a positive correlation between mALFF values of LOD patients in left prefrontal cortex/inferior temporal gyrus,bilateral occipital lobe,right precentral gyrus and the total score of NTB associative learning test.However,no significant correlations were found between mALFF values and MMSE/MoCA scores.Conclusion: After one-year follow-up,LOD patients exhibited cognitive impairment and showed changes of mALFF values in prefrontal cortex.The impairment of cognitive function may result from abnormal activity in some brain regions.The functional changes in different brain regions,especially in prefrontal cortex,is possibly may be related to short-term memory indicated by total score of NTB associative learning test.
Objective:To investigate the changes of cognitive function and local brain activity in patients with late-onset depression(LOD) after one-year follow-up,in order to explore the correlation between cognitive function and brain activity.Methods:22 LOD patients and 11 volunteers(normal controls,NC) were recruited in this study.All subjects underwent mini-mental state examination(MMSE),montreal cognitive assessment(MoCA),and completed Chinese version of neuropsychological test battery(NTB) both in baseline state and after one-year follow-up.And t test was used to compare cognitive function changes of the two groups respectively.Meanwhile,the resting-state BOLD-fMRI data were acquired and preprocessed,then analysis of whole brain amplitude of low frequency fluctuations(ALFF) between the two groups was performed and got the mean ALFF(mALFF) value.SPM was used to compare the mALFF values of the two groups in baseline state and the mALFF values of LOD group before and after one-year follow-up by t test,and calculate the brain regions with statistically significant different mALFF values.The correlation analysis was performed between mALFF values of abnormal brain areas and clinical scale scores.Results:Compared with the LOD group in baseline state,the total score of MMSE(P=0.035),the score of MMSE delayed recall(P=0.020) and MoCA sustained attention(P=0.011) after one-year follow-up significantly decreased,while the total score of NTB associative learning test was significantly increased(P=0.034).There was no statistically significant difference in scores of NC group after one-year follow-up.Compared with the NC group in baseline state,LOD patients showed significantly decreased mALFF values in left orbital frontal gyrus,left middle frontal gyrus(t=4.1262) and increased mALFF values in right middle frontal gyrus,dorsolateral prefrontal cortex(t=3.7139);after one-year follow-up,LOD patients showed significantly increased mALFF values in prefrontal cortex(t=5.1586).There was a positive correlation between mALFF values of LOD patients in left prefrontal cortex/inferior temporal gyrus,bilateral occipital lobe,right precentral gyrus and the total score of NTB associative learning test.However,no significant correlations were found between mALFF values and MMSE/MoCA scores.Conclusion: After one-year follow-up,LOD patients exhibited cognitive impairment and showed changes of mALFF values in prefrontal cortex.The impairment of cognitive function may result from abnormal activity in some brain regions.The functional changes in different brain regions,especially in prefrontal cortex,is possibly may be related to short-term memory indicated by total score of NTB associative learning test.
引文
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[14] 袁勇贵,叶勤,李海林,等.老年期抑郁症与阿尔茨海默病的相关性[J].中国临床康复,2005,9(41):102-104.
[15] Wong NM,Liu HL,Lin C,et al.Loneliness in late-life depression:structural and functional connectivity during affective processing[J].Psychol Med,2016,46(12):2485-2499.
[16] Veer IM,Beckmann CF,van Tol MJ,et al.Whole brain resting-state analysis reveals decreased functional connectivity in major depression[J].Front Syst Neurosci,2010,4.pii:41.DOI:10.3389/fnsys.2010.00041.eCollection 2010.
[17] Keedwell PA,Linden DE.Integrative neuroimaging in mood disorders[J].Curr Opin Psychiatry,2013,26(1):27-32.
[18] Murray EA,Wise SP,Drevets WC.Localization of dysfunction in major depressive disorder: prefrontal cortex and amygdala[J].Biol Psychiatry,2011,69(12):e43-e54.
[19] Koenigs M,Grafman J.The functional neuroanatomy of depression:distinct roles for ventromedial and dorsolateral prefrontal cortex[J].Behav Brain Res,2009,201(2):239-243.
[20] Farb NA,Anderson AK,Bloch RT,et al.Mood-linked responses in medial prefrontal cortex predict relapse in patients with recurrent unipolar depression[J].Biol Psychiatry,2011,70(4):366-372.
[21] Zhou M,Hu X,Lu L,et al.Intrinsic cerebral activity at resting state in adults with major depressivedisorder:A meta-analysis[J].Prog Neuropsychopharmacol Biol Psychiatry,2017,75:157-164.DOI:10.1016/j.pnpbp.2017.02.001.Epub 2017 Feb 4.
[22] Yue Y,Jia X,Hou Z,et al.Frequency-dependent amplitude alterations of resting-state spontaneous fluctuations in late-onset depression[J].Biomed Res Int,2015,2015:505479.DOI:10.1155/2015/505479.Epub 2015 Feb 1.
[23] Guo WB,Liu F,Xun GL,et al.Reversal alterations of amplitude of low-frequency fluctuations in early and late onset,first-episode,drug-naive depression[J].Prog Neuropsychopharmacol Biol Psychiatry,2013,40:153-159.DOI:10.1016/j.pnpbp.2012.08.014.Epub 2012 Aug 31.
[24] 阎锐,姚志剑,卢青,等.抑郁症首次发病与复发患者静息态功能磁共振低频振幅比率的差异[J].临床精神医学杂志,2013,23(03):145-148.
[25] Grimm S,Beck J,Schuepbach D,et al.Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment:an fMRI study in severe major depressive disorder[J].Biol Psychiatry,2008,63(4):369-376.
[26] 缪光胜.抑郁症患者脑白质纤维的各向异性变化[J].放射学实践,2011,26(3):275-277.
[27] 吴明祥,陈宇,凌人男,等.脑卒中后抑郁症患者的海马形态分析[J].放射学实践,2014,29(5):521-524.
[2] Barnes DE,Alexopoulos GS,Lopez OL,et al.Depressive symptoms,vascular disease,and mild cognitive impairment: findings from the Cardiovascular Health Study[J].Arch Gen Psychiatry,2006,63(3):273-279.
[3] Bhalla RK,Butters MA,Becker JT,et al.Patterns of mild cognitive impairment after treatment of depression in the elderly[J].Am J Geriatr Psychiatry,2009,17(4):308-316.
[4] 杨宏伟,张蕴.晚发性抑郁认知功能的研究进展[J].医学综述,2012,18(14):2219-2222.
[5] Barnes DE,Yaffe K,Byers AL,et al.Midlife vs late-life depressive symptoms and risk of dementia:differential effects for Alzheimer disease and vascular dementia[J].Arch Gen Psychiatry,2012,69(5):493-498.
[6] 胡振波,邵静.老年抑郁症的临床症状与治疗[J].中国中医药现代远程教育,2011,9(01):102-103.
[7] Disabato BM,Sheline YI.Biological basis of late life depression[J].Curr Psychiatry Rep,2012,14(4):273-279.
[8] Mah L,Anderson ND,Verhoeff N,et al.Negative Emotional verbal memory biases in mild cognitive impairment and late-onset depression[J].Am J Geriatr Psychiatry,2017,25(10):1160-1170.
[9] Wong MM,Chan CF,Li SW,et al.Six-month follow-up of cognitive impairment and depressive symptoms in late-onset depression[J].East Asian Arch Psychiatry,2015,25(4):146-149.
[10] Yin Y,Wang Z,Zhang Z,et al.Aberrant topographical organization of the default mode network underlying the cognitive impairment of remitted late-onset depression[J].Neurosci Lett,2016,629:26-32.DOI:10.1016/j.neulet.2016.06.048. Epub 2016 Jun 27.
[11] Yin Y,He X,Xu M,et al.Structural and functional connectivity of default mode network underlying the cognitive impairment in late-onset depression[J].Sci Rep,2016,6:37617.DOI:10.1038/srep37617.
[12] Vinkers DJ,van der Mast RC.Temporal course of depressive symptoms during the development of Alzheimer disease:blowing hot and cold over depression and cognitive impairment[J].Neurology,2011,76(17):1531-1532.
[13] Chung JK,Plitman E,Nakajima S,et al.Cortical amyloid beta deposition and current depressive symptoms in Alzheimer disease and mild cognitive impairment[J].J Geriatr Psychiatry Neurol,2016,29(3):149-159.
[14] 袁勇贵,叶勤,李海林,等.老年期抑郁症与阿尔茨海默病的相关性[J].中国临床康复,2005,9(41):102-104.
[15] Wong NM,Liu HL,Lin C,et al.Loneliness in late-life depression:structural and functional connectivity during affective processing[J].Psychol Med,2016,46(12):2485-2499.
[16] Veer IM,Beckmann CF,van Tol MJ,et al.Whole brain resting-state analysis reveals decreased functional connectivity in major depression[J].Front Syst Neurosci,2010,4.pii:41.DOI:10.3389/fnsys.2010.00041.eCollection 2010.
[17] Keedwell PA,Linden DE.Integrative neuroimaging in mood disorders[J].Curr Opin Psychiatry,2013,26(1):27-32.
[18] Murray EA,Wise SP,Drevets WC.Localization of dysfunction in major depressive disorder: prefrontal cortex and amygdala[J].Biol Psychiatry,2011,69(12):e43-e54.
[19] Koenigs M,Grafman J.The functional neuroanatomy of depression:distinct roles for ventromedial and dorsolateral prefrontal cortex[J].Behav Brain Res,2009,201(2):239-243.
[20] Farb NA,Anderson AK,Bloch RT,et al.Mood-linked responses in medial prefrontal cortex predict relapse in patients with recurrent unipolar depression[J].Biol Psychiatry,2011,70(4):366-372.
[21] Zhou M,Hu X,Lu L,et al.Intrinsic cerebral activity at resting state in adults with major depressivedisorder:A meta-analysis[J].Prog Neuropsychopharmacol Biol Psychiatry,2017,75:157-164.DOI:10.1016/j.pnpbp.2017.02.001.Epub 2017 Feb 4.
[22] Yue Y,Jia X,Hou Z,et al.Frequency-dependent amplitude alterations of resting-state spontaneous fluctuations in late-onset depression[J].Biomed Res Int,2015,2015:505479.DOI:10.1155/2015/505479.Epub 2015 Feb 1.
[23] Guo WB,Liu F,Xun GL,et al.Reversal alterations of amplitude of low-frequency fluctuations in early and late onset,first-episode,drug-naive depression[J].Prog Neuropsychopharmacol Biol Psychiatry,2013,40:153-159.DOI:10.1016/j.pnpbp.2012.08.014.Epub 2012 Aug 31.
[24] 阎锐,姚志剑,卢青,等.抑郁症首次发病与复发患者静息态功能磁共振低频振幅比率的差异[J].临床精神医学杂志,2013,23(03):145-148.
[25] Grimm S,Beck J,Schuepbach D,et al.Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment:an fMRI study in severe major depressive disorder[J].Biol Psychiatry,2008,63(4):369-376.
[26] 缪光胜.抑郁症患者脑白质纤维的各向异性变化[J].放射学实践,2011,26(3):275-277.
[27] 吴明祥,陈宇,凌人男,等.脑卒中后抑郁症患者的海马形态分析[J].放射学实践,2014,29(5):521-524.