轻度认知障碍和阿尔茨海默病患者海马及海马旁回厚度变化研究

目的 评价高分辨影像学测定海马厚度对轻度认知功能障碍(mild cognitive impairment,MCI)和阿尔茨海默病 (Alzheimer's disease,AD)的诊断价值.方法 应用西门子3.0T磁共振采集25例 MCI患者,25例AD患者及25例正常对照的高分辨图像,用FreeSurfer软件测量3组海马及海马旁回皮质厚度,后用SPSS 17.0比较3组之间皮质厚度的差异.结果 MCI组[左侧(2.52±0.31) mm,右侧(2.44±0.43) mm],AD组[左侧(2.41±0.39) mm,右侧(2.37±0.38) mm]分别与对照组两侧海马,以及MCI组[左侧(2.23±0.51) mm,右侧(2.19±0.37) mm],AD组[左侧(2.11±0.41) mm,右侧(2.03±0.67) mm]海马旁回皮质厚度均存在显著的统计学差异,且AD组比MCI组在海马(左侧0.11 mm,右侧0.07 mm)及海马旁(左侧0.12 mm,右侧0.16 mm)均值上有更明显的萎缩.结论 海马及海马旁回皮质厚度与认知功能有一定相关,且厚度萎缩情况对疾病的阶段性发展具有一定的诊断意义.     

中国汉族成人额叶体积的高分辨率MRI测量

目的 测量中国汉族正常成人大脑额叶体积,为建立中国成人数字标准脑提供基础数据.方法 采用全国多中心临床研究形式,选取18～70岁健康志愿者200名,按照年龄18～30、31～40、41～50、51～60、61～70岁进行分组,每组男、女各20名.所有受试者均行3D磁化强度预备梯度回波序列T1WI采集额叶体积,通过人工勾画ROI法分别测量志愿者左、右侧额叶体积,并对测量数据进行统计学分析.男、女性别间比较采用独立样本t检验;左、右侧别间比较采用配对样本t检验;年龄与额叶体积进行相关与回归分析.结果 200名志愿者大脑额叶总体积为(563±73)cm3.100名男性左、右侧额叶体积值分别为(288±42)、(292±41)cm3;100名女性左、右侧额叶体积值分别为(273±30)、(274±30)cm3.大脑额叶总体积男、女性别间差异有统计学意义(t=3.334,P<0.05).男性左、右侧额叶体积差异有统计学意义(t=-3.09,P<0.05),女性左、右侧额叶体积差异无统计学意义(t=-1.304,P>0.05).男性及女性大脑额叶总体积均与年龄呈负相关(r值分别为-0.586、-0.498,P值均<0.01).结论 健康国人男性额叶总体积大于女性.男性右侧额叶体积大于左侧,而女性双侧额叶体积差异无统计学意义.随着年龄的增长,男性及女性的额叶总体积均呈现逐渐缩小的趋势,男性额叶缩小的趋势比女性明显.     

额颞叶变性亚型与阿尔茨海默病的脑灰质萎缩模式的结构MRI研究

目的 比较分析额颞叶变性(FTLD)的两个亚型,即行为变异型额颞叶痴呆(bvFTD)和原发性进行性失语(PPA),与阿尔茨海默病(AD)的脑灰质萎缩模式,为早期诊断和鉴别诊断提供客观的支持依据.方法 选取FTLD患者23例(bvFTD 10例,PPA 13例)、AD患者30例及认知正常受试者(CN)30名,使用3.0T超导型MR仪及8通道头线圈行图像采集.以高分辨率的三维梯度回波序列(3D-TFE)横断面T1WI作为脑灰质皮层体积的计算序列,采用统计参数图(SPM)8和其工具箱[基于体素的形态测量学方法(VBM)]对3D-TFE T1 WI图像进行空间标准化预处理,最后得到灰质分割图像,进行灰质体积的统计分析,多重比较矫正采用假发现率法,用Xjview工具显示统计分析结果,体素簇大小设为5.采用4 mm的半高全宽高斯核进行空间平滑.统计学分析采用配对t检验.结果 与CN组比较,在bvFTD、PPA和AD组中均出现大脑皮层及皮质下结构(如海马、杏仁核、尾状核等)体积弥漫减少.在bvFTD和PPA组中最明显的萎缩脑区位于额颞叶.与AD组比较,bvFTD组灰质明显萎缩的脑区包括:两侧颞叶上中下回、颞极上回及中回、右侧梭状回和两侧额叶上中下回.颞叶和额叶萎缩具有明显的右侧偏侧性,右侧和左侧颞叶萎缩体素的总体数目为14 301个和5105个(t=-5.03,P＜0.05),右侧和左侧额叶萎缩体素的数目为1344个和125个(t=3.45,P＜0.05),差异均有统计学意义.在PPA组中左侧颞枕叶萎缩明显大于右侧(t=-2.65,P＜0.05),左侧和右侧颞枕叶萎缩体素的数目为15 637个和10 723个.结论 bvFTD、PPA与AD3组具有不同的脑灰质萎缩模式.其中,bvFTD具有右侧额叶和颞叶萎缩的非对称分布特点,与性格改变的特征性表现相关;而PPA具有左侧颞枕叶非对称性萎缩的特点,可解释PPA患者出现语言障碍的特点.     

基于MRI的早期盲人海马体积分析研究

【摘要】目的：采用3.0 T磁共振对早期盲人与视力正常人的海马结构进行定量测量，探讨早期盲人与视力正常人之间海马结构的体积差异。方法：对早期盲人与视力正常人各22例行颅脑MRI扫描，获得3D-T1WI图像并对每个个体的两侧海马进行手动分割，测量海马体积并比较两组之间海马体积整体及前、中、后部体积差异。结果：早期盲人组及视力正常组的海马均有半球差异，表现为右侧海马总体积明显大于左侧，差异有统计学意义（P＜0.05）。视力正常组左、右侧海马总体积大于早期盲人组，差异有统计学意义（P＜0.05）；且早期盲人组右侧海马后部和左侧海马中部体积小于视力正常组，差异有统计学意义（P＜0.05）。结论：早期盲人组及视力正常组的右侧海马总体积均大于左侧，与视力正常组相比早期盲人组双侧海马总体积明显缩小，以右侧海马后部和左侧海马中部为著。     

中国汉族正常成人尾状核的高分辨率MRI测量

目的 测量中国汉族正常成人尾状核体积,为建立中国成人数字标准脑提供基础数据.方法 采用全国多中心临床研究形式,选取18～70岁健康志愿者1000名,按照年龄18～30、31～40、41～50、51～60、61～70岁进行分组,每组男、女各100名.所有受试者均行三维磁化强度预备梯度回波序列T1WI,应用三维体积分析软件手工勾绘ROI,测量尾状核的体积,探讨尾状核体积的性别、侧别差异及与年龄的相关关系.组间比较采用独立样本t检验,年龄与体积进行Pearson相关分析,左、右两侧对照使用配对t检验.结果 正常中国成人两侧尾状核体积之和为(10.973 ±1.647)cm3.男性左、右侧尾状核体积分别为(5.656±0.860)、(5.671±0.855)cm3,差异无统计学意义(t=1.230,P>0.05).女性左、右侧尾状核体积分别为(5.287±0.774)、(5.331±0.766)cm3,右侧大于左侧(t=3.999,P<0.01).相关性分析示男、女性的左、右侧尾状核体积均与年龄呈明显负相关(r值分别为-0.561、-0.568、-0.548、-0.552,P值均<0.05).结论 高分辨率MRI和三维体积分析软件可以准确测量尾状核的体积,为中国成人数字标准脑提供基础性数据.     

磁共振波谱在不同认知功能损害中的应用

目的：探讨轻度认知功能障碍(MCI)患者、阿尔茨海默病(AD)患者、正常认知(NC)者3组人群海马区代谢物比值的区别。方法收集 MCI 组(30例)、AD 组(28例)及 NC 组(30例)行双侧海马区氢质子磁共振波谱(1 H MRS)检查,比较 MCI 组、AD组和 NC 组左右两侧各组间 NAA/Cr、Ins/Cr、NAA/Ins、Cho/Cr 比值差别。结果MCI 组和 AD 组双侧 NAA/Cr 比值均明显低于NC 组,经统计学分析有显著性差异(P 值均<0.05)。MCI 组、AD 组右侧 Ins/Cr 比值、NAA/Ins 比值分别与 NC 组有显著性差异(P 值均<0.05)。MCI 组、AD 组和 NC 组左侧 Ins/Cr、NAA/Ins 比值3组间比较均有显著性差异(P 值均<0.05)。结论1 H MRS 作为无创性诊断技术,在早期 MCI、AD 诊断及鉴别诊断中具有较高的敏感性。     

基于体素的形态测量学在阿尔茨海默病和轻度认知障碍中的应用价值

目的：应用基于体素的形态测量学（VBM）方法比较阿尔茨海默病（AD）和轻度认知障碍（MCI）患者和健康老年人灰质体积的不同,探讨VBM方法在AD、MCI诊断中的应用价值。方法：本研究包括10例AD患者（AD组）、9例MCI患者（MCI组）、10例老年健康志愿者（健康对照组）,检查系列包括头常规轴面T2WI、T1WI、轴面FLAIR、矢状面T1WI,全脑3D-SPGR。应用VBM方法处理数据,把脑组织分割成灰质、白质和脑脊液,最后应用两样本t检验两两比较灰质体积改变。结果：AD组与正常对照组脑灰质体积比较：AD组大脑皮层灰质体积弥漫减少,激活区域几乎分布整个大脑半球,以两侧内侧颞叶（海马、梨状皮层、内嗅皮层）为著。右侧海马减少的体素总数为2358个,左侧海马减少的体素总数为2967个,前后扣带回体素明显减少;MCI组与正常对照组比较：MCI组灰质减少的区域依然较多,但与AD和对照组相比,激活区域明显减少。其中最明显的是内侧颞叶内嗅皮层、海马旁回区域,右侧体素减少总数为1368,左侧1135;MCI组和AD组的比较：MCI组较AD组灰质减少的区域更多,内侧颞叶和海马区域基本没有激活区域,较明显的激活区域位于双侧额顶颞叶、扣带回。双侧尾状核头部和左侧丘脑亦有较明显激活,而豆状核没有明显激活。结论：内侧颞叶和海马体积减小是评价AD和MCI最敏感的区域,VBM可以有效评价灰质体积的改变。     

中国汉族正常成人扣带回的高分辨率MRI测量

目的 建立中国汉族正常成人扣带回体积的正常值范围,探讨扣带回体积与年龄的相关关系,为中国成人数字标准脑提供基础性数据.方法 采用全国多中心临床研究形式,选取1000名中国健康成年志愿者,按年龄18～30、31～40、41～50、51～60、61～70岁分为A、B、C、D、E组,每组男、女各100名,行大脑3D磁化强度预备梯度回波序列T1WI,应用3D体积分析软件测量扣带回的体积.不同年龄组扣带回体积的比较采用方差分析,不同性别、侧别扣带回体积的比较采用配对样本t检验,扣带回体积与年龄进行相关与回归分析.结果 男、女扣带回总体积分别为(20 347±2504)、(19 432±2184)mm3,差异有统计学意义(方差不齐,采用两组独立样本t'检验,t'=6.156,P<0.05),男性扣带回总体积大于女性.男性左、右侧扣带回体积分别为(9630±1498)、(10 717±1629)mm3,女性分别为(9368±1441)、(10064±1407)mm3,男、女不同侧别扣带回体积比较差异均有统计学意义(t值分别为-12.960、-8.511,P值均<0.05),右侧扣带回体积均大于左侧.男性A、B、C、D、E组扣带回体积:左侧分别为(10 132±1291)、(10 113±1638)、(9599±1576)、(9594 ±1288)、(8710 ±1212)mm3,右侧分别为(11 212±1442)、(11 096±1602)、(11 040 ±1403)、(10 633±1638)、(9604 ±1522)mm3,不同年龄组间差异有统计学意义(F值分别为16.738、18.707,P值均<0.01).女性A、B、C、D、E组扣带回体积:左侧分别为(9689 ±1426)、(9652±1676)、(9347±1500)、(9098±1225)、(9053±1233)mm3,右侧分别为(10 558 ±1325)、(10 266 ±1463)、(10 100±1497)、(9779±1304)、(9617±1254)mm3,不同年龄组间差异有统计学意义(F值分别为16.859、7.528,P值均<0.01).男、女双侧扣带回体积与年龄均存在负相关(r值分别为-0.330、-0.324、-0.169、-0.243,P值均<0.05),但相关性不强.结论 基于高分辨率MR图像和3D体积分析软件可以准确测量扣带回的体积,为中国成人数字标准脑提供基础性数据,为可能引起扣带回体积改变的相关疾病诊断提供正常对照标准.     

青年人与老年人海马体积及形态的MR研究

目的 在区分海马标志点的基础上,测量青年人和老年人正常海马及其头、体、尾3个部位的体积、形态.方法 选择正常青年人(年龄20～29岁,青年组)和老年人(60岁以上,老年组)志愿者各30名进行头部MR扫描,所得图像经后处理软件分析,确定较恒定、易辨认的解剖标志点后对海马进行分割.测量青年组和老年组海马的体积、平均扫描层面积及扫描层数,两组间以及青年组和老年组不同性别、不同侧别海马体积的比较采用独立样本t检验,并作海马的三维重建.结果 60名受试者钩隐窝、脑室三角、钩顶等均能清晰显示.青年组和老年组不同性别间海马体积差异均无统计学意义.青年组左侧海马头部、体部、尾部及整体体积分别为(1250±174)、(653±115)、(372±116)、(2277±109)mm~3,右侧分别为(1255±147)、(657±129)、(386±105)、(2298±213)mm~3,左、右侧间差异均无统计学意义(t值分别为0.08、0.10、0.33、0.35,P值均＞0.05).老年组左侧海马头部、体部、尾部及整体体积分别为(660±109)、(472±92)、(181±73)、(1313±163)mm~3,右侧分别为(717±116)、(474±95)、(240±75)、(1432±171)mm~3,右侧海马尾部体积明显大于左侧,差异具有统计学意义(t=2.21,P＜0.05);其他部位左、右侧海马体积差异均无统计学意义(t值分别为1.39、0.06、1.95,P值均＞0.05).青年组和老年组左侧海马头部、体部、尾部及整体体积差异均有统计学意义(t值分别为15.78、6.71、7.70、20.83,P值均＜0.05),右侧各部位差异也均有统计学意义(t值分别为15.76、6.26、6.15、17.36,P值均＜0.05).老年组各部位体积明显小于青年组,其中以头部最为明显.青年组及老年组海马头部左侧层面积分别为(75±24)、(56±21)mm~2,右侧层面积分别为(73±22)、(58±19)mm2,两组间差异均有统计学意义(t值分别为3.33、2.81,P值均＜0.01).青年组及老年组左侧层数分别为(11.1±3.2)、(7.9±3.9)层,右侧层数分别为(11.5±3.7)、(8.2±3.1)层,两组间差异也均有统计学意义(t值分别为3.48、3.75,P值均＜0.05).老年组的海马头部层数和层面积均小于青年组,呈短而窄的外形.结论 根据海马标志点确认的原则,其所提出的标志点为海马形态体积的标准化测量提供了测量的基础,其所测的正常值有助于疾病的诊断或为某些疾病发病机制的研究提供基础.     

AD与MCI患者注意功能障碍的功能磁共振对比研究

目的探究阿尔茨海默病(Alzheimer’s disease,AD)与轻度认知障碍(mild cognitive impairment,MCI)患者背侧与腹侧注意网络功能连接异常。方法对17例AD患者、16例MCI患者与16例正常老年被试者进行功能磁共振扫描,采用独立成分分析方法提取三组被试者背侧(dorsal attention network,DAN)与腹侧注意网络(ventral attention network,VAN)功能连接图像,应用单因素方差分析进行组间对比。结果 DAN内包括左侧额眼区与顶下沟区域以及扣带回后部等区域具有显著组间差异;而VAN内在额下回/额中回眶部以及背侧额中/下回等部位具有显著组间差异。对感兴趣区进行两两比较发现AD组表现出全局性注意网络衰退,而MCI组表现出选择性注意网络衰退,其中背侧出现连接降低,而腹侧连接无显著异常。结论 AD与MCI患者静息态注意网络功能连接的差异可能是注意行为能力差异的神经机制,反映了痴呆进展过程中神经退行变与神经代偿程度。     

海马体积测量联合 MMSE 评分在认知障碍中的应用

目的：探讨测量海马体积(HV)联合简易智力状况检查量表(MMSE)评分评估不同程度认知功能障碍的价值。方法收集阿尔茨海默病(AD)患者、轻度认知障碍(MCI)患者、正常对照(NC)各30例,应用西门子 MRI 行 HV 测量,综合分析3组患者标准化后的 HV、MMSE 评分。结果与 MCI、NC 组比较,AD 组总 HV、左右侧均减小,差别有统计学意义(P 值均<0.05);MCI 与 NC 2组之间 HV 无显著差异;分析3组患者的 MMSE 评分,AD 组分值均小于 MCI、NC 组,差别有统计学意义(P 值均<0.05),MMSE 评分在MCI 与 NC 2组间无差别。结论HV 测量联合 MMSE 评分,有助于为 AD 患者诊断提供有价值的信息,而在 MCI 中的诊断灵敏度不高。     

131I-IMPY脑显像对Alzheimer病的诊断价值

目的探讨Ap斑块显像剂131I-2一（4’-二甲基氨基苯基）一6-碘咪唑并[1,2-α]吡啶（IMPY）脑SPECT显像对AD的诊断价值。方法对13例AD患者（男3例,女10例,年龄52～79岁）、11例轻度认知损害（MCI）期患者（男4例,女7例,年龄48～67岁）及14名健康志愿者（男6名,女8名,年龄42一一67岁）静脉注射”‘I-IMPY37～74MBq,2—3h后行脑SPECT显像,用ROI技术半定量分析方法计算脑听眦线横断面、矢状面各脑区／d,It~放射性摄取比值（Rcl／cb）,并进行两样本间t检验。结果MCI患者中,顶叶、颞叶及额叶与小脑Rcl／cb增加,右侧分别为1．15±0．18,1．18±0．12,1．14±0．14;左侧分别为1．16±0．11,1．19±0．18,1．15±0．09,其与健康志愿者（右侧：1．02±0．12,1．05±0．14,1．0l±0．12;左侧：1．03±0．13,1．05±0．13,1．01±0．14）相比差异有统计学意义（t=2．1642～2．8757,P均〈0．05）,而基底部和枕叶与小脑的Rcl／cb右侧为0．92±0．18,1．12±0．15;左侧为0．94±0．15,1．13±0．17,与健康志愿者（右侧：0．82±0．15,1．06±0．18;左侧：0．85±0．16,1．08±0．15）相比差异无统计学意义（t=0．7805～1．4344,P均〉0．05）;AD患者中,顶叶、颞叶、额叶、基底部和枕叶与小脑的Rel／cb均有不同程度的增加,右侧为1．16±0．19,1．24±0．17,1．16±0．13,1．14±0．11,1．23±0．10;左侧为1．17±0。2l,1．25-t-O．15,1．18±0．08,1．17±0．16,1．25±0．11,其与健康志愿者相比差异均有统计学意义（t=2．1001～6．2789,P均〈0．05）,其中顶叶、颞叶、额叶与小脑的Rcl／cb与MCI患者相比差异无统计学意义（t：0．1316～0．9806,P均〉0。05）,基底部和枕叶与小脑的Rcl／cb增加,其与MCI患者相比差异有统计学意义（t=2．0850～3．6772,P均〈0．05）。结论131I-IMPY脑SPECT显像是诊断AD的有效方法,有助于AD的早期诊断。     

Is radiological evaluation as good as computer-based volumetry to assess hippocampal atrophy in Alzheimer’s disease?

Introduction

Hippocampus volumetry is a useful surrogate marker for the diagnosis of Alzheimer??s disease (AD). Our purpose was to compare visual assessment of medial temporal lobe atrophy made by radiologists with automatic hippocampal volume and to compare their performances for the classification of AD, mild cognitive impairment (MCI) and cognitively normal (CN).

Methods

We studied 30 CN, 30 MCI and 30 AD subjects. Six radiologists with two levels of expertise performed two readings of medial temporal lobe atrophy. Medial temporal lobe atrophy was evaluated on coronal three-dimensional T1-weighted images using Scheltens scale and compared with hippocampal volume obtained using a fully automatic segmentation method (Spearman??s rank coefficient).

Results

Visual assessment of medial temporal lobe atrophy was correlated with hippocampal volume (p?<?0.01). Classification performances between MCI converter and CN was better using volumetry than visual assessment of non-expert readers whereas classification of AD and CN did not differ between visual assessment and volumetry except for the first reading of one non-expert (p?=?0.03).

Conclusions

Visual assessment of medial temporal lobe atrophy by radiologists was well correlated with hippocampal volume. Radiological assessment is as good as computer-based volumetry for the classification of AD, MCI non-converter and CN and less good for the classification of MCI converter versus CN. Use of Scheltens scale for assessing hippocampal atrophy in AD seems thus justified in clinical routine.     

Role of neuroimaging in Alzheimer's disease, with emphasis on brain perfusion SPECT.

Structural MRI and functional imaging by SPECT as well as 18F-FDG PET are widely used in the diagnosis of Alzheimer's disease (AD). Metabolic and perfusion reductions in the parietotemporal association cortex are recognized as a diagnostic pattern for AD. Outstanding progress in the diagnostic accuracy of these modalities has been achieved with statistical analysis on a voxel-by-voxel basis after anatomic standardization of individual scans to a standardized brain volume template instead of visual inspection or a volume-of-interest technique. In a very early stage of AD, this statistical approach revealed losses of gray matter in the entorhinal and hippocampal areas and hypometabolism or hypoperfusion in the posterior cingulate cortex and precuneus. This statistical approach also offers a prediction of the conversion from mild cognitive impairment (MCI) to AD. The presence of hypometabolism or hypoperfusion in parietal association areas and entorhinal atrophy at the MCI stage have been reported to predict a rapid conversion to AD. A recent advance in voxel-based statistical analysis has markedly enhanced the value of brain perfusion SPECT in diagnosing early AD at the stage of MCI.     

阿尔茨海默病与轻度认知障碍患者初级嗅觉皮层的形态与功能改变

目的 确定阿尔茨海默病(AD)与轻度认知障碍(MCI)患者中初级嗅觉皮层的萎缩程度,并且探讨解剖学萎缩与嗅觉功能减低的内在联系.方法 选取12例AD、8例MCI患者和20名正常志愿者(NC),进行标准的嗅觉功能和神经学评分,而后进行高分辨率MRI和嗅觉fMRI.于T_1WI上确定初级嗅觉皮层的边界,并测量常规初级嗅觉皮层的容积,将此容积保存为ROI.然后采用事件相关的实验设计进行嗅觉fMRI,测量初级嗅觉皮层ROI内的激活体素.3组间的初级嗅觉皮层体积和激活范围比较采用Kruskal-Wallis秩和检验,如存在统计学差异则进行Bonferroni法两两比较.解剖学体积与激活范围情况的相关性在控制年龄因素下进行偏相关性分析.结果 NC、MCI和AD组初级嗅觉皮层的体积范围分别为3024～4734、1409～4553和1561～3759 mm~3,中位数分别为3749、2752和2156 mm~3;激活体素范围分别为0～2360、0～2160和0～100 mm~3,中位数分别为430、40和0 mm~3,NC、MCI和AD组初级嗅觉皮层体积和激活体素依次降低,差异有统计学意义(H值分别为14.942、16.587,P值均<0.05).初级嗅觉皮层内的激活与皮层体积的萎缩存在弱相关性(r=0.364,P=0.023).结论 AD初级嗅觉皮层存在明显萎缩与功能障碍,可以为AD的嗅觉功能障碍研究提供神经病理学和神经功能学依据.     

Volume changes in Alzheimer’s disease and mild cognitive impairment: cognitive associations

Objective

To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer’s disease (AD), mild cognitive impairment (MCI) and control subjects.

Material and methods

In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer’s disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period.

Results

Brain atrophy rates and ventricular enlargement differed between subject groups (p?<?0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p?<?0.0005) and ventricular expansion rates (p?=?0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects.

Conclusion

Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers.     

Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience

PURPOSE: To prospectively determine if pulsed arterial spin-labeling perfusion magnetic resonance (MR) imaging depicts regional cerebral hypoperfusion in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI), compared with perfusion in cognitively normal (CN) subjects, that is consistent with results of fluorodeoxyglucose (FDG) positron emission tomography (PET) and hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) studies of similar populations. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty subjects with AD (13 men, seven women; mean age, 72.9 years), 18 with MCI (nine men, nine women; mean age, 73.3 years), and 23 CN subjects (10 men, 13 women; mean age, 72.9 years) underwent arterial spin-labeling and volumetric T1-weighted structural MR imaging. Perfusion images were coregistered to structural images, corrected for partial volume effects (PVEs) with information from the structural image to determine tissue content of perfusion voxels, and normalized to a study-specific template. Analyses of perfusion differences between groups, with and without corrections for PVEs, were performed on a voxel-by-voxel basis with a one-tailed fixed-effects analysis of covariance model adjusted for age. In addition, tests were performed with and without accounting for global perfusion. RESULTS: The AD group showed significant regional hypoperfusion, compared with the CN group, in the right inferior parietal cortex extending into the bilateral posterior cingulate gyri (P <.001), bilateral superior and middle frontal gyri (P <.001), and left inferior parietal lobe (P=.007). When PVEs from underlying cortical gray matter atrophy were accounted for, the AD group still showed hypoperfusion in the right inferior parietal lobe extending into the bilateral posterior cingulate gyri (P <.001) and left (P=.003) and right (P=.012) middle frontal gyri. With a more liberal voxel-level threshold of P <.01, the MCI group showed significant regional hypoperfusion relative to the CN group in the inferior right parietal lobe (P=.046), similar to the region of greatest significance in the AD group. CONCLUSION: Arterial spin-labeling MR imaging showed regional hypoperfusion with AD, in brain regions similar to those seen in FDG PET and HMPAO SPECT studies of similar populations; this hypoperfusion persists after accounting for underlying cortical gray matter atrophy.     

Hippocampal atrophy confounds template-based functional MR imaging measures of hippocampal activation in patients with mild cognitive impairment

BACKGROUND AND PURPOSE: Functional MR imaging has been used to study patterns of hippocampal activation that distinguish pathologic from normal memory loss in the elderly population. Our objective was to assess whether hippocampal atrophy confounds measurements of hippocampal activation in subjects with mild cognitive impairment (MCI). METHODS: Twenty subjects with MCI and 20 elderly control subjects with objectively normal memory were studied at 4T during a face-name paradigm designed to activate the hippocampus. Hippocampal activation was measured using 2 separate approaches: applying a preset region of interest (ROI) in standardized template space and applying a manually drawn ROI in native subject space. Pearson correlation coefficients were calculated to compare group-dependent relationships between hippocampal volume and activation. Analysis of covariance (ANCOVA) was performed to assess group differences in hippocampal activation during encoding and retrieval. Age and hippocampal volume were included as covariates, as was a term for the interaction between hippocampal volume and group. RESULTS: When hippocampal activation was measured by the template-based method, the correlation coefficient in the right hippocampus of subjects with MCI but not control subjects during retrieval differed significantly from zero. There was a significant (P < .05) group-by-volume interaction in the ANCOVA model. No significant correlations or interactions were demonstrated when activation was measured in native subject space with manually drawn ROIs. CONCLUSION: Our findings suggest a potential confounding relationship between hippocampal volume and activation for subjects with MCI in template-based analyses. Template-based measures of hippocampal activation that do not adequately account for hippocampal atrophy should be used with caution in patients with MCI.