Risacher Shannon L, Anderson Wesley H, Charil Arnaud, Castelluccio Peter F, Shcherbinin Sergey, Saykin Andrew J, Schwarz Adam J
From the Department of Radiology and Imaging Sciences (S.L.R., A.J. Saykin, A.J. Schwarz), Indiana Alzheimer Disease Center (S.L.R., A.J. Saykin), and Department of Biostatistics (P.F.C.), Indiana University School of Medicine; Eli Lilly and Company (W.H.A., A.C., S.S., A.J. Schwarz), Indianapolis; and Department of Psychological and Brain Sciences (A.J. Schwarz), Indiana University, Bloomington.
Neurology. 2017 Nov 21;89(21):2176-2186. doi: 10.1212/WNL.0000000000004670. Epub 2017 Oct 25.
To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline.
Amyloid-positive participants with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSp], limbic predominant [LP], typical AD [tAD]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models.
When participants were divided categorically, the HpSp group showed significantly more AD-like hypometabolism on F-fluorodeoxyglucose-PET ( < 0.05) and poorer baseline executive function ( < 0.001). Other baseline clinical measures did not differ across the 3 groups. Participants with HpSp also showed faster subsequent clinical decline than participants with LP on the Alzheimer's Disease Assessment Scale, 13-Item Subscale (ADAS-Cog), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all < 0.05) and tAD on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both < 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog score ( < 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy.
AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation.
检验以下假设，即通过容积磁共振成像（vMRI）扫描进行的体内测量的皮质和海马体积，可用于识别阿尔茨海默病（AD）的变异亚型，并前瞻性预测临床衰退率。
纳入来自阿尔茨海默病神经影像倡议（ADNI）1和ADNI2的淀粉样蛋白阳性AD参与者，他们有基线MRI扫描（n = 229）和2年临床随访（n = 100）。AD亚型（海马保留型[HpSp]、边缘叶为主型[LP]、典型AD[tAD]）根据一种类似于最近针对tau神经病理学提出的算法来定义。通过连续回归和分类模型研究基线海马体积与皮质体积比（HV:CTV）与临床变量之间的关系。
当对参与者进行分类时，HpSp组在氟代脱氧葡萄糖PET上显示出明显更多的AD样低代谢（< 0.05），且基线执行功能较差（< 0.001）。其他基线临床指标在3组之间没有差异。在阿尔茨海默病评估量表13项子量表（ADAS - Cog）、简易精神状态检查表（MMSE）和功能评估问卷上，HpSp组参与者随后的临床衰退也比LP组参与者更快（均< 0.05），在MMSE和临床痴呆评定量表框总和（CDR - SB）上比tAD组更快（均< 0.05）。最后，较高的HV:CTV与较差的基线执行功能以及CDR - SB、MMSE和ADAS - Cog评分更快的下降斜率相关（< 0.05）。这些关联主要由皮质而非海马萎缩的程度驱动。
通过vMRI可在体内识别出具有与tau神经病理学中观察到的表型一致的AD亚型。较高的HV:CTV比值可预测基线时除执行功能障碍表现更明显外临床无法区分的AD参与者更快的临床衰退。
