From the Department of Neurology (E.G., R.B.L., A.E.V., A.E.), Albert Einstein College of Medicine, Bronx, NY; Harvard Aging Brain Study (R.A.S., K.V.P., K.A.J., D.M.R.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment (R.A.S., K.V.P., K.A.J., D.M.R.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; and Alzheimer's Therapeutic Research Institute (P.S.A.), University of Southern California, San Diego.
Neurology. 2022 Mar 29;98(13):e1327-e1336. doi: 10.1212/WNL.0000000000200046. Epub 2022 Feb 23.
The goal of this work was to investigate the neuroimaging correlates of the Stages of Objective Memory Impairment (SOMI) system operationalized with the Free and Cued Selective Reminding Test (FCSRT), a widely used episodic memory measure.
The FCSRT begins with a study phase in which items (e.g., grapes) are identified in response to unique semantic cues (e.g., fruit) that are used in the test phase to prompt recall of items not retrieved by free recall. There are 3 test trials of the 16 items (maximum 48). Data from 4,484 cognitively unimpaired participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study were used. All participants had amyloid PET imaging, and a subset of 1,262 β-amyloid (Aβ)-positive had structural MRIs. We compared the Aβ mean cortical standardized uptake value ratio (SUVR) and volumetric measures of hippocampus, parahippocampal gyrus, entorhinal cortex, and inferior temporal cortex between the 5 SOMI stages.
Participants had a mean age of 71.3 (SD 4.6) years; 40.6% were male; and 34.6% were ε4 positive. Half had no memory impairment; the other half had retrieval deficits, storage limitations, or both. Analysis of covariance in the entire sample while controlling for age, sex, education, and ε4 showed that individuals in higher SOMI stages had higher global amyloid SUVR ( < 0.001). Both SOMI-4 and -3 subgroups had higher amyloid SUVR than SOMI-0 and SOMI-1 subgroups. Individuals in higher SOMI stages had smaller hippocampal volume ( = 0.003), entorhinal cortex ( < 0.05), and inferior temporal lobes ( < 0.05), but there was no difference between parahippocampal gyrus volume of different SOMI stages. Pairwise comparison of SOMI subgroups showed that the SOMI-4, -3, and -2 subgroups had smaller hippocampal volume than the SOMI-0 and -1 subgroup. The SOMI-4 subgroup had significantly smaller entorhinal cortex and smaller inferior temporal lobe compared to all other groups.
Presence of Alzheimer disease pathology is closely related to memory impairment according to SOMI stages in the cognitively unimpaired sample of A4. Results from structural MRIs suggest that memory storage impairment (SOMI-3 and -4) is present when there is widespread medial temporal lobe atrophy.
ClinicalTrials.gov identifier: NCT02008357.
This study provides Class I evidence that, in normal older individuals, higher stages of memory impairment assessed with FCSRT were associated with higher amyloid imaging burden and lower volume of hippocampus, entorhinal cortex, and inferior temporal lobes.
本研究旨在探讨使用广泛应用于情景记忆测试的自由和线索选择性回忆测试（FCSRT）操作性定义的客观记忆损害阶段（SOMI）系统的神经影像学相关性。
FCSRT 从学习阶段开始，在此阶段，参与者需要根据独特的语义线索（例如水果）识别物品（例如葡萄），这些线索在测试阶段用于提示回忆未通过自由回忆检索到的物品。共有 3 个包含 16 个项目的测试试验（最多 48 个）。本研究使用了来自 Anti-Amyloid Treatment in Asymptomatic Alzheimer's（A4）研究的 4484 名认知正常的参与者的数据。所有参与者均接受了淀粉样蛋白 PET 成像，亚组的 1262 名β-淀粉样蛋白（Aβ）阳性参与者接受了结构 MRI。我们比较了 5 个 SOMI 阶段的 Aβ 平均皮质标准化摄取值比（SUVR）和海马体、海马旁回、内嗅皮层和颞下回的体积测量值。
参与者的平均年龄为 71.3（SD 4.6）岁；40.6%为男性；34.6%为 ε4 阳性。有一半参与者没有记忆障碍，另一半参与者存在检索缺陷、存储限制或两者兼有。在整个样本中进行协方差分析，同时控制年龄、性别、教育程度和 ε4，结果表明处于较高 SOMI 阶段的个体具有更高的全局淀粉样蛋白 SUVR（<0.001）。SOMI-4 和 -3 亚组的淀粉样蛋白 SUVR 均高于 SOMI-0 和 SOMI-1 亚组。处于较高 SOMI 阶段的个体的海马体体积较小（=0.003），内嗅皮层（<0.05）和颞下回体积较小（<0.05），但不同 SOMI 阶段的海马旁回体积没有差异。SOMI 亚组的两两比较显示，SOMI-4、-3 和 -2 亚组的海马体体积均小于 SOMI-0 和 -1 亚组。与所有其他组相比，SOMI-4 亚组的内嗅皮层和颞下回明显较小。
在认知正常的 A4 样本中，根据 SOMI 阶段，阿尔茨海默病病理学的存在与记忆障碍密切相关。结构 MRI 的结果表明，当内侧颞叶广泛萎缩时，就会出现记忆存储障碍（SOMI-3 和 -4）。
ClinicalTrials.gov 标识符：NCT02008357。
本研究提供了 I 级证据，表明在正常老年个体中，使用 FCSRT 评估的更高阶段的记忆损伤与更高的淀粉样蛋白成像负担以及海马体、内嗅皮层和颞下回体积降低有关。
