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Abstract：
The hippocampus is the most prominent single region of interest (ROI) for the diagnosis and prediction of Alzheimer\'s disease (AD). However, its suitability in the earliest stages of cognitive decline, i.e., subjective cognitive decline (SCD), remains uncertain which warrants the pursuit of alternative or complementary regions. The amygdala might be a promising candidate, given its implication in memory as well as other psychiatric disorders, e.g. depression and anxiety, which are prevalent in SCD. In this 7 tesla (T) magnetic resonance imaging (MRI) study, we aimed to compare the contribution of volumetric measurements of the hippocampus, the amygdala, and their respective subfields, for early diagnosis and prediction in an AD-related study population.
Participants from a longitudinal study were grouped into SCD (n = 29), mild cognitive impairment (MCI, n = 23), AD (n = 22) and healthy control (HC, n = 31). All participants underwent 7T MRI at baseline and extensive neuropsychological testing at up to three visits (baseline n = 105, 1-year n = 78, 3-year n = 39). Analysis of covariance (ANCOVA) was used to assess group differences of baseline volumes of the amygdala and the hippocampus and their subfields. Linear mixed models were used to estimate the effects of baseline volumes on yearly changes of a z-scaled memory score. All models were adjusted to age, sex and education.
Compared to the HC group, individuals with SCD showed smaller amygdala ROI volumes (range across subfields -11% to -1%), but not hippocampus ROI volumes (-2% to 1%) except for the hippocampus-amygdala-transition-area (-7%). However, cross-sectional associations between baseline memory and volumes were smaller for amygdala ROIs (std. ß [95% CI] ranging between 0.16 [0.08; 0.25] and 0.46 [0.31; 0.60]) than hippocampus ROIs (between 0.32 [0.19; 0.44] and 0.53 [0.40; 0.67]). Further, the association of baseline volumes with yearly memory change in the HC and SCD groups was similarly weak for amygdala ROIs and hippocampus ROIs. In the MCI group, volumes of amygdala ROIs were associated with a relevant yearly memory decline [95% CI] ranging between -0.12 [-0.24; 0.00] and -0.26 [-0.42; -0.09] for individuals with 20% smaller volumes than the HC group. However, effects were stronger for hippocampus ROIs with a corresponding yearly memory decline ranging between -0.21 [-0.35; -0.07] and -0.31 [-0.50; -0.13].
Volumes of amygdala ROIs, as determined by 7T MRI, might contribute to objectively and non-invasively identify patients with SCD, and thus aid early diagnosis and treatment of individuals at risk to develop dementia due to AD, however associations with other psychiatric disorders should be evaluated in further studies. The amygdala\'s value in the prediction of longitudinal memory changes in the SCD group remains questionable. Primarily in patients with MCI, memory decline over 3 years appears to be more strongly associated with volumes of hippocampus ROIs than amygdala ROIs.
Participants from a longitudinal study were grouped into SCD (n = 29), mild cognitive impairment (MCI, n = 23), AD (n = 22) and healthy control (HC, n = 31). All participants underwent 7T MRI at baseline and extensive neuropsychological testing at up to three visits (baseline n = 105, 1-year n = 78, 3-year n = 39). Analysis of covariance (ANCOVA) was used to assess group differences of baseline volumes of the amygdala and the hippocampus and their subfields. Linear mixed models were used to estimate the effects of baseline volumes on yearly changes of a z-scaled memory score. All models were adjusted to age, sex and education.
Compared to the HC group, individuals with SCD showed smaller amygdala ROI volumes (range across subfields -11% to -1%), but not hippocampus ROI volumes (-2% to 1%) except for the hippocampus-amygdala-transition-area (-7%). However, cross-sectional associations between baseline memory and volumes were smaller for amygdala ROIs (std. ß [95% CI] ranging between 0.16 [0.08; 0.25] and 0.46 [0.31; 0.60]) than hippocampus ROIs (between 0.32 [0.19; 0.44] and 0.53 [0.40; 0.67]). Further, the association of baseline volumes with yearly memory change in the HC and SCD groups was similarly weak for amygdala ROIs and hippocampus ROIs. In the MCI group, volumes of amygdala ROIs were associated with a relevant yearly memory decline [95% CI] ranging between -0.12 [-0.24; 0.00] and -0.26 [-0.42; -0.09] for individuals with 20% smaller volumes than the HC group. However, effects were stronger for hippocampus ROIs with a corresponding yearly memory decline ranging between -0.21 [-0.35; -0.07] and -0.31 [-0.50; -0.13].
Volumes of amygdala ROIs, as determined by 7T MRI, might contribute to objectively and non-invasively identify patients with SCD, and thus aid early diagnosis and treatment of individuals at risk to develop dementia due to AD, however associations with other psychiatric disorders should be evaluated in further studies. The amygdala\'s value in the prediction of longitudinal memory changes in the SCD group remains questionable. Primarily in patients with MCI, memory decline over 3 years appears to be more strongly associated with volumes of hippocampus ROIs than amygdala ROIs.
摘要：
背景：海马是诊断和预测阿尔茨海默病（AD）的最突出的单个感兴趣区域（ROI）。然而,它适用于认知衰退的早期阶段，即，主观认知能力下降（SCD），仍然不确定，哪些值得追求替代或互补区域。杏仁核可能是一个很有前途的候选者,考虑到它在记忆以及其他精神疾病中的含义，例如抑郁和焦虑，这在SCD中很普遍。在这项7特斯拉（T）磁共振成像（MRI）研究中，我们的目的是比较海马体体积测量的贡献，杏仁核,以及它们各自的子字段，用于AD相关研究人群的早期诊断和预测。
方法：将来自纵向研究的参与者分为SCD（n=29），轻度认知障碍（MCI，n=23），AD（n=22）和健康对照（HC，n=31）。所有参与者在基线时进行了7TMRI检查，并在多达3次访问时进行了广泛的神经心理学测试（基线n=105，1年n=78，3年n=39）。协方差分析（ANCOVA）用于评估杏仁核和海马及其子场的基线体积的组差异。线性混合模型用于估计基线体积对z标度记忆评分的年度变化的影响。所有模型都根据年龄进行了调整，性和教育。
结果：与HC组相比，患有SCD的个体显示出更小的杏仁核ROI体积(跨越子场的范围-11%至-1%)，但海马ROI体积（-2％至1％），海马-杏仁核过渡区（-7％）除外。然而,杏仁核ROI的基线记忆和体积之间的横断面关联较小（std.β[95%CI]范围在0.16[0.08;0.25]和0.46[0.31;0.60]之间)比海马体ROI(在0.32[0.19;0.44]和0.53[0.40;0.67]之间)。Further,在杏仁核ROI和海马ROI中,HC和SCD组的基线体积与年记忆变化的相关性同样较弱.在MCI组中,杏仁核ROI的体积与相关的年度记忆下降[95%CI]相关,对于体积比HC组小20%的个体,其范围在-0.12[-0.24;0.00]和-0.26[-0.42;-0.09]之间.然而,海马区ROI的影响更强，相应的年记忆下降范围在-0.21[-0.35;-0.07]和-0.31[-0.50;-0.13]之间。
结论：杏仁核ROI的体积，通过7TMRI确定，可能有助于客观和无创地识别SCD患者，因此，有助于早期诊断和治疗有患AD痴呆风险的个体，然而，与其他精神疾病的相关性应在进一步的研究中进行评估。杏仁核在预测SCD组纵向记忆变化中的价值仍然值得怀疑。主要在MCI患者中，超过3年的记忆力下降似乎与海马ROI的体积比杏仁核ROI更密切相关。
方法：将来自纵向研究的参与者分为SCD（n=29），轻度认知障碍（MCI，n=23），AD（n=22）和健康对照（HC，n=31）。所有参与者在基线时进行了7TMRI检查，并在多达3次访问时进行了广泛的神经心理学测试（基线n=105，1年n=78，3年n=39）。协方差分析（ANCOVA）用于评估杏仁核和海马及其子场的基线体积的组差异。线性混合模型用于估计基线体积对z标度记忆评分的年度变化的影响。所有模型都根据年龄进行了调整，性和教育。
结果：与HC组相比，患有SCD的个体显示出更小的杏仁核ROI体积(跨越子场的范围-11%至-1%)，但海马ROI体积（-2％至1％），海马-杏仁核过渡区（-7％）除外。然而,杏仁核ROI的基线记忆和体积之间的横断面关联较小（std.β[95%CI]范围在0.16[0.08;0.25]和0.46[0.31;0.60]之间)比海马体ROI(在0.32[0.19;0.44]和0.53[0.40;0.67]之间)。Further,在杏仁核ROI和海马ROI中,HC和SCD组的基线体积与年记忆变化的相关性同样较弱.在MCI组中,杏仁核ROI的体积与相关的年度记忆下降[95%CI]相关,对于体积比HC组小20%的个体,其范围在-0.12[-0.24;0.00]和-0.26[-0.42;-0.09]之间.然而,海马区ROI的影响更强，相应的年记忆下降范围在-0.21[-0.35;-0.07]和-0.31[-0.50;-0.13]之间。
结论：杏仁核ROI的体积，通过7TMRI确定，可能有助于客观和无创地识别SCD患者，因此，有助于早期诊断和治疗有患AD痴呆风险的个体，然而，与其他精神疾病的相关性应在进一步的研究中进行评估。杏仁核在预测SCD组纵向记忆变化中的价值仍然值得怀疑。主要在MCI患者中，超过3年的记忆力下降似乎与海马ROI的体积比杏仁核ROI更密切相关。
