CIRD Centre d'Imagerie Rive Droite, Geneva, Switzerland,
Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden,
Neurodegener Dis. 2019;19(3-4):139-147. doi: 10.1159/000504302. Epub 2019 Dec 17.
Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions.
We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL.
There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele.
The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.
海马体积损失（HVL）、正电子发射断层扫描（PET）记录的脑淀粉样蛋白积累和 APOE-ε4 状态是从轻度认知障碍到阿尔茨海默病（AD）转变的预测生物标志物。在无症状病例中，这些生物标志物的作用仍不明确。与 HVL 发生在神经退行性变晚期的观点相反，最近的研究表明，它可能在老年患者出现异常淀粉样 PET 之前发生，其严重程度可能与 APOE 变体仅有轻微相关。使用纵向设计，我们检查了我们样本中 HVL 的决定因素，即脑淀粉样蛋白负担和 APOE-ε4 的存在，并对认知功能进行了纵向评估。
我们对 81 名老年社区居民进行了 4.5 年的纵向研究（均为右利手，48 名（59.3%）为女性；平均年龄 73.7±3.7 岁），包括基线和随访时的 MRI、随访期间的 PET 淀粉样蛋白、18 个月和 54 个月时的神经心理学评估和 APOE 基因分型。所有病例均采用连续认知评分（CCS）进行评估，该评分考虑了神经心理学表现的整体变化。使用线性回归模型确定 HVL 的预测因素。
CCS 与双侧 HVL 呈负相关。在调整人口统计学变量的多变量模型中，APOE-ε4 的存在与双侧 HVL 增加有关。在左半球，淀粉样蛋白阳性对 HVL 的影响呈显著趋势。未发现淀粉样蛋白阳性与 APOE-ε4 等位基因之间存在显著交互作用。
在出现临床明显症状之前，神经心理学表现的逐渐下降与 HVL 有关。在这个健康个体队列中，APOE-ε4 等位基因的存在被证明是无症状病例中与淀粉样蛋白阳性无关的独立预测因子，预测最差的海马完整性。
