Objective: To evaluate in 419 stroke-free cognitively normal subjects (CN) aged 45-82 years covering during a long prospective study (11.54 ± 1.47 years) the preclinical to dementia spectrum: 1) the distribution of small vessel disease (V) and brain atrophy (A) aggregated as following: V−/A−, V−/A+, V+/A−, V+/A+; 2) the relationship of these imaging classes with individual apolipoprotein E (APOE) genotypes; 3) the risk of progression to Alzheimer Disease (AD) of the individual APOE genotypes.

Methods: Participants underwent one baseline (t0), and 4 clinical and neuropsychological assessments (t1,t2,t3, and t4). Brain MRI was performed in all subjects at t0, t2, t3 and t4.. White matter hyperintensities were assessed through two visual rating scales. Lacunes were also rated. Subcortical and global brain atrophy were determined through the bicaudate ratio and the lateral ventricle to brain ratio, respectively. APOE genotypes were determined at t0 in all subjects. Cox proportional hazard model was used to evaluate the risk of progression to AD.

Results: The imaging class of mixed type was very common in AD, and in non amnestic mild cognitive impaired APOE ε4 non carriers. In these subjects, frontal and parieto-occipital regions were most affected by small vessel disease.

Conclusion: Our findings suggest that the APOE ε3 allele is probably linked to the brain vascular pathology.

目的：在一项长期前瞻性研究（11.54 ± 1.47 岁）中评估 419 名 45-82 岁无中风认知正常受试者 (CN) 的临床前至痴呆谱：1) 小血管疾病 (V) 和脑萎缩 (A) 汇总如下：V-/A-、V-/A+、V+/A-、V+/A+；2) 这些成像类别与单个载脂蛋白 E (APOE) 基因型的关系；3) 个体 APOE 基因型进展为阿尔茨海默病 (AD) 的风险。

方法：参与者接受了一次基线（t0）和 4 次临床和神经心理学评估（t1、t2、t3 和 t4）。在 t0、t2、t3 和 t4 对所有受试者进行脑 MRI。通过两个视觉评定量表评估白质高信号。也对缺损进行了评级。皮质下和全脑萎缩分别通过双尾比和侧脑室与脑的比来确定。所有受试者在 t0 时确定 APOE 基因型。Cox 比例风险模型用于评估进展为 AD 的风险。

结果：影像学类型混合型在 AD 和非遗忘型轻度认知障碍 APOE ε4 非携带者中非常常见。在这些受试者中，额叶和顶枕叶区域受小血管疾病的影响最大。

结论：我们的研究结果表明 APOE ε3 等位基因可能与脑血管病理学有关。