INTRODUCTIONWe assessed a genetic risk score for Alzheimer's disease (AD‐GRS) and apolipoprotein E (APOE4) in an exploratory neuroimaging substudy of the FINGER trial.METHODS1260 at‐risk older individuals without dementia were randomized to multidomain lifestyle intervention or health advice. N = 126 participants underwent magnetic resonance imaging (MRI), and N = 47 positron emission tomography (PET) scans (Pittsburgh Compund B [PiB], Fluorodeoxyglucose) at baseline; N = 107 and N = 38 had repeated 2‐year scans.RESULTSThe APOE4 allele, but not AD‐GRS, was associated with baseline lower hippocampus volume (β = −0.27, p = 0.001), greater amyloid deposition (β = 0.48, p = 0.001), 2‐year decline in hippocampus (β = −0.27, p = 0.01), total gray matter volume (β = −0.25, p = 0.01), and cortical thickness (β = −0.28, p = 0.003). In analyses stratified by AD‐GRS (below vs above median), the PiB composite score increased less in intervention versus control in the higher AD‐GRS group (β = −0.60, p = 0.03).DISCUSSIONAD‐GRS and APOE4 may have different impacts on potential intervention effects on amyloid, that is, less accumulation in the higher‐risk group (AD‐GRS) versus lower‐risk group (APOE).Highlights First study of neuroimaging and AD genetics in a multidomain lifestyle intervention. Possible intervention effect on brain amyloid deposition may rely on genetic risk. AD‐GRS and APOE4 allele may have different impacts on amyloid during intervention.

中文翻译：

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FINGER 生活方式试验中的阿尔茨海默病遗传风险评分和神经影像学

简介我们评估了阿尔茨海默病 (AD-GRS) 和载脂蛋白 E 的遗传风险评分（载脂蛋白4）在 FINGER 试验的一项探索性神经影像子研究中。方法 1260 名无痴呆症的高危老年人被随机分配接受多领域生活方式干预或健康建议。氮= 126 名参与者接受了磁共振成像 (MRI)，并且氮= 基线时 47 次正电子发射断层扫描 (PET) 扫描（匹兹堡化合物 B [PiB]，氟脱氧葡萄糖）；氮= 107 和氮= 38 人进行了 2 年重复扫描。结果载脂蛋白4等位基因（而非 AD-GRS）与基线较低海马体积相关（β = -0.27，p= 0.001），更大的淀粉样蛋白沉积（β = 0.48，p= 0.001），海马体下降 2 年（β = -0.27，p= 0.01），总灰质体积（β = -0.25，p= 0.01）和皮质厚度（β = -0.28，p= 0.003）。在按 AD-GRS 分层的分析中（低于中位数与高于中位数），在较高 AD-GRS 组中，与对照组相比，干预组的 PiB 综合评分增加较少（β = -0.60，p= 0.03).讨论AD-GRS 和载脂蛋白4可能对淀粉样蛋白的潜在干预效果有不同的影响，即高风险组（AD-GRS）与低风险组相比，淀粉样蛋白的积累较少（APOE）。强调 多领域生活方式干预中神经影像学和 AD 遗传学的首次研究。 对大脑淀粉样蛋白沉积的可能干预效果可能取决于遗传风险。 AD-GRS 和 APOE4 等位基因在干预过程中可能对淀粉样蛋白产生不同的影响。