PDF(Pubmed)
Abstract：
BACKGROUND: We assessed a genetic risk score for Alzheimer\'s disease (AD-GRS) and apolipoprotein E (APOE4) in an exploratory neuroimaging substudy of the FINGER trial.
METHODS: 1260 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.
RESULTS: The 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).
CONCLUSIONS: AD-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).
CONCLUSIONS: 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.
METHODS: 1260 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.
RESULTS: The 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).
CONCLUSIONS: AD-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).
CONCLUSIONS: 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.
摘要：
背景：我们在FINGER试验的一项探索性神经影像学亚研究中评估了阿尔茨海默病（AD-GRS）和载脂蛋白E（APOE4）的遗传风险评分。
方法：1260名未患痴呆的老年高危人群随机接受多领域生活方式干预或健康建议。N=126名参与者接受了磁共振成像（MRI），和N=47正电子发射断层扫描(PET)扫描(匹兹堡CompundB[PiB]，氟脱氧葡萄糖）在基线；N=107和N=38重复2年扫描。
结果：APOE4等位基因，但不是AD-GRS,与基线较低的海马体积相关(β=-0.27，p=0.001)，淀粉样蛋白沉积更大(β=0.48，p=0.001)，海马2年下降（β=-0.27，p=0.01），灰质总体积（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)，与对照组相比,AD-GRS较高的干预组PiB综合评分增加较少(β=-0.60,p=0.03).
结论：AD-GRS和APOE4可能对淀粉样蛋白的潜在干预作用有不同的影响，也就是说,与低风险组(APOE)相比，高风险组(AD-GRS)的积累较少。
结论：神经影像学和AD遗传学在多领域生活方式干预中的首次研究。对脑淀粉样蛋白沉积的可能干预作用可能依赖于遗传风险。AD-GRS和APOE4等位基因在干预过程中可能对淀粉样蛋白有不同的影响。
方法：1260名未患痴呆的老年高危人群随机接受多领域生活方式干预或健康建议。N=126名参与者接受了磁共振成像（MRI），和N=47正电子发射断层扫描(PET)扫描(匹兹堡CompundB[PiB]，氟脱氧葡萄糖）在基线；N=107和N=38重复2年扫描。
结果：APOE4等位基因，但不是AD-GRS,与基线较低的海马体积相关(β=-0.27，p=0.001)，淀粉样蛋白沉积更大(β=0.48，p=0.001)，海马2年下降（β=-0.27，p=0.01），灰质总体积（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)，与对照组相比,AD-GRS较高的干预组PiB综合评分增加较少(β=-0.60,p=0.03).
结论：AD-GRS和APOE4可能对淀粉样蛋白的潜在干预作用有不同的影响，也就是说,与低风险组(APOE)相比，高风险组(AD-GRS)的积累较少。
结论：神经影像学和AD遗传学在多领域生活方式干预中的首次研究。对脑淀粉样蛋白沉积的可能干预作用可能依赖于遗传风险。AD-GRS和APOE4等位基因在干预过程中可能对淀粉样蛋白有不同的影响。
