Does accelerated cortical atrophy in aging, especially in areas vulnerable to early Alzheimer's disease (AD), unequivocally signify neurodegenerative disease or can it be part of normal aging? We addressed this in 3 ways. First, age trajectories of cortical thickness were delineated cross-sectionally (n = 1100) and longitudinally (n = 207). Second, effects of undetected AD on the age trajectories were simulated by mixing the sample with a sample of patients with very mild to moderate AD. Third, atrophy in AD-vulnerable regions was examined in older adults with very low probability of incipient AD based on 2-year neuropsychological stability, CSF Aβ(1-42) levels, and apolipoprotein ε4 negativity. Steady decline was seen in most regions, but accelerated cortical thinning in entorhinal cortex was observed across groups. Very low-risk older adults had longitudinal entorhinal atrophy rates similar to other healthy older adults, and this atrophy was predictive of memory change. While steady decline in cortical thickness is the norm in aging, acceleration in AD-prone regions does not uniquely signify neurodegenerative illness but can be part of healthy aging. The relationship between the entorhinal changes and changes in memory performance suggests that non-AD mechanisms in AD-prone areas may still be causative for cognitive reductions.

译文

:衰老中的皮质萎缩加速,特别是在容易患早老性阿尔茨海默氏病(AD)的地区,是否明确表示神经退行性疾病或它是否可以成为正常衰老的一部分?我们通过3种方式解决了这个问题。首先,在横截面(n = 1100)和纵向(n = 207)上划定了皮质厚度的年龄轨迹。其次,通过将样本与患有轻度至中度AD的患者样本混合来模拟未检测到的AD对年龄轨迹的影响。第三,根据2年的神经心理学稳定性,脑脊液Aβ(1-42)水平和载脂蛋白ε4阴性,检查了成年人AD弱势地区的萎缩,其发生AD的可能性非常低。在大多数地区都观察到稳定的下降,但是在各组中观察到内嗅皮层的皮层加速变薄。非常低风险的老年人的纵向内脏萎缩率与其他健康的老年人相似,并且该萎缩可预测记忆力的改变。尽管皮层厚度的持续下降是衰老的常态,但AD易发地区的加速并不唯一表示神经退行性疾病,而是健康衰老的一部分。内嗅变化与记忆性能变化之间的关系表明,AD易发地区的非AD机制可能仍然是导致认知能力下降的原因。

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