Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
J Alzheimers Dis. 2011;27(4):897-907. doi: 10.3233/JAD-2011-110782.
We sought to identify cognitive phenotypes for family/genetic studies of successful cognitive aging (SCA; maintaining intact cognitive functioning while living to late old age). We administered a battery of neuropsychological tests to nondemented nonagenarians (n = 65; mean age = 93.4 ± 3.0) and their offspring (n = 188; mean age = 66.4 ± 5.0) from the Central Valley of Costa Rica. After covarying for age, gender, and years of education, as necessary, heritability was calculated for cognitive functions at three pre-defined levels of complexity: specific neuropsychological functions (e.g., delayed recall, sequencing), three higher level cognitive domains (memory, executive functions, attention), and an overall neuropsychological summary. The highest heritability was for delayed recall (h² = 0.74, se = 0.14, p < 0.0001) but significant heritabilities involving memory were also observed for immediate recall (h² = 0.50), memory as a cognitive domain (h² = 0.53), and the overall neuropsychological summary (h² = 0.42). Heritabilities for sequencing (h² = 0.42), fluency (h² = 0.39), abstraction (h² = 0.36), and the executive functions cognitive domain (h² = 0.35) were also significant. In contrast, the attention domain and memory recognition were not significantly heritable in these families. Among the heritable specific cognitive functions, a strong pleiotropic effect (i.e., evidence that these may be influenced by the same gene or set of genes) for delayed and immediate recall was identified (bivariate statistic = 0.934, p < 0.0001) and more modest but significant effects were found for four additional bivariate relationships. The results support the heritability of good cognitive function in old age and the utilization of several levels of phenotypes, and they suggest that several measures involving memory may be especially useful for family/genetic studies of SCA.
我们试图确定认知表型,以进行成功认知老化(SCA;在活到老年时保持完整的认知功能)的家族/遗传研究。我们对来自哥斯达黎加中谷的 65 名非痴呆 90 岁以上老人(平均年龄=93.4±3.0)及其后代(188 名;平均年龄=66.4±5.0)进行了一系列神经心理学测试。在协方差年龄、性别和受教育年限后,在三个预先定义的复杂程度水平上计算了认知功能的遗传率:特定神经心理学功能(例如,延迟回忆、排序)、三个更高水平的认知领域(记忆、执行功能、注意力)和整体神经心理学综合评分。延迟回忆的遗传率最高(h²=0.74,se=0.14,p<0.0001),但即时回忆(h²=0.50)、记忆作为认知领域(h²=0.53)和整体神经心理学综合评分(h²=0.42)也观察到显著的记忆遗传率。排序(h²=0.42)、流畅性(h²=0.39)、抽象(h²=0.36)和执行功能认知领域(h²=0.35)的遗传率也具有统计学意义。相比之下,在这些家庭中,注意力领域和记忆识别没有显著的遗传性。在可遗传的特定认知功能中,发现延迟和即时回忆具有很强的多效性(即,这些可能受相同基因或一组基因影响的证据)(双变量统计量=0.934,p<0.0001),并且发现了另外四个双变量关系的适度但显著的影响。研究结果支持老年良好认知功能的遗传性以及利用多个表型水平,并且表明涉及记忆的几种措施可能特别有助于 SCA 的家族/遗传研究。