Department of Neurology, Boston University School of Medicine, B602, 72 East Concord Street, Boston, MA 02118, USA.
Neurology. 2009 Dec 15;73(24):2071-8. doi: 10.1212/WNL.0b013e3181c67833. Epub 2009 Dec 9.
Studies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort.
A total of 717 Framingham offspring (mean age: 59 +/- 8 years) were studied. In multivariate analyses, we compared offspring with and without verified parental dementia (and AD) for 1) performance on tests of memory, abstract reasoning, and cognitive flexibility, and 2) volumetric brain MRI measures of total cerebral brain volume (TCBV), hippocampal volume (HV), and white matter hyperintensity volume (WMHV), assessed cross-sectionally and longitudinally.
When testing the association of parental dementia and AD with baseline cognitive performance, we observed an interaction of parental dementia and AD with APOE epsilon4 status (p < 0.002). In APOE epsilon4 carriers only (n = 165), parental dementia was associated with poorer scores on tests of verbal memory (beta = -1.81 +/- 0.53, p < 0.001) and visuospatial memory (beta = -1.73 +/- 0.47, p < 0.001). These associations were stronger for parental AD (beta = -1.97 +/- 0.52, p < 0.001, beta = -1.95 +/- 0.48, p < 0.001), equivalent to 14-16 years of brain aging. Among APOE epsilon4 carriers, offspring of participants with dementia were also more likely to show an annual decline in TCBV in the top quartile (odds ratio = 4.67 [1.26-17.30], p = 0.02). Regardless of APOE epsilon4 status, participants with parental dementia were more likely to be in the highest quartile of decline in executive function test scores (odds ratio = 1.61 [1.02-2.53], p = 0.04).
Among middle-aged carriers of the APOE epsilon4 allele, parental dementia and Alzheimer disease were associated with poorer verbal and visuospatial memory and a higher rate of global brain atrophy.
常染色体显性阿尔茨海默病（AD）的研究表明，突变携带者在临床疾病发生前数十年就出现了结构和认知上的变化。然而，散发性痴呆患者的子女是否存在这种变化尚不清楚。我们在一个 2 代社区为基础的队列中，前瞻性地将经证实的父母痴呆症与子女的脑 MRI 和认知测试相关联。
共纳入 717 名弗雷明汉后代（平均年龄：59 +/- 8 岁）进行研究。在多变量分析中，我们比较了有和无经证实的父母痴呆症（包括 AD）的后代之间：1）记忆、抽象推理和认知灵活性测试的表现；2）横向和纵向评估全脑脑容量（TCBV）、海马体积（HV）和脑白质高信号体积（WMHV）的脑 MRI 测量值。
当我们检测父母痴呆症和 AD 与基线认知表现的相关性时，我们观察到父母痴呆症和 AD 与 APOE ε4 状态之间存在交互作用（p < 0.002）。仅在 APOE ε4 携带者中（n = 165），父母痴呆症与言语记忆测试（β = -1.81 +/- 0.53，p < 0.001）和视空间记忆测试（β = -1.73 +/- 0.47，p < 0.001）得分较差相关。这些关联在父母 AD 中更强（β = -1.97 +/- 0.52，p < 0.001，β = -1.95 +/- 0.48，p < 0.001），相当于大脑老化 14-16 年。在 APOE ε4 携带者中，患有痴呆症的参与者的后代 TCBV 每年也更有可能在前四分之一位下降（优势比 = 4.67 [1.26-17.30]，p = 0.02）。无论 APOE ε4 状态如何，父母有痴呆症的参与者在执行功能测试评分的最高四分位数中更有可能下降（优势比 = 1.61 [1.02-2.53]，p = 0.04）。
在携带 APOE ε4 等位基因的中年携带者中，父母痴呆症和阿尔茨海默病与言语和视空间记忆较差以及大脑整体萎缩速度较快有关。
