Division of Epidemiology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
Neurology. 2012 Oct 9;79(15):1570-7. doi: 10.1212/WNL.0b013e31826e2696. Epub 2012 Sep 12.
Secondary prevention trials in subjects with preclinical Alzheimer disease may require documentation of brain amyloidosis. The identification of inexpensive and noninvasive screening variables that can identify individuals who have significant amyloid accumulation would reduce screening costs.
A total of 483 cognitively normal (CN) individuals, aged 70-92 years, from the population-based Mayo Clinic Study of Aging, underwent Pittsburgh compound B (PiB)-PET imaging. Logistic regression determined whether age, sex, APOE genotype, family history, or cognitive performance was associated with odds of a PiB retention ratio >1.4 and >1.5. Area under the receiver operating characteristic curve (AUROC) evaluated the discrimination between PiB-positive and -negative subjects. For each characteristic, we determined the number needed to screen in each age group (70-79 and 80-89) to identify 100 participants with PiB >1.4 or >1.5.
A total of 211 (44%) individuals had PiB >1.4 and 151 (31%) >1.5. In univariate and multivariate models, discrimination was modest (AUROC ∼0.6-0.7). Multivariately, age and APOE best predicted odds of PiB >1.4 and >1.5. Subjective memory complaints were similar to cognitive test performance in predicting PiB >1.5. Indicators of PiB positivity varied with age. Screening APOE ε4 carriers alone reduced the number needed to screen to enroll 100 subjects with PIB >1.5 by 48% in persons aged 70-79 and 33% in those aged 80-89.
Age and APOE genotype are useful predictors of the likelihood of significant amyloid accumulation, but discrimination is modest. Nonetheless, these results suggest that inexpensive and noninvasive measures could significantly reduce the number of CN individuals needed to screen to enroll a given number of amyloid-positive subjects.
在有临床前阿尔茨海默病的受试者中进行二级预防试验可能需要记录脑淀粉样蛋白。确定便宜且非侵入性的筛选变量，可以识别出具有显著淀粉样蛋白堆积的个体，将降低筛选成本。
总共纳入了 483 名认知正常（CN）个体，年龄在 70-92 岁之间，来自基于人群的梅奥诊所老龄化研究，他们接受了匹兹堡复合物 B（PiB）-PET 成像。逻辑回归确定年龄、性别、APOE 基因型、家族史或认知表现是否与 PiB 保留率>1.4 和>1.5 的几率相关。接受者操作特征曲线下的面积（AUROC）评估了 PiB 阳性和阴性受试者之间的区分度。对于每个特征，我们确定了在每个年龄组（70-79 岁和 80-89 岁）中需要筛查的人数，以识别出 100 名 PiB>1.4 或>1.5 的参与者。
共有 211 名（44%）个体的 PiB>1.4，151 名（31%）个体的 PiB>1.5。在单变量和多变量模型中，区分度适中（AUROC ∼0.6-0.7）。在多变量模型中，年龄和 APOE 是预测 PiB>1.4 和>1.5 的最佳指标。主观记忆主诉与预测 PiB>1.5 的认知测试表现相似。PiB 阳性的指标随年龄而变化。单独筛查 APOE ε4 携带者可使 70-79 岁人群中需要筛查的人数减少 48%，使 80-89 岁人群中需要筛查的人数减少 33%，从而招募到 PiB>1.5 的 100 名受试者。
年龄和 APOE 基因型是淀粉样蛋白大量堆积可能性的有用预测指标，但区分度适中。尽管如此，这些结果表明，廉价且非侵入性的措施可能会显著减少筛选 CN 个体以招募给定数量的淀粉样蛋白阳性受试者所需的人数。
