Department of Psychiatry, University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
JAMA. 2011 Jan 19;305(3):261-6. doi: 10.1001/jama.2010.1995.
Lower plasma β-amyloid 42 and 42/40 levels have been associated with incident dementia, but results are conflicting and few have investigated cognitive decline among elders without dementia.
To determine if plasma β-amyloid is associated with cognitive decline and if this association is modified by measures of cognitive reserve.
DESIGN, SETTING, AND PARTICIPANTS: We studied 997 black and white community-dwelling older adults from Memphis, Tennessee, and Pittsburgh, Pennsylvania, who were enrolled in the Health ABC Study, a prospective observational study begun in 1997-1998 with 10-year follow-up in 2006-2007. Participant mean age was 74.0 (SD, 3.0) years; 55.2% (n = 550) were female; and 54.0% (n = 538) were black.
Association of near-baseline plasma β-amyloid levels (42 and 42/40 measured in 2010) and repeatedly measured Modified Mini-Mental State Examination (3MS) results.
Low β-amyloid 42/40 level was associated with greater 9-year 3MS cognitive decline (lowest β-amyloid tertile: mean change in 3MS score, -6.59 [95% confidence interval [CI], -5.21 to -7.67] points; middle tertile: -6.16 [95% CI, -4.92 to -7.32] points; and highest tertile: -3.60 [95% CI, -2.27 to -4.73] points; P < .001). Results were similar after multivariate adjustment for age, race, education, diabetes, smoking, and apolipoprotein E [APOE ] e4 status and after excluding the 72 participants with incident dementia. Measures of cognitive reserve modified this association whereby among those with high reserve (at least a high school diploma, higher than sixth-grade literacy, or no APOE e4 allele), β-amyloid 42/40 was less associated with multivariate adjusted 9-year decline. For example, among participants with less than a high school diploma, the 3MS score decline was -8.94 (95% CI, -6.94 to -10.94) for the lowest tertile compared with -4.45 (95% CI, -2.31 to -6.59) for the highest tertile, but for those with at least a high school diploma, 3MS score decline was -4.60 (95% CI,-3.07 to -6.13) for the lowest tertile and -2.88 (95% CI,-1.41 to -4.35) for the highest tertile (P = .004 for interaction). Interactions were also observed for literacy (P = .005) and for APOE e4 allele (P = .02).
Lower plasma β-amyloid 42/40 is associated with greater cognitive decline among elderly persons without dementia over 9 years, and this association is stronger among those with low measures of cognitive reserve.
较低的血浆β-淀粉样蛋白 42 和 42/40 水平与痴呆症的发生有关，但结果存在矛盾，并且很少有研究调查没有痴呆症的老年人的认知能力下降。
确定血浆β-淀粉样蛋白是否与认知能力下降有关，以及这种关联是否受认知储备措施的影响。
设计、地点和参与者：我们研究了来自田纳西州孟菲斯和宾夕法尼亚州匹兹堡的 997 名黑人和白人社区居住的老年人，他们参加了健康 ABC 研究，这是一项前瞻性观察性研究，于 1997-1998 年开始，2006-2007 年进行了 10 年随访。参与者的平均年龄为 74.0（标准差，3.0）岁；55.2%（n=550）为女性；54.0%（n=538）为黑人。
近基线血浆β-淀粉样蛋白水平（2010 年测量的 42 和 42/40）与反复测量的改良迷你精神状态检查（3MS）结果的关联。
低β-淀粉样蛋白 42/40 水平与 9 年 3MS 认知下降有关（最低β-淀粉样蛋白三分位组：3MS 评分的平均变化，-6.59[95%置信区间（CI），-5.21 至-7.67]点；中间三分位组：-6.16[95%CI，-4.92 至-7.32]点；最高三分位组：-3.60[95%CI，-2.27 至-4.73]点；P<.001）。在对年龄、种族、教育程度、糖尿病、吸烟和载脂蛋白 E[APOE]e4 状态进行多变量调整后，以及在排除 72 名发生痴呆的参与者后，结果仍然相似。认知储备的衡量标准改变了这种关联，即对于储备较高的人群（至少有高中文凭、高于六年级的读写能力或没有 APOE e4 等位基因），β-淀粉样蛋白 42/40 与多变量调整后的 9 年下降的相关性较低。例如，在未完成高中学业的参与者中，最低三分位组的 3MS 评分下降为-8.94（95%CI，-6.94 至-10.94），而最高三分位组为-4.45（95%CI，-2.31 至-6.59），但对于至少有高中文凭的参与者，最低三分位组的 3MS 评分下降为-4.60（95%CI，-3.07 至-6.13），而最高三分位组为-2.88（95%CI，-1.41 至-4.35）（P=0.004 交互作用）。也观察到了与读写能力（P=0.005）和 APOE e4 等位基因（P=0.02）的交互作用。
在没有痴呆的老年人中，较低的血浆β-淀粉样蛋白 42/40 与 9 年内的认知能力下降有关，并且这种关联在认知储备较低的人群中更强。
