Association of β-Amyloid Level, Clinical Progression, and Longitudinal Cognitive Change in Normal Older Individuals.
Association of β-Amyloid Level, Clinical Progression, and Longitudinal Cognitive Change in Normal Older Individuals.
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DOI：
10.1212/wnl.0000000000011222
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发表时间：
2021-02-02
期刊：
影响因子：
9.9
通讯作者：
Rowe CC
中科院分区：
文献类型：
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作者：
van der Kall LM;Truong T;Burnham SC;Doré V;Mulligan RS;Bozinovski S;Lamb F;Bourgeat P;Fripp J;Schultz S;Lim YY;Laws SM;Ames D;Fowler C;Rainey-Smith SR;Martins RN;Salvado O;Robertson J;Maruff P;Masters CL;Villemagne VL;Rowe CC
确定β-淀粉样蛋白（Aβ）水平对认知正常（CN）老年人进展为轻度认知功能障碍（MCI）或痴呆的风险以及纵向认知变化的影响。纳入了来自澳大利亚成像生物标志物和生活方式研究（Aβ PET）和≥3年随访的所有CN（n = 534;年龄72 ± 6岁; 27% Aβ阳性;随访5.3 ± 1.7年）。使用标准化0-100 Centiloid量表划分Aβ水平：<15 CL阴性，15-25 CL不确定，26-50 CL中等，51-100 CL高，>100 CL非常高，注意>25 CL接近阳性扫描。采用考克斯比例风险分析和线性混合效应模型评估进展和认知能力下降的风险。63%的Aβ水平为阴性，10%不确定，10%中等，14%高，3%非常高。57例（11%）进展为MCI或痴呆。与阴性Aβ相比，中度Aβ进展的风险比为3.2（95%置信区间[CI] 1.3-7.6; p < 0.05），高度A β进展的风险比为7.0（95%CI 3.7-13.3; p < 0.001），非常高的风险比为11.4（95%CI 5.1-25.8; p < 0.001）。中度组的认知综合评分下降最小（-0.02 SD/年，p = 0.05），而高和非常高的下降幅度很大（高-0.08 SD/年，p < 0.001;非常高-0.35 SD/年，p < 0.001）。在老年CN中，5年以上MCI或痴呆的风险与PET上的Aβ水平相关，阴性为5%，阳性为25%，但范围从26-50 CL的12%到51-100 CL的28%和>100 CL的50%。这些信息可能有助于痴呆风险咨询和临床前AD试验的设计。
To determine the effect of β-amyloid (Aβ) level on progression risk to mild cognitive impairment (MCI) or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals. All CN from the Australian Imaging Biomarkers and Lifestyle study with Aβ PET and ≥3 years follow-up were included (n = 534; age 72 ± 6 years; 27% Aβ positive; follow-up 5.3 ± 1.7 years). Aβ level was divided using the standardized 0–100 Centiloid scale: <15 CL negative, 15–25 CL uncertain, 26–50 CL moderate, 51–100 CL high, >100 CL very high, noting >25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess risk of progression and cognitive decline. Aβ levels in 63% were negative, 10% uncertain, 10% moderate, 14% high, and 3% very high. Fifty-seven (11%) progressed to MCI or dementia. Compared to negative Aβ, the hazard ratio for progression for moderate Aβ was 3.2 (95% confidence interval [CI] 1.3–7.6; p < 0.05), for high was 7.0 (95% CI 3.7–13.3; p < 0.001), and for very high was 11.4 (95% CI 5.1–25.8; p < 0.001). Decline in cognitive composite score was minimal in the moderate group (−0.02 SD/year, p = 0.05), while the high and very high declined substantially (high −0.08 SD/year, p < 0.001; very high −0.35 SD/year, p < 0.001). The risk of MCI or dementia over 5 years in older CN is related to Aβ level on PET, 5% if negative vs 25% if positive but ranging from 12% if 26–50 CL to 28% if 51–100 CL and 50% if >100 CL. This information may be useful for dementia risk counseling and aid design of preclinical AD trials.