β-淀粉样蛋白水平与正常老年人的临床进展和纵向认知变化的关系。
Association of β-Amyloid Level, Clinical Progression, and Longitudinal Cognitive Change in Normal Older Individuals.
机构信息
From Austin Health (L.M.v.d.K., T.T., V.D., R.S.M., S.B., F.L., S.S., V.L.V., C.C.R.); CSIRO (S.C.B., V.D.), Melbourne; CSIRO (P.B., J.F., O.S.), Brisbane; The Florey Institute of Neuroscience and Mental Health (Y.Y.L., C.F., J.R., P.M., C.L.M.), Melbourne; University of Melbourne (T.T., D.A., C.L.M., V.L.V., C.C.R.); Edith Cowan University (S.M.L., S.R.R.-S., R.N.M.), Perth, Australia; and Washington University (S.S.), St. Louis, MO.
出版信息
Neurology. 2021 Feb 2;96(5):e662-e670. doi: 10.1212/WNL.0000000000011222. Epub 2020 Nov 12.
OBJECTIVE
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.
METHODS
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.
RESULTS
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; < 0.05), for high was 7.0 (95% CI 3.7-13.3; < 0.001), and for very high was 11.4 (95% CI 5.1-25.8; < 0.001). Decline in cognitive composite score was minimal in the moderate group (-0.02 SD/year, = 0.05), while the high and very high declined substantially (high -0.08 SD/year, < 0.001; very high -0.35 SD/year, < 0.001).
CONCLUSION
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.
目的
确定β-淀粉样蛋白（Aβ）水平对向轻度认知障碍（MCI）或痴呆进展的风险以及认知正常（CN）老年人的纵向认知变化的影响。
方法
所有纳入澳大利亚成像生物标志物和生活方式研究的具有 Aβ PET 和≥3 年随访的 CN（n=534；年龄 72±6 岁；27% Aβ阳性；随访 5.3±1.7 年）。使用标准化的 0-100 百分位标度来划分 Aβ 水平：<15 CL 阴性，15-25 CL 不确定，26-50 CL 中度，51-100 CL 高，>100 CL 极高，注意>25 CL 近似于阳性扫描。使用 Cox 比例风险分析和线性混合效应模型评估进展和认知下降的风险。
结果
63%的 Aβ 水平为阴性，10%为不确定，10%为中度，14%为高，3%为极高。57 人（11%）进展为 MCI 或痴呆。与 Aβ 阴性相比，Aβ 中度的进展风险比为 3.2（95%置信区间[CI]1.3-7.6；<0.05），Aβ 高的进展风险比为 7.0（95% CI 3.7-13.3；<0.001），Aβ 极高的进展风险比为 11.4（95% CI 5.1-25.8；<0.001）。中度组的认知综合评分下降最小（-0.02 SD/年，=0.05），而高组和极高组的下降幅度较大（高组-0.08 SD/年，<0.001；极高组-0.35 SD/年，<0.001）。
结论
在 5 年内，认知正常老年人向 MCI 或痴呆发展的风险与 PET 上的 Aβ 水平相关，如果 Aβ 阴性为 5%，如果 Aβ 阳性但在 26-50 CL 之间则为 25%，如果在 51-100 CL 之间则为 12%，如果>100 CL 则为 28%，如果>100 CL 则为 50%。这些信息可能对痴呆风险咨询和辅助设计临床前 AD 试验有用。
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