From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Neurology. 2014 May 20;82(20):1760-7. doi: 10.1212/WNL.0000000000000431. Epub 2014 Apr 18.
To examine whether β-amyloid (Aβ) and APOE ε4 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN).
Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the contributions of APOE ε4 and Aβ on longitudinal change over a median of 1.49 years were examined. Cognitive decline was assessed with the Mini-Mental State Examination (MMSE) and Logical Memory (immediate and delayed recall scores).
High Aβ participants were more likely to be APOE ε4+ than low Aβ participants. CNs who were both high Aβ and APOE ε4+ showed greater decline in Logical Memory immediate recall (p < 0.087), Logical Memory delayed recall (p < 0.024), and MMSE (p < 0.034) compared to all other groups (low Aβ/APOE ε4-, low Aβ/APOE ε4+, and high Aβ/APOE ε4-). No other pairwise contrast was significant for any cognitive measure.
Clinically normal individuals who are APOE ε4+ and have high Aβ showed the highest cognitive decline. These results suggest that Aβ and APOE ε4 are not redundant contributors of decline in aging but rather interact to promote decline during the short follow-up period examined in this study. Longer follow-up periods will be essential to fully elucidate the influence of Alzheimer disease risk factors on cognitive decline in aging.
探讨β-淀粉样蛋白（Aβ）和 APOE ε4 状态是否独立或相互作用影响临床正常老年人（CN）的纵向认知衰退。
综合了 3 项观察性队列研究（哈佛衰老大脑研究、阿尔茨海默病神经影像学倡议和澳大利亚影像学生物标志物和生活方式衰老研究）中 490 名 CN 的数据（中位年龄=75.0 岁，女性 255 名），并考察了 APOE ε4 和 Aβ 对中位随访时间 1.49 年的纵向变化的影响。采用简易精神状态检查（MMSE）和逻辑记忆（即时和延迟回忆评分）评估认知下降。
高 Aβ 组更有可能为 APOE ε4+，而低 Aβ 组则不然。与其他所有组（低 Aβ/APOE ε4-、低 Aβ/APOE ε4+和高 Aβ/APOE ε4-）相比，高 Aβ 和 APOE ε4+的 CN 逻辑记忆即时回忆（p<0.087）、逻辑记忆延迟回忆（p<0.024）和 MMSE（p<0.034）下降更为显著。对于任何认知测量，没有其他成对比较有统计学意义。
APOE ε4+且 Aβ 水平高的临床正常个体认知下降最明显。这些结果表明，Aβ 和 APOE ε4 并不是衰老过程中认知下降的冗余因素，而是相互作用，在本研究的短期随访中促进认知下降。更长的随访时间对于充分阐明阿尔茨海默病危险因素对衰老过程中认知下降的影响至关重要。
