From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I.), Psychiatry (O.L.L., J.T.B., W.E.K., H.J.A., A.D.C.), Psychology (J.T.B.), Neurosurgery (Y.C.), Epidemiology, Graduate School of Public Health (Y.C., L.H.K.), Radiology (C.M., J.P.), Pharmaceutical Sciences (C.M.), and Genetics (M.I.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Florida, Gainesville.
Neurology. 2018 May 22;90(21):e1920-e1928. doi: 10.1212/WNL.0000000000005549. Epub 2018 Apr 25.
To test the hypothesis that brain structural integrity (i.e., hippocampal [HIP] volume), white matter lesions (WMLs), and β-amyloid deposition are associated with long-term increased risk of incident dementia and mortality in 183 cognitively normal individuals and patients with mild cognitive impairment (MCI) aged 80 years and older.
All participants had a brain structural MRI scan and PET scan with C-labeled Pittsburgh compound B in 2009 and were reexamined yearly through 2015 (mean follow-up time 5.2 ± 1.3 years).
In the last evaluation through 2010-2015, 56 (31%) participants were cognitively normal, 67 (37%) had MCI, and 60 (33%) had dementia. Fifty-seven (31%) died during follow-up, and 20 (35%) developed dementia before their death. All 3 biomarkers were independent predictors of incident dementia in all participants. After adjusting for the risk of dying, amyloid deposition and WMLs remained strong predictors. Of the 60 participants with incident dementia, 54 (90%) had at least one imaging abnormality. Participants with no biomarker positivity had a very low risk of dementia (16%), while 75% of the participants with the 3 biomarkers progressed to dementia. HIP volume and β-amyloid deposition were associated with death only in participants with MCI.
This study showed the presence of more than one biomarker was a stronger long-term predictor of incident dementia than any biomarker alone. After adjusting for the risk of dying, amyloid deposition and WMLs were stronger predictors of dementia than HIP volume. The risk of dying during follow-up was associated with both neurodegeneration and amyloid deposition, especially in individuals with MCI.
验证假设，即脑结构完整性（即海马体[HIP]体积）、白质病变（WML）和β-淀粉样蛋白沉积与 183 名认知正常个体和 80 岁及以上轻度认知障碍（MCI）患者的长期痴呆和死亡风险增加相关。
所有参与者均于 2009 年进行了脑结构 MRI 扫描和 C 标记的匹兹堡化合物 B 的 PET 扫描，并在 2015 年之前每年进行复查（平均随访时间为 5.2±1.3 年）。
在 2010 年至 2015 年的最后一次评估中，56 名（31%）参与者认知正常，67 名（37%）患有 MCI，60 名（33%）患有痴呆。在随访期间有 57 名（31%）死亡，20 名（35%）在死亡前患有痴呆。所有 3 种生物标志物均为所有参与者发生痴呆的独立预测因素。在调整死亡风险后，淀粉样蛋白沉积和 WML 仍然是强有力的预测因素。在发生痴呆的 60 名参与者中，54 名（90%）至少有一种影像学异常。没有生物标志物阳性的参与者发生痴呆的风险非常低（16%），而 75%的有 3 种生物标志物的参与者进展为痴呆。HIP 体积和β-淀粉样蛋白沉积仅与 MCI 患者的死亡相关。
本研究表明，存在多种生物标志物比任何单一生物标志物更能长期预测痴呆的发生。在调整死亡风险后，淀粉样蛋白沉积和 WML 比 HIP 体积更能预测痴呆。随访期间的死亡风险与神经退行性变和淀粉样蛋白沉积都有关，尤其是在 MCI 患者中。
