From the Department of Radiology (B.S.R.) and Division of Mental Health of Older Adults, Department of Psychiatry and Psychotherapy (B.S.R., S.M., R.P.), University Hospital, Ludwig-Maximilians-Universität München, Nussbaumstr 7, 80336 Munich, Germany; Department of Psychiatry, University of British Columbia, Vancouver, Canada (F.G.); German Center for Neurodegenerative Diseases Munich, Germany (R.P.); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (R.P.); and Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, England (R.P.).
Radiology. 2020 Jul;296(1):134-142. doi: 10.1148/radiol.2020191904. Epub 2020 May 5.
Background Growing evidence indicates an association between cerebral microhemorrhages (MHs) and amyloid β accumulation in Alzheimer disease (AD), but to the knowledge of the authors the association with tau burden is unknown. Purpose To investigate the association between cerebral MH load and tau pathologic structure measured in healthy older individuals and individuals along the AD spectrum, stratified by using the A (amyloid β)/T (tau)/N (neurodegeneration) biomarker classification system. Materials and methods In this prospective cohort study, participants from the AD Neuroimaging Initiative were included (healthy control participants, participants with mild cognitive impairment, and participants with AD dementia; data from October 2005 to January 2019). T2*-weighted gradient-echo MRI was performed to quantify MH, fluorine 18 (F) flortaucipir (AV-1451) PET was performed to quantify tau, and F-florbetaben/F- florbetapir (AV45) PET was performed to quantify amyloid β to study associations of MH with regional and global tau and amyloid β load. Associations with cerebrospinal fluid (CSF) biomarkers (amyloid β1-42, total tau, phosphorylated tau 181) were also assessed. Analysis of covariance and Spearman rank correlation test for cross-sectional analysis and Wilcoxon signed rank test for longitudinal analyses were used, controlling for multiple comparisons (Bonferroni significance threshold, < .008). Results Evaluated were 343 participants (mean age, 75 years ± 7; 186 women), including 205 participants who were A-TN- (mean age, 73 years ± 7; 115 women), 80 participants who were A+TN- (mean age, 76 years ± 7; 38 women), and 58 participants who were A+TN+ (mean age, 77 ± 8; 34 women). MH count was associated with global (Spearman ρ = 0.27; = .004) and frontal (ρ = 0.27; = .005) amyloid β load and global tau load (ρ = 0.31; = .001). In a longitudinal analysis, MH count increased significantly over approximately 5 years in the entire cohort (T-1, 81 [range, 0-6 participants]; T0, 214 [range, 0-58 participants]; < .001), in A+TN+ (T-1, 20 [range, 0-5 participants]; T0, 119 [range, 1-58 participants]; < .001), A+TN- (T-1, 31 [range, 0-6 participants]; T0, 43 [range, 0-8 participants]; = .03), and A-TN- (T-1, 30 [range, 0-4 participants]; T0, 52 [range, 0-6 participants]; = .007). A higher MH count was associated with higher future global (ρ = 0.29; = .008) and parietal (ρ = 0.31; = .005) amyloid β and parietal tau load (ρ = 0.31; = .005). Conclusion Cerebral microhemorrhage load is associated spatially with tau accumulation, both cross-sectionally and longitudinally. © RSNA, 2020
背景 越来越多的证据表明脑微出血 (MHs) 与阿尔茨海默病 (AD) 中的淀粉样 β 积聚之间存在关联，但作者认为其与 tau 负担的关联尚不清楚。目的 研究在健康老年人和 AD 谱个体中，脑 MH 负荷与 tau 病理结构之间的关系，使用 A (淀粉样 β)/T (tau)/N (神经退行性变) 生物标志物分类系统进行分层。材料与方法 本前瞻性队列研究纳入了 AD 神经影像学倡议的参与者（健康对照参与者、轻度认知障碍参与者和 AD 痴呆症参与者；数据采集时间为 2005 年 10 月至 2019 年 1 月）。采用 T2*-加权梯度回波 MRI 定量 MH，氟 18 (F) 氟替卡培 (AV-1451) PET 定量 tau，F-氟比他滨/F-氟比卡培 (AV45) PET 定量淀粉样 β，以研究 MH 与区域和全局 tau 以及淀粉样 β 负荷的相关性。还评估了与脑脊液 (CSF) 生物标志物（淀粉样 β1-42、总 tau、磷酸化 tau 181）的相关性。使用协方差分析和 Spearman 秩相关检验进行横断面分析，Wilcoxon 符号秩检验进行纵向分析，同时控制了多重比较（Bonferroni 显著性阈值，<.008）。结果 共评估了 343 名参与者（平均年龄 75 岁±7；186 名女性），其中 205 名参与者为 A-TN-（平均年龄 73 岁±7；115 名女性），80 名参与者为 A+TN-（平均年龄 76 岁±7；38 名女性），58 名参与者为 A+TN+（平均年龄 77±8；34 名女性）。MH 计数与全局（Spearman ρ = 0.27； =.004）和额部（ρ = 0.27； =.005）淀粉样 β 负荷以及全局 tau 负荷呈正相关（ρ = 0.31； =.001）。在一项纵向分析中，整个队列的 MH 计数在大约 5 年内显著增加（T-1，81[范围，0-6 名参与者]；T0，214[范围，0-58 名参与者]；<.001），在 A+TN+（T-1，20[范围，0-5 名参与者]；T0，119[范围，1-58 名参与者]；<.001）、A+TN-（T-1，31[范围，0-6 名参与者]；T0，43[范围，0-8 名参与者]；=.03）和 A-TN-（T-1，30[范围，0-4 名参与者]；T0，52[范围，0-6 名参与者]；=.007）。更高的 MH 计数与未来的全局（ρ = 0.29； =.008）和顶叶（ρ = 0.31； =.005）淀粉样 β 以及顶叶 tau 负荷呈正相关（ρ = 0.31； =.005）。结论 脑微出血负荷与 tau 积聚存在空间相关性，无论是在横断面还是纵向研究中。
