PDF(Pubmed)
Abstract：
Amyloid beta (Aβ), tau, and neurodegeneration jointly with the Alzheimer\'s disease (AD) risk factors affect the severity of clinical symptoms and disease progression.
Within 248 Aβ-positive elderly with and without cognitive impairment and dementia, partial least squares structural equation pathway modeling was used to assess the direct and indirect effects of imaging biomarkers (global Aβ-positron emission tomography [PET] uptake, regional tau-PET uptake, and regional magnetic resonance imaging-based atrophy) and risk-factors (age, sex, education, apolipoprotein E [APOE], and white-matter lesions) on cross-sectional cognitive impairment and longitudinal cognitive decline.
Sixteen percent of variance in cross-sectional cognitive impairment was accounted for by Aβ, 46% to 47% by tau, and 25% to 29% by atrophy, although 53% to 58% of total variance in cognitive impairment was explained by incorporating mediated and direct effects of AD risk factors. The Aβ-tau-atrophy pathway accounted for 50% to 56% of variance in longitudinal cognitive decline while Aβ, tau, and atrophy independently explained 16%, 46% to 47%, and 25% to 29% of the variance, respectively.
These findings emphasize that treatments that remove Aβ and completely stop downstream effects on tau and neurodegeneration would only be partially effective in slowing of cognitive decline or reversing cognitive impairment.
Within 248 Aβ-positive elderly with and without cognitive impairment and dementia, partial least squares structural equation pathway modeling was used to assess the direct and indirect effects of imaging biomarkers (global Aβ-positron emission tomography [PET] uptake, regional tau-PET uptake, and regional magnetic resonance imaging-based atrophy) and risk-factors (age, sex, education, apolipoprotein E [APOE], and white-matter lesions) on cross-sectional cognitive impairment and longitudinal cognitive decline.
Sixteen percent of variance in cross-sectional cognitive impairment was accounted for by Aβ, 46% to 47% by tau, and 25% to 29% by atrophy, although 53% to 58% of total variance in cognitive impairment was explained by incorporating mediated and direct effects of AD risk factors. The Aβ-tau-atrophy pathway accounted for 50% to 56% of variance in longitudinal cognitive decline while Aβ, tau, and atrophy independently explained 16%, 46% to 47%, and 25% to 29% of the variance, respectively.
These findings emphasize that treatments that remove Aβ and completely stop downstream effects on tau and neurodegeneration would only be partially effective in slowing of cognitive decline or reversing cognitive impairment.
摘要：
淀粉样蛋白β(Aβ),tau,神经变性与阿尔茨海默病(AD)危险因素共同影响临床症状的严重程度和疾病进展。
在248名有或没有认知障碍和痴呆的Aβ阳性老年人中，偏最小二乘结构方程路径模型用于评估成像生物标志物的直接和间接影响(全球Aβ-正电子发射断层扫描[PET]摄取，区域tau-PET吸收，和基于区域磁共振成像的萎缩)和风险因素(年龄，性别,教育,载脂蛋白E[APOE]，和白质病变）的横断面认知障碍和纵向认知功能下降。
横断面认知障碍的16%的差异是由Aβ引起的，46%到47%的tau，25%到29%的萎缩，虽然53%~58%的认知损害总变异是通过纳入AD危险因素的介导效应和直接效应来解释的.Aβ-tau-萎缩通路占纵向认知功能下降的50%-56%,tau,萎缩独立解释了16%，46%到47%，和25%到29%的方差，分别。
这些发现强调，去除Aβ并完全停止对tau和神经变性的下游影响的治疗仅在减缓认知下降或逆转认知障碍方面部分有效。
在248名有或没有认知障碍和痴呆的Aβ阳性老年人中，偏最小二乘结构方程路径模型用于评估成像生物标志物的直接和间接影响(全球Aβ-正电子发射断层扫描[PET]摄取，区域tau-PET吸收，和基于区域磁共振成像的萎缩)和风险因素(年龄，性别,教育,载脂蛋白E[APOE]，和白质病变）的横断面认知障碍和纵向认知功能下降。
横断面认知障碍的16%的差异是由Aβ引起的，46%到47%的tau，25%到29%的萎缩，虽然53%~58%的认知损害总变异是通过纳入AD危险因素的介导效应和直接效应来解释的.Aβ-tau-萎缩通路占纵向认知功能下降的50%-56%,tau,萎缩独立解释了16%，46%到47%，和25%到29%的方差，分别。
这些发现强调，去除Aβ并完全停止对tau和神经变性的下游影响的治疗仅在减缓认知下降或逆转认知障碍方面部分有效。
