Predicting Cognitive Decline for Non-Demented Adults with High Burden of Tau Pathology, Independent of Amyloid Status

IF 4.3 Q2 BUSINESS
H.-S. Wu, L. Li, Q.-Q. Sun, C.-C. Tan, L. Tan, Wei Xu
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引用次数: 0

Abstract

Background

Abnormal tau proteins are independent contributors to cognitive impairment. Nevertheless, not all individuals exposed to high-level tau pathology will develop cognitive dysfunction. We aimed to construct a model to predict cognitive trajectory for this high-risk population.

Method

Longitudinal data of 181 non-demented adults (mean age= 73.1; female= 45%), who were determined to have high cerebral burden of abnormal tau by cerebrospinal fluid (CSF) measurements of phosphorylated tau (ptau181) or total tau, were derived from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Cognitive decline was defined as Mini-Mental State Examination scores decline ≥ 3 over three years. A predictive nomogram was constructed using stepwise backward regression method. The discrimination, calibration, and clinical usefulness of the nomogram were evaluated. The model was validated in another 189 non-demented adults via a cross-sectional set (n=149, mean age = 73.9, female = 51%) and a longitudinal set (n= 40, mean age = 75, female = 48%). Finally, the relationships of the calculated risk scores with cognitive decline and risk of Alzheimer’s disease were examined during an extended 8-year follow-up.

Result

Lower volume of hippocampus (odds ratio [OR] = 0.37, p< 0.001), lower levels of CSF sTREM2 (OR = 0.76, p = 0.003), higher scores of Alzheimer’s Disease Assessment Scale-Cognitive (OR = 1.15, p = 0.001) and Functional Activities Questionnaire (OR = 1.16, p = 0.016), and number of APOE ε4 (OR = 1.88, p = 0.039) were associated with higher risk of cognitive decline independent of the amyloid status and were included in the final model. The nomogram had an area of under curve (AUC) value of 0.91 for training set, 0.93 for cross-sectional validation set, and 0.91 for longitudinal validation set. Over the 8-year follow-up, the high-risk group exhibited faster cognitive decline (p< 0.001) and a higher risk of developing Alzheimer’s dementia (HR= 6.21, 95% CI= 3.61–10.66, p< 0.001).

Conclusion

APOE ε4 status, brain reserve capability, neuroinflammatory marker, and neuropsychological scores can help predict cognitive decline in non-demented adults with high burden of tau pathology, independent of the presence of amyloid pathology.

Abstract Image

与淀粉样蛋白状态无关,预测Tau病理学负担较重的非痴呆成人的认知能力衰退情况
背景异常的 tau 蛋白是造成认知障碍的独立因素。然而,并非所有暴露于高水平 tau 病理学的人都会出现认知功能障碍。我们从阿尔茨海默病神经影像学倡议(ADNI)数据库中获得了181名非痴呆成年人(平均年龄=73.1岁;女性=45%)的纵向数据,这些人通过脑脊液(CSF)中磷酸化tau(ptau181)或总tau的测量结果被确定为大脑中存在大量异常tau。认知能力下降的定义是三年内迷你精神状态检查评分下降≥3分。采用逐步回归法构建了预测提名图。对提名图的区分度、校准和临床实用性进行了评估。该模型在另外 189 名非痴呆成人中进行了验证,包括横断面组(n=149,平均年龄=73.9,女性=51%)和纵断面组(n=40,平均年龄=75,女性=48%)。最后,在长达 8 年的随访过程中,对计算出的风险评分与认知能力下降和阿尔茨海默病风险之间的关系进行了研究。结果 海马体积较小(几率比 [OR] = 0.37,p< 0.001),CSF sTREM2 水平较低(OR = 0.76,p = 0.003)、较高的阿尔茨海默病评估量表-认知评分(OR = 1.15,p = 0.001)和功能活动问卷(OR = 1.16,p = 0.016)以及 APOE ε4(OR = 1.88,p = 0.039)与较高的认知能力下降风险相关,且与淀粉样蛋白状态无关,并被纳入最终模型。训练集的提名图曲线下面积(AUC)值为0.91,横断面验证集为0.93,纵向验证集为0.91。结论APOE ε4状态、脑储备能力、神经炎症标志物和神经心理学评分有助于预测具有高tau病理负担的非痴呆成人的认知能力下降,而与是否存在淀粉样病理无关。
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来源期刊
The Journal of Prevention of Alzheimer's Disease
The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health
CiteScore
9.20
自引率
0.00%
发文量
0
期刊介绍: The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
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