生物定义的阿尔茨海默病与年龄、性别、ε4 及认知障碍的关系频率。
Frequency of Biologically Defined Alzheimer Disease in Relation to Age, Sex, ε4, and Cognitive Impairment.
机构信息
From the Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Hospital (J.T., T.A.P., A.L.B., C.T., M.S., M.C., F.L., M.S.K., G.B., T.W., J.F.-A., S.G., P.R.-N.), and the Departments of Neurology and Neurosurgery (J.T., T.A.P., A.L.B., C.T., M.C., F.L., M.S.K., G.B., T.W., J.F.-A., J.-P.S., P.V., S.G., P.R.-N.), Psychiatry (S.G., P.R.-N.), Radiochemistry (G.M.), and Epidemiology and Biostatistics (P.S.-C.), McGill University, Montreal; and Montreal Neurological Institute (J.T., T.A.P., A.L.B., C.T., F.L., M.S.K., G.B., T.W., J.F.-A., G.M., J.-P.S., P.R.-N.), Canada.
出版信息
Neurology. 2021 Feb 16;96(7):e975-e985. doi: 10.1212/WNL.0000000000011416. Epub 2020 Dec 21.
OBJECTIVE
To assess the frequency of biologically defined Alzheimer disease (AD) in relation to age, sex, ε4, and clinical diagnosis in a prospective cohort study evaluated with amyloid-PET and tau-PET.
METHODS
We assessed cognitively unimpaired (CU) elderly (n = 166), patients with amnestic mild cognitive impairment (n = 77), and patients with probable AD dementia (n = 62) who underwent evaluation by dementia specialists and neuropsychologists in addition to amyloid-PET with [F]AZD4694 and tau-PET with [F]MK6240. Individuals were grouped according to their AD biomarker profile. Positive predictive value for biologically defined AD was assessed in relation to clinical diagnosis. Frequency of AD biomarker profiles was assessed using logistic regressions with odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
The clinical diagnosis of probable AD dementia demonstrated good agreement with biologically defined AD (positive predictive value 85.2%). A total of 7.88% of CU were positive for both amyloid-PET and tau-PET. Frequency of biologically defined AD increased with age (OR 1.14; < 0.0001) and frequency of ε4 allele carriers (single ε4: OR 3.82; < 0.0001; double ε4: OR 17.55, < 0.0001).
CONCLUSION
Whereas we observed strong, but not complete, agreement between clinically defined probable AD dementia and biomarker positivity for both β-amyloid and tau, we also observed that biologically defined AD was not rare in CU elderly. Abnormal tau-PET was almost exclusively observed in individuals with abnormal amyloid-PET. Our results highlight that even in tertiary care memory clinics, detailed evaluation by dementia specialists systematically underestimates the frequency of biologically defined AD and related entities.
CLASSIFICATION OF EVIDENCE
This study provides Class I evidence that biologically defined AD (abnormal amyloid PET and tau PET) was observed in 85.2% of people with clinically defined AD and 7.88% of CU elderly.
目的
在一项前瞻性队列研究中，评估生物定义的阿尔茨海默病（AD）与年龄、性别、ε4 和临床诊断的关系，该研究使用淀粉样蛋白-PET 和 tau-PET 进行评估。
方法
我们评估了认知正常的老年人（n=166）、有遗忘性轻度认知障碍（n=77）和可能患有 AD 痴呆的患者（n=62），这些患者除了接受淀粉样蛋白-PET 与[F]AZD4694 和 tau-PET 与[F]MK6240 评估外，还由痴呆专家和神经心理学家进行评估。根据他们的 AD 生物标志物特征对个体进行分组。在与临床诊断相关的情况下，评估生物定义的 AD 的阳性预测值。使用逻辑回归评估 AD 生物标志物特征的频率，使用比值比（OR）和 95%置信区间（CI）。
结果
可能患有 AD 痴呆的临床诊断与生物定义的 AD 具有良好的一致性（阳性预测值 85.2%）。共有 7.88%的认知正常者对淀粉样蛋白-PET 和 tau-PET 均呈阳性。生物定义的 AD 的频率随着年龄的增加而增加（OR 1.14；<0.0001）和ε4 等位基因携带者的频率增加（单 ε4：OR 3.82；<0.0001；双 ε4：OR 17.55，<0.0001）。
结论
虽然我们观察到临床上定义的可能患有 AD 痴呆与β-淀粉样蛋白和 tau 的生物标志物阳性之间存在强烈但不完全的一致性，但我们也观察到认知正常的老年人中生物定义的 AD 并不罕见。异常 tau-PET 几乎仅在异常淀粉样蛋白-PET 的个体中观察到。我们的结果强调，即使在三级保健记忆诊所中，由痴呆专家进行的详细评估也会系统地低估生物定义的 AD 和相关实体的频率。
证据分类
本研究提供了 I 级证据，表明临床上定义的 AD（异常淀粉样蛋白 PET 和 tau PET）在临床上定义的 AD 患者中占 85.2%，在认知正常的老年人中占 7.88%。
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