β-amyloid (Aβ) pathology is not always coupled with Alzheimer’s disease (AD) relevant cognitive decline. We assessed the accuracy of tau PET to identify Aβ(+) individuals who show prospective disease progression. 396 cognitively unimpaired and impaired individuals with baseline Aβ and tau PET and a follow-up of ≥ 2 years were selected from the Alzheimer’s Disease Neuroimaging Initiative dataset. The participants were dichotomously grouped based on either clinical conversion (i.e., change of diagnosis) or cognitive deterioration (fast (FDs) vs. slow decliners (SDs)) using data-driven clustering of the individual annual rates of cognitive decline. To assess cognitive decline in individuals with isolated Aβ(+) or absence of both Aβ and tau (T) pathologies, we investigated the prevalence of non-AD comorbidities and FDG PET hypometabolism patterns suggestive of AD. Baseline tau PET uptake was higher in Aβ(+)FDs than in Aβ(-)FD/SDs and Aβ(+)SDs, independently of baseline cognitive status. Baseline tau PET uptake identified MCI Aβ(+) Converters and Aβ(+)FDs with an area under the curve of 0.85 and 0.87 (composite temporal region of interest) respectively, and was linearly related to the annual rate of cognitive decline in Aβ(+) individuals. The T(+) individuals constituted largely a subgroup of those being Aβ(+) and those clustered as FDs. The most common biomarker profiles in FDs (n = 70) were Aβ(+)T(+) (n = 34, 49%) and Aβ(+)T(-) (n = 19, 27%). Baseline Aβ load was higher in Aβ(+)T(+)FDs (M = 83.03 ± 31.42CL) than in Aβ(+)T(-)FDs (M = 63.67 ± 26.75CL) (p-value = 0.038). Depression diagnosis was more prevalent in Aβ(+)T(-)FDs compared to Aβ(+)T(+)FDs (47% vs. 15%, p-value = 0.021), as were FDG PET hypometabolism pattern not suggestive of AD (86% vs. 50%, p-value = 0.039). Our findings suggest that high tau PET uptake is coupled with both Aβ pathology and accelerated cognitive decline. In cases of isolated Aβ(+), cognitive decline may be associated with changes within the AD spectrum in a multi-morbidity context, i.e., mixed AD.

β-淀粉样蛋白 (Aβ) 病理学并不总是与阿尔茨海默病 (AD) 相关的认知能力下降相关。我们评估了 tau PET 识别显示预期疾病进展的 Aβ(+) 个体的准确性。从阿尔茨海默病神经影像倡议数据集中选出了 396 名认知未受损和受损的个体，他们具有基线 Aβ 和 tau PET 且随访时间≥ 2 年。使用数据驱动的个体年度认知衰退率聚类，根据临床转化（即诊断改变）或认知恶化（快速（FD）与慢速衰退（SD））对参与者进行二分分组。为了评估患有孤立性 Aβ(+) 或同时缺乏 Aβ 和 tau (T) 病理的个体的认知能力下降，我们调查了非 AD 合并症的患病率和提示 AD 的 FDG PET 代谢低下模式。 Aβ(+)FD 的基线 tau PET 摄取高于 Aβ(-)FD/SD 和 Aβ(+)SD，与基线认知状态无关。基线 tau PET 摄取识别出 MCI Aβ(+) 转换器和 Aβ(+)FD，曲线下面积分别为 0.85 和 0.87（感兴趣的复合时间区域），并且与 Aβ 认知能力年下降率线性相关（ +) 个人。 T(+) 个体主要构成 Aβ(+) 个体和聚集为 FD 的个体的一个亚组。 FD 中最常见的生物标志物谱 ( n = 70) 是 Aβ(+)T(+) ( n = 34, 49%) 和 Aβ(+)T(-) ( n = 19, 27%)。 Aβ(+)T(+)FD (M = 83.03 ± 31.42CL) 中的基线 Aβ 负荷高于 Aβ(+)T(-)FD (M = 63.67 ± 26.75CL) ( p值 = 0.038)。与 Aβ(+)T(+)FD 相比，Aβ(+)T(-)FD 中抑郁症诊断更为普遍（47% vs. 15%， p值 = 0。021），FDG PET 代谢低下模式并不提示 AD（86% vs. 50%， p值 = 0.039）。我们的研究结果表明，高 tau PET 摄取与 Aβ 病理学和加速认知能力下降有关。在孤立性 Aβ(+) 的情况下，认知能力下降可能与多种发病情况（即混合型 AD）中 AD 谱系的变化有关。