Santangelo Roberto, Masserini Federico, Agosta Federica, Sala Arianna, Caminiti Silvia P, Cecchetti Giordano, Caso Francesca, Martinelli Vittorio, Pinto Patrizia, Passerini Gabriella, Perani Daniela, Magnani Giuseppe, Filippi Massimo
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):3152-3164. doi: 10.1007/s00259-020-04853-4. Epub 2020 May 15.
To know whether mild cognitive impairment (MCI) patients will develop Alzheimer's disease (AD) dementia in very short time or remain stable is of crucial importance, also considering new experimental drugs usually tested within very short time frames. Here we combined cerebrospinal fluid (CSF) AD biomarkers and a neurodegeneration marker such as brain FDG-PET to define an objective algorithm, suitable not only to reliably detect MCI converters to AD dementia but also to predict timing of conversion.
We included 77 consecutive MCI patients with neurological/neuropsychological assessment, brain 18F-FDG-PET and CSF analysis available at diagnosis and a neuropsychological/neurological evaluation every 6 months for a medium- to a long-term follow-up (at least 2 and up to 8 years). Binomial logistic regression models and Kaplan-Meier survival analyses were performed to determine the best biomarker (or combination of biomarkers) in detecting MCI converters to AD dementia and then, among the converters, those who converted in short time frames.
Thirty-five out of 77 MCI patients (45%) converted to AD dementia, with an average conversion time since MCI diagnosis of 26.07 months. CSF p-tau/Aβ42 was the most accurate predictor of conversion from MCI to AD dementia (82.9% sensitivity; 90% specificity). CSF p-tau/Aβ42 and FDG-PET-positive MCIs converted to AD dementia significantly earlier than the CSF-positive-only MCIs (median conversion time, 17.1 vs 31.3 months).
CSF p-tau/Aβ42 ratio and brain FDG-PET may predict both occurrence and timing of MCI conversion to full-blown AD dementia. MCI patients with both biomarkers suggestive for AD will likely develop an AD dementia shortly, thus representing the ideal target for any new experimental drug requiring short periods to be tested for.
了解轻度认知障碍（MCI）患者是否会在极短时间内发展为阿尔茨海默病（AD）痴呆或保持稳定至关重要，同时考虑到新的实验药物通常在非常短的时间内进行测试。在此，我们结合脑脊液（CSF）AD生物标志物和一种神经退行性变标志物，如脑FDG-PET，来定义一种客观算法，该算法不仅适用于可靠地检测向AD痴呆转化的MCI患者，还能预测转化时间。
我们纳入了77例连续的MCI患者，这些患者在诊断时进行了神经/神经心理学评估、脑18F-FDG-PET和CSF分析，并在中长期随访（至少2年至8年）期间每6个月进行一次神经心理学/神经学评估。进行二项逻辑回归模型和Kaplan-Meier生存分析，以确定检测向AD痴呆转化的MCI患者的最佳生物标志物（或生物标志物组合），然后在转化患者中确定那些在短时间内转化的患者。
77例MCI患者中有35例（45%）转化为AD痴呆，自MCI诊断以来的平均转化时间为26.07个月。CSF p-tau/Aβ42是从MCI转化为AD痴呆的最准确预测指标（敏感性82.9%；特异性90%）。CSF p-tau/Aβ42和FDG-PET阳性的MCI患者转化为AD痴呆的时间明显早于仅CSF阳性的MCI患者（中位转化时间分别为17.1个月和31.3个月）。
CSF p-tau/Aβ42比值和脑FDG-PET可预测MCI转化为全面AD痴呆的发生和时间。两种生物标志物均提示AD的MCI患者可能很快发展为AD痴呆，因此是任何需要短时间测试的新实验药物的理想靶点。
