Tort-Merino Adrià, Valech Natalia, Peñaloza Claudia, Grönholm-Nyman Petra, León María, Olives Jaume, Estanga Ainara, Ecay-Torres Mirian, Fortea Juan, Martínez-Lage Pablo, Molinuevo José L, Laine Matti, Rodríguez-Fornells Antoni, Rami Lorena
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic, Barcelona, Spain.
Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute- IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
J Alzheimers Dis. 2017;58(3):855-870. doi: 10.3233/JAD-161173.
We employed a highly demanding experimental associative learning test (the AFE-T) to explore memory functioning in Preclinical Alzheimer's Disease stage 1 (PreAD-1) and stage 2 (PreAD-2). The task consisted in the learning of unknown object/name pairs and our comprehensive setup allowed the analysis of learning curves, immediate recall, long-term forgetting rates at one week, three months, and six months, and relearning curves. Forty-nine cognitively healthy subjects were included and classified according to the presence or absence of abnormal CSF biomarkers (Control, n = 31; PreAD-1, n = 14; PreAD-2, n = 4). Control and PreAD-1 performances on the experimental test were compared by controlling for age and education. These analyses showed clear learning difficulties in PreAD-1 subjects (F = 6.98; p = 0.01). Between-group differences in long-term forgetting rates were less notable, reaching statistical significance only for the three-month cued forgetting rate (F = 4.83; p = 0.03). Similarly, relearning sessions showed only statistical trends between the groups (F = 3.22; p = 0.08). In the whole sample, significant correlations between CSF Aβ42/tau ratio and the AFE-T were found, both in the total learning score (r = 0.52; p < 0.001) and in the three-month cued forgetting rate (r = -0.38; p < 0.01). Descriptive subanalyses involving PreAD-2 suggested greater learning and recall difficulties in these subjects when compared with the PreAD-1 group. The present results suggest that explicit learning difficulties when binding information could be one of the earliest signs of the future emergence of episodic memory difficulties on the Alzheimer's disease continuum. Our findings indicate that the AFE-T is a sensitive test, capable of detecting subtle memory difficulties in PreAD-1.
我们采用了一项要求极高的实验性联想学习测试（AFE-T）来探究临床前阿尔茨海默病1期（PreAD-1）和2期（PreAD-2）的记忆功能。该任务包括学习未知的物体/名称对，我们全面的设置允许分析学习曲线、即时回忆、一周、三个月和六个月时的长期遗忘率以及重新学习曲线。纳入了49名认知健康的受试者，并根据脑脊液生物标志物是否异常进行分类（对照组，n = 31；PreAD-1组，n = 14；PreAD-2组，n = 4）。通过控制年龄和教育程度，比较了对照组和PreAD-1组在实验测试中的表现。这些分析表明PreAD-1组受试者存在明显的学习困难（F = 6.98；p = 0.01）。组间长期遗忘率的差异不太显著，仅在三个月的线索遗忘率方面达到统计学意义（F = 4.83；p = 0.03）。同样，重新学习环节在组间仅显示出统计学趋势（F = 3.22；p = 0.08）。在整个样本中，发现脑脊液Aβ42/tau比值与AFE-T之间存在显著相关性，无论是在总学习分数方面（r = 0.52；p < 0.001）还是在三个月的线索遗忘率方面（r = -0.38；p < 0.01）。涉及PreAD-2组的描述性亚分析表明，与PreAD-1组相比，这些受试者存在更大的学习和回忆困难。目前的结果表明，在绑定信息时出现的显性学习困难可能是阿尔茨海默病连续体上未来出现情景记忆困难的最早迹象之一。我们的研究结果表明，AFE-T是一种敏感的测试，能够检测出PreAD-1中的细微记忆困难。
