Accelerated long-term forgetting (ALF) is the phenomenon whereby material is retained normally over short intervals (e.g. minutes) but forgotten abnormally rapidly over longer periods (days or weeks). ALF may be an early marker of cognitive decline, but little is known about its relationships with preclinical Alzheimer’s disease pathology, and how memory selectivity may influence which material is forgotten. We assessed ALF in ‘Insight 46’, a sub-study of the MRC National Survey of Health and Development (a population-based cohort born during one week in 1946) (n=429; 47% female; assessed aged ∼73 years). ALF assessment comprised visual and verbal memory tests: Complex Figure Drawing and the Face-Name Associative Memory Exam (FNAME). ALF scores were calculated as the percentage of material retained after 7 days, relative to 30 minutes. In 306 cognitively-normal participants, we investigated effects on ALF of β-amyloid pathology (quantified using 18F-Florbetapir-PET, classified as positive/negative) and whole-brain and hippocampal atrophy rate (quantified from serial T1-MRI over ∼2.4 years preceding the ALF assessment), as well as interactions between these pathologies. We categorized Complex Figure Drawing items as ‘outline’ or ‘detail’, to test our hypothesis that forgetting the outline of the structure would be more sensitive to the effect of brain pathologies. We also investigated associations between ALF and Subjective Cognitive Decline, measured with the MyCog questionnaire. Complex Figure ‘outline’ items were better retained than ‘detail’ items (mean retention over 7 days = 94% vs 72%). Amyloid-positive participants showed greater forgetting of the Complex Figure outline, compared to amyloid-negatives (90% vs 95%; P<0.01). There were interactions between amyloid pathology and cerebral atrophy, such that whole-brain and hippocampal atrophy predicted greater ALF on Complex Figure Drawing among amyloid-positives only (e.g. 1.9 percentage-points lower retention per ml/year of whole-brain atrophy [95% confidence intervals 0.5, 3.7]; P<0.05). Greater ALF on FNAME was associated with increased rate of hippocampal atrophy. ALF on Complex Figure Drawing also correlated with subjective cognitive decline (-0.45 percentage-points per MyCog point [-0.85, -0.05], P<0.05). These results provide evidence of associations between some measures of ALF and biomarkers of brain pathologies and subjective cognitive decline in cognitively-normal older adults. On Complex Figure Drawing, ‘outline’ items were better remembered than ‘detail’ items – illustrating the strategic role of memory selectivity – but ‘outline’ items were also relatively more vulnerable to ALF in individuals with amyloid pathology. Overall, our findings suggest that ALF may be a sensitive marker of cognitive changes in preclinical Alzheimer’s disease.

中文翻译：

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老年人加速遗忘、淀粉样蛋白沉积和脑萎缩之间的关联


加速长期遗忘 （ALF） 是指材料在短时间内（例如几分钟）正常保留，但在较长时间（几天或几周）内异常迅速地遗忘的现象。ALF 可能是认知能力下降的早期标志，但对其与临床前阿尔茨海默病病理的关系以及记忆选择性如何影响被遗忘的材料知之甚少。我们在 MRC 全国健康与发展调查的子研究“Insight 46”中评估了 ALF（1946 年一周内出生的基于人群的队列）（n=429;47% 为女性;评估年龄约为 73 岁）。ALF 评估包括视觉和语言记忆测试：复杂图形绘图和人脸名称联想记忆检查 （FNAME）。ALF 评分计算为 7 天后相对于 30 分钟的材料保留百分比。在 306 名认知正常的参与者中，我们调查了 β-淀粉样蛋白病理学（使用 18F-Florbetapir-PET 量化，分类为阳性/阴性）和全脑和海马萎缩率（根据 ALF 评估前 2.4 年内的连续 T1-MRI 量化）对 ALF 的影响，以及这些病理之间的相互作用。我们将复杂人物绘画项目分类为 “轮廓 ”或 “细节”，以检验我们的假设，即忘记结构的轮廓对大脑病变的影响更敏感。我们还调查了 ALF 与主观认知能力下降之间的关联，使用 MyCog 问卷测量。复杂图表的“大纲”项目比“细节”项目的保留率更高（7 天的平均保留率 = 94% 对 72%）。与淀粉样蛋白阴性者相比，淀粉样蛋白阳性参与者表现出对复杂图大纲的遗忘更多（90% 对 95%;P<0.01）。 淀粉样蛋白病理学与脑萎缩之间存在相互作用，因此，全脑和海马萎缩仅在淀粉样蛋白阳性者中预测复杂图形绘制的 ALF 更高（例如，全脑萎缩每毫升/年的保留率降低 1.9 个百分点 [95% 置信区间 0.5、3.7];P<0.05）。FNAME 上较高的 ALF 与海马萎缩率增加相关。复杂图形绘图的 ALF 也与主观认知能力下降相关 （每 MyCog 点 -0.45 个百分点 [-0.85， -0.05]，P<0.05）。这些结果提供了 ALF 的某些测量与认知正常老年人脑病理和主观认知能力下降的生物标志物之间存在关联的证据。在复杂图形绘图中，“大纲”项目比“细节”项目更容易记住——这说明了记忆选择性的战略作用——但在淀粉样蛋白病理学个体中，“大纲”项目也相对更容易受到 ALF 的影响。总体而言，我们的研究结果表明 ALF 可能是临床前阿尔茨海默病认知变化的敏感标志物。