Analyses based on 3 longitudinal clinical-pathologic cohort studies in the US concluded that awareness of memory impairment typically begins to decline about 2–3 years before dementia onset and is associated with postmortem evidence of transactive response DNA-binding protein 43 (TDP-43) pathology, tau tangles, and gross cerebral infarcts. The analyses included 2,092 persons>50-years-old who had no memory or cognitive impairment at baseline. In the full group, memory ratings were modestly correlated with memory performance. Each person’s memory performance was regressed on their memory ratings, and the residuals provided longitudinal indicators of memory awareness. In a subset of 239 persons who developed dementia, episodic memory awareness was stable until a mean of 2.6 years before dementia onset; thereafter, memory awareness declined rapidly. Older age at baseline was associated with later onset of memory unawareness. In a subset of 385 persons who died and underwent neuropathologic examination, TDP-43 pathology, tau tangles, and gross cerebral infarcts were related to decline in memory awareness. In the absence of these pathologies, no decline in memory awareness was evident. Results were similar in subgroups with and without dementia. The data suggest that unawareness of amnestic dysfunction is part of the natural history of late-life dementia and is driven by accumulation of dementia-related pathologies. Source: http://www.neurology.org/
根据美国3个纵向临床病理群组研究分析得出的结论是，记忆障碍的认知通常在痴呆症发病前约2 – 3年开始下降，并与尸检证实的中介反应DNA结合蛋白43（TDP-43）病理，tau蛋白缠结和脑梗塞总值相关。该分析包括起初没有记忆或认知障碍的2092人， 50岁以上。整组的记忆评级与记忆功能小幅相关。对每人的记忆功能和记忆评级进行回归，其残差即为记忆意识的纵向指标。在发生痴呆症的239人的一个亞组，情节记忆的认知直到平均痴呆症发病前2.6年是稳定的；此后，记忆意识迅速下降。起初年龄较大者与后来发生的不觉失忆有关。在385人的一个亞组死后接受了神经病理学检查，TDP-43病理，tau蛋白缠结和脑梗塞总值均与记忆意识下降有关。如果没有这些病理表现，则无明显记忆意识下降趋势。无论有无痴呆，结果类似。该资料提示，无意识遗忘功能障碍是晚年痴呆的自然病程的一部分，是痴呆相关病理积累所致。来源：http://www.neurology.org/