Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239, USA.
Neurology. 2011 Aug 23;77(8):722-30. doi: 10.1212/WNL.0b013e31822b0068. Epub 2011 Aug 10.
To track cognitive change over time in dementia-free older adults and to examine terminal cognitive decline.
A total of 1,230 subjects who remained free from dementia over 14 years of follow-up were included in a population-based epidemiologic cohort study. First, we compared survivors and decedents on their trajectories of 5 cognitive functions (learning, memory, language, psychomotor speed, executive functions), dissociating practice effects which can mask clinically significant decline from age-associated cognitive decline. We used longitudinal mixed-effects models with penalized linear spline. Second, limiting the sample to 613 subjects who died during follow-up, we identified the inflection points at which the rate of cognitive decline accelerated, in relation to time of death, controlling for practice effects. We used mixed-effects model with a change point.
Age-associated cognitive trajectories were similar between decedents and survivors without dementia. However, substantial differences were observed between the trajectories of practice effects of survivors and decedents, resembling those usually observed between normal and mildly cognitively impaired elderly. Executive and language functions showed the earliest terminal declines, more than 9 years prior to death, independent of practice effects.
Terminal cognitive decline in older adults without dementia may reflect presymptomatic disease which does not cross the clinical threshold during life. Alternatively, cognitive decline attributed to normal aging may itself represent underlying neurodegenerative or vascular pathology. Although we cannot conclude definitively from this study, the separation of practice effects from age-associated decline could help identify preclinical dementia.
追踪无痴呆症的老年人群认知能力随时间的变化，并检查末期认知衰退。
共有 1230 名受试者在 14 年的随访期间保持无痴呆，他们被纳入一项基于人群的流行病学队列研究。首先，我们比较了幸存者和死亡者在 5 种认知功能（学习、记忆、语言、心理运动速度、执行功能）方面的轨迹，区分了可以掩盖与年龄相关的认知衰退的临床显著下降的练习效应。我们使用带有惩罚线性样条的纵向混合效应模型。其次，将样本限制在 613 名在随访期间死亡的受试者中，我们确定了认知衰退加速的拐点，这些拐点与死亡时间有关，同时控制了练习效应。我们使用带有变化点的混合效应模型。
无痴呆症的死亡者和幸存者的与年龄相关的认知轨迹相似。然而，幸存者和死亡者的练习效应轨迹之间存在显著差异，类似于正常和轻度认知障碍老年人之间通常观察到的差异。执行功能和语言功能显示出最早的末期下降，比死亡提前 9 年以上，与练习效应无关。
无痴呆症的老年人大脑的末期认知衰退可能反映了未达到临床阈值的疾病前期，或者归因于正常衰老的认知衰退本身可能代表潜在的神经退行性或血管病理。尽管我们不能从这项研究中得出明确的结论，但将练习效应与与年龄相关的衰退区分开来可能有助于识别临床前痴呆症。
