From the Department of Psychiatry (A.J.J.), Center for Behavior Genetics of Aging (D.E.G., J.A.E., M.S.P., C.E.F., J.Z., M.S.-C., W.S.K.), University of California, San Diego, La Jolla; Department of Medicine (D.E.G.), Vanderbilt University Medical Center, Nashville, TN; Department of Psychology (M.S.-C.), San Diego State University; Department of Psychology (C.A.R.), University of California; Department of Psychiatry and Behavioral Neuroscience (K.C.J.), University of Chicago, IL; Department of Epidemiology and Biostatistics (H.X.), St. Louis University; Clinical Epidemiology Center (H.X.), Veterans Affairs St. Louis Healthcare System, MO; Psychology Service (A.J.J.) and Center of Excellence for Stress and Mental Health (A.J.J., W.S.K.), Veterans Affairs San Diego Healthcare System, CA; and Department of Psychological and Brain Sciences (R.T., M.J.L.), Boston University, MA.
Neurology. 2020 Aug 25;95(8):e973-e983. doi: 10.1212/WNL.0000000000010130. Epub 2020 Jun 30.
To test the hypothesis that individual differences in episodic memory and verbal fluency in cognitively normal middle-aged adults will predict progression to amnestic mild cognitive impairment (MCI) after 6 years.
The cohort analyzed included 842 male twins who were cognitively normal at baseline (mean 56 years) and completed measures of episodic memory and verbal fluency at baseline and again 6 years later (mean 62 years).
Poor episodic memory predicted progression to both amnestic MCI (odds ratio [OR], 4.42; 95% confidence interval [CI], 2.44-10.60) and nonamnestic MCI (OR, 1.92; 95% CI, 1.32-3.44). Poor semantic verbal fluency also independently predicted progression to amnestic MCI (OR, 1.86; 95% CI, 1.12-3.52). In the full sample, a semantic-specific fluency latent variable at wave 1 (which controls for letter fluency) predicted change in episodic memory at wave 2 (β = 0.13), but not vice versa (β = 0.04). Associations between episodic memory and verbal fluency factors were primarily explained by genetic, rather than environmental, correlations.
Among individuals who were cognitively normal at wave 1, episodic memory moderately to strongly predicted progression to MCI at average age 62, emphasizing the fact that there is still meaningful variability even among cognitively normal individuals. Episodic memory, which is typically a primary focus for Alzheimer disease (AD) risk, declined earlier and more quickly than fluency. However, semantic fluency at average age 56 predicted 6-year change in memory as well as progression to amnestic MCI even after accounting for baseline memory performance. These findings emphasize the utility of memory and fluency measures in early identification of AD risk.
验证以下假设，即认知正常的中年个体在情景记忆和词语流畅性方面的个体差异将预测其在 6 年后进展为遗忘型轻度认知障碍（MCI）。
分析的队列包括 842 名男性双胞胎，他们在基线时认知正常（平均年龄 56 岁），并在基线和 6 年后（平均年龄 62 岁）完成情景记忆和词语流畅性测量。
较差的情景记忆预测会进展为遗忘型 MCI（优势比 [OR]，4.42；95%置信区间 [CI]，2.44-10.60）和非遗忘型 MCI（OR，1.92；95% CI，1.32-3.44）。较差的语义词语流畅性也独立地预测会进展为遗忘型 MCI（OR，1.86；95% CI，1.12-3.52）。在全样本中，第 1 波的语义特异性流畅性潜在变量（控制字母流畅性）预测第 2 波的情景记忆变化（β=0.13），反之则不然（β=0.04）。情景记忆和词语流畅性因素之间的关联主要由遗传解释，而非环境解释。
在第 1 波认知正常的个体中，情景记忆中度至强烈地预测了在平均年龄 62 岁时进展为 MCI，这强调了即使在认知正常的个体中，仍然存在有意义的变异性。情景记忆通常是阿尔茨海默病（AD）风险的主要关注点，它比流畅性更早且更快地下降。然而，即使在考虑到基线记忆表现后，56 岁时的语义流畅性也预测了 6 年的记忆变化以及遗忘型 MCI 的进展。这些发现强调了记忆和流畅性测量在 AD 风险早期识别中的效用。
