Royall Donald R, Palmer Raymond F
Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, USA.
Department of Medicine, The University of Texas Health Science Center, San Antonio, TX, USA.
Oncotarget. 2016 Mar 22;7(12):13307-18. doi: 10.18632/oncotarget.7759.
Structural Equation Models (SEM) can explicitly distinguish "dementia-relevant" variance in cognitive task performance (i.e., "δ" for dementia). In prior work, δ appears to uniquely account for dementia severity regardless of the cognitive measures used to construct it. In this study, we test δ as a mediator of age's prospective association with future cognitive performance and dementia severity in a large, ethnically diverse longitudinal cohort, the Texas Alzheimer's Research and Care Consortium (TARCC). Age had adverse effects on future cognition, and these were largely mediated through δ, independently of education, ethnicity, gender, depression ratings, serum homo-cysteine levels, hemoglobin A1c, and apolipoprotein e4 status. Age explained 4% of variance in δ, and through it, 11-18% of variance in future cognitive performance. Our findings suggest that normative aging is a dementing condition (i.e., a "senility"). While the majority of variance in dementia severity must be independent of age, age's specific effect is likely to accumulate over the lifespan. Our findings also constrain age's dementing effects on cognition to the age-related fraction of "general intelligence" (Spearman's "g"). That has broad biological and pathophysiological implications.
结构方程模型（SEM）能够明确区分认知任务表现中“与痴呆相关的”方差（即痴呆的“δ”）。在先前的研究中，无论用于构建它的认知测量方法如何，δ似乎都能唯一地解释痴呆的严重程度。在本研究中，我们在一个大型、种族多样的纵向队列——德克萨斯州阿尔茨海默病研究与护理联盟（TARCC）中，测试δ作为年龄与未来认知表现及痴呆严重程度前瞻性关联的中介变量。年龄对未来认知有不利影响，且这些影响很大程度上是通过δ介导的，与教育程度、种族、性别、抑郁评分、血清同型半胱氨酸水平、糖化血红蛋白和载脂蛋白e4状态无关。年龄解释了δ中方差的4%，并通过它解释了未来认知表现中方差的11 - 18%。我们的研究结果表明，正常衰老就是一种痴呆状态（即“衰老”）。虽然痴呆严重程度的大部分方差必定与年龄无关，但年龄的特定影响可能会在整个生命周期中累积。我们的研究结果还将年龄对认知的痴呆影响限制在“一般智力”（斯皮尔曼的“g”）中与年龄相关的部分。这具有广泛的生物学和病理生理学意义。
