School of Medicine, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle.
Veterans Affairs (VA) Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington.
JAMA Neurol. 2014 Jun;71(6):742-51. doi: 10.1001/jamaneurol.2014.445.
Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascular brain injury.
To use cerebrospinal fluid (CSF) biomarkers to gain insight into this complex trait.
DESIGN, SETTING, AND PARTICIPANTS: Secondary analyses of an academic multicenter cross-sectional (n = 315) and longitudinal (n = 158) study of 5 neuropsychological tests (Immediate Recall, Delayed Recall, Trail Making Test Parts A and B, and Category Fluency) in cognitively normal individuals aged 21 to 100 years.
To investigate the association of these cognitive function test results with age, sex, educational level, inheritance of the ε4 allele of the apolipoprotein E gene, and CSF concentrations of β-amyloid 42 (Aβ42) and tau (biomarkers of Alzheimer disease) as well as F2-isoprostanes (measures of free radical injury).
Age and educational level were broadly predictive of cross-sectional cognitive performance; of the genetic and CSF measures, only greater CSF F2-isoprostane concentration was significantly associated with poorer executive function (adjusted R2 ≤0.31). Longitudinal measures of cognitive abilities, except Category Fluency, also were associated broadly with age; of the genetic and CSF measures, only lower baseline CSF Aβ42 concentration was associated with longitudinal measures of immediate and delayed recall (marginal R2 ≤0.31).
Our results suggest that age and educational level accounted for a substantial minority of variance in cross-sectional or longitudinal cognitive test performance in this large group of cognitively normal adults. Latent Alzheimer disease and other diseases that produce free radical injury, such as vascular brain injury, accounted for a small amount of variation in cognitive test performance across the adult human life span. Additional genetic and environmental factors likely contribute substantially to age-related cognitive decline.
认知正常的老年人认知能力下降是一种复杂的特征，可能源于衰老过程、遗传脆弱性、环境因素以及共同潜在疾病的发展，这些疾病可进展为痴呆症，如阿尔茨海默病和血管性脑损伤。
利用脑脊液（CSF）生物标志物深入了解这一复杂特征。
设计、地点和参与者：对一项学术性多中心横断面（n = 315）和纵向（n = 158）研究的二次分析，该研究纳入了 5 项神经心理学测试（即时回忆、延迟回忆、连线测试 A 和 B、类别流畅性），共纳入认知正常的 21 至 100 岁个体。
研究这些认知功能测试结果与年龄、性别、教育程度、载脂蛋白 E 基因 ε4 等位基因遗传以及 CSF 中β-淀粉样蛋白 42（Aβ42）和 tau（阿尔茨海默病生物标志物）以及 F2-异前列腺素（自由基损伤的测量指标）浓度之间的关联。
年龄和教育程度广泛预测了横断面认知表现；在遗传和 CSF 测量指标中，只有 CSF F2-异前列腺素浓度更高与执行功能较差显著相关（调整 R2≤0.31）。除类别流畅性外，认知能力的纵向测量指标也广泛与年龄相关；在遗传和 CSF 测量指标中，只有较低的基线 CSF Aβ42 浓度与即时和延迟回忆的纵向测量指标相关（边缘 R2≤0.31）。
我们的结果表明，年龄和教育程度在认知正常的成年人中，解释了横断面或纵向认知测试表现的很大一部分差异。潜在的阿尔茨海默病和其他产生自由基损伤的疾病，如血管性脑损伤，在整个成年人生理范围内解释了认知测试表现的一小部分变化。其他遗传和环境因素可能对与年龄相关的认知能力下降有很大的影响。
