Executive function changes before memory in preclinical Alzheimer's pathology: a prospective, cross-sectional, case control study.
Executive function changes before memory in preclinical Alzheimer's pathology: a prospective, cross-sectional, case control study.
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DOI：
10.1371/journal.pone.0079378
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fonteh AN
中科院分区：
文献类型：
--
作者：
Harrington MG;Chiang J;Pogoda JM;Gomez M;Thomas K;Marion SD;Miller KJ;Siddarth P;Yi X;Zhou F;Lee S;Arakaki X;Cowan RP;Tran T;Charleswell C;Ross BD;Fonteh AN
早期治疗阿尔茨海默病可能会减少其破坏性影响。通过集中研究阿尔茨海默病病理学（临床前阶段）的无症状个体，可以发现疾病的早期指标。脑脊液β-淀粉样蛋白42减少是临床前疾病的第一个指标，但尚不清楚哪种病理导致第一个临床效应。我们的假设是，正常范围内的神经心理学变化将有助于预测临床前疾病和定位早期病理。我们招募了可能患有阿尔茨海默病的成年人或无症状的认知健康成年人，在医学和神经心理学检查后进行分类。通过逻辑回归，我们得出了脑脊液β淀粉样蛋白42/tau比值的截止值，该比值正确分类了85%的阿尔茨海默病患者。我们将无症状组分为有（n = 34;临床前阿尔茨海默病）和无（n = 36;对照组）β淀粉样蛋白42/tau比值异常;这些亚组在年龄、性别、教育、药物、载脂蛋白-ε基因型、血管危险因素和小血管疾病的磁共振成像特征方面具有相似的分布。神经心理学数据的多变量分析显示，只有Stroop干扰（反应抑制）独立预测临床前病理（OR = 0.13，95%CI = 0.04-0.42）。 缺乏纵向和尸检数据，年龄较大，人口规模小是本研究的局限性。我们的数据表明，早期淀粉样蛋白病理生理学的临床效应先于海马神经元内病理学的临床效应。在记忆受损之前，脑脊液β淀粉样蛋白42改变并伴有执行能力下降，这与首先出现在基底同皮质中的细胞外淀粉样蛋白沉积相匹配，随后才涉及海马。我们建议，Stroop干扰可能是一个额外的重要屏幕的早期病理和有用的监测治疗临床前阿尔茨海默氏病;措施的执行和记忆功能的纵向设计将是必要的，以更充分地评估这种方法。
Early treatment of Alzheimer’s disease may reduce its devastating effects. By focusing research on asymptomatic individuals with Alzheimer’s disease pathology (the preclinical stage), earlier indicators of disease may be discovered. Decreasing cerebrospinal fluid beta-amyloid42 is the first indicator of preclinical disorder, but it is not known which pathology causes the first clinical effects. Our hypothesis is that neuropsychological changes within the normal range will help to predict preclinical disease and locate early pathology. We recruited adults with probable Alzheimer’s disease or asymptomatic cognitively healthy adults, classified after medical and neuropsychological examination. By logistic regression, we derived a cutoff for the cerebrospinal fluid beta amyloid42/tau ratios that correctly classified 85% of those with Alzheimer’s disease. We separated the asymptomatic group into those with (n = 34; preclinical Alzheimer’s disease) and without (n = 36; controls) abnormal beta amyloid42/tau ratios; these subgroups had similar distributions of age, gender, education, medications, apolipoprotein-ε genotype, vascular risk factors, and magnetic resonance imaging features of small vessel disease. Multivariable analysis of neuropsychological data revealed that only Stroop Interference (response inhibition) independently predicted preclinical pathology (OR = 0.13, 95% CI = 0.04–0.42). Lack of longitudinal and post-mortem data, older age, and small population size are limitations of this study. Our data suggest that clinical effects from early amyloid pathophysiology precede those from hippocampal intraneuronal neurofibrillary pathology. Altered cerebrospinal fluid beta amyloid42 with decreased executive performance before memory impairment matches the deposits of extracellular amyloid that appear in the basal isocortex first, and only later involve the hippocampus. We propose that Stroop Interference may be an additional important screen for early pathology and useful to monitor treatment of preclinical Alzheimer’s disease; measures of executive and memory functions in a longitudinal design will be necessary to more fully evaluate this approach.
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DOI：
10.1017/s1355617705050782
发表时间：
2005-10-01
影响因子：
2.6
作者：
Benedict, RHB
通讯作者：
Benedict, RHB
影响因子：
3.7
作者：
Balota, David A.;Tse, Chi-Shing;Hutchison, Keith A.;Spieler, Daniel H.;Duchek, Janet M.;Morris, John C.
通讯作者：
Morris, John C.
影响因子：
11.1
作者：
Fagan, Anne M.;Mintun, Mark A.;Shah, Aarti R.;Aldea, Patricia;Roe, Catherine M.;Mach, Robert H.;Marcus, Daniel;Morris, John C.;Holtzman, David M.
通讯作者：
Holtzman, David M.
影响因子：
9.9
作者：
Godbolt, AK;Waldman, AD;Rossor, MN
通讯作者：
Rossor, MN
影响因子：
4
作者：
Chien, David T.;Bahri, Shadfar;Kolb, Hartmuth C.
通讯作者：
Kolb, Hartmuth C.