Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease
Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease
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DOI：
10.1212/wnl.53.7.1391
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发表时间：
1999-10-22
期刊：
影响因子：
9.9
通讯作者：
Avison, MJ
中科院分区：
文献类型：
--
作者：
Smith, CD;Andersen, AH;Avison, MJ
目的：确定认知正常的 AD 高危个体的脑功能是否在该疾病的典型发病年龄之前几年发生改变。背景：AD 的神经病理学改变先于认知障碍数年。目前尚不清楚神经回路的功能改变是否伴随这些神经病理学变化，如果是的话，它们是否可以在症状出现之前被检测到。方法：我们使用功能性 MRI 来比较两组认知正常女性的皮质激活情况，仅她们患 AD 的风险不同。视觉命名和字母流畅性任务被用来激活有助于物体和面部识别的大脑区域，这些区域是先前描述的 AD 中代谢低下和神经病理改变的部位。风险群体的 AD 家族史和载脂蛋白 E 等位基因状态不同，但年龄、教育程度和认知表现指标相匹配。研究参与者的平均年龄为 52 岁。结果：各组之间大脑激活的区域模式相似。然而，尽管命名和字母流利度表现相同，但高风险组在这两项任务中，双侧中颞下区和后颞下区的激活区域显着减少。结论：患有 AD 高风险的认知正常个体表现出在命名和流利性任务中参与的关键区域的大脑激活减少。高风险组的激活减少可能是颞下区或该区域输入中存在亚临床神经病理学的结果。如果是这样，这些发现提供了在有症状的 AD 出现之前进行疾病缓解治疗的机会窗口的证据。
Objective: To determine whether brain function is altered in cognitively normal individuals at high risk for AD several years before the typical age at onset for this illness. Background: Neuropathologic alterations in AD precede cognitive impairment by several years. It is unknown whether functional alterations in neural circuitry accompany these neuropathologic changes, and if so, whether they may be detectable before onset of symptoms. Methods: We used functional MRI to compare cortical activation between two groups of cognitively normal women differing only in their risk for developing AD. Visual naming and letter fluency tasks were used to activate brain areas subserving object and face recognition, previously described sites of hypometabolism and neuropathologic alteration in AD. The risk groups differed in family history of AD and apolipoprotein E allele status, but were matched in age, education, and measures of cognitive performance. Average age of the study participants was 52 years. Results: The regional patterns of brain activation were similar between groups. However, the high risk group showed areas of significantly reduced activation in the mid- and posterior inferotemporal regions bilaterally during both tasks despite identical naming and letter fluency performance. Conclusions: Cognitively normal individuals at high risk for AD demonstrate decreased brain activation in key areas engaged during naming and fluency tasks. Decreased activation in the high risk group may be a consequence of the presence of subclinical neuropathology in the inferotemporal region or in the inputs to that region. If so, these findings provide evidence of a window of opportunity for disease-modifying treatment before the onset of symptomatic AD.