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携带载脂蛋白E-IV基因阿尔茨海默病遗传风险者的记忆能力感知丧失与脑代谢衰退

Perceived loss of memory ability and cerebral metabolic decline in persons with the apolipoprotein E-IV genetic risk for Alzheimer disease.

作者信息

Ercoli Linda, Siddarth Prabha, Huang Sung-Cheng, Miller Karen, Bookheimer Susan Y, Wright Benjamin C, Phelps Michael E, Small Gary

机构信息

Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, 90024, USA.

出版信息

Arch Gen Psychiatry. 2006 Apr;63(4):442-8. doi: 10.1001/archpsyc.63.4.442.

Abstract

CONTEXT

Concerns about age-related memory loss are greater in persons who have the apolipoprotein E-IV (APOE4) genetic risk for Alzheimer disease, but the correlation between the degree of concerns and future cerebral metabolic decline is unknown.

OBJECTIVE

To investigate whether the degree of self-perceived memory loss is associated with regional cerebral metabolic decline.

DESIGN

Longitudinal study.

SETTING

Aging and Memory Research Center, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles.

PARTICIPANTS

Thirty right-handed, cognitively intact, middle-aged and older adults (age range, 50-82 years) with age-associated memory complaints, 14 of whom were carriers of the apolipoprotein E-IV allele, were recruited for longitudinal study.

MAIN OUTCOME MEASURES

At baseline, we administered a standardized neuropsychological battery and assessed self-appraisal of memory functioning using the Memory Functioning Questionnaire, which yields 4 factor scores indicating frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics use. Regional cerebral glucose metabolism was determined using fluorodeoxyglucose F18-positron emission tomography at baseline and after 2 years.

RESULTS

At baseline, APOE4 carriers and noncarriers did not differ significantly on objective memory measures or on Memory Functioning Questionnaire factor scores. However, the factor score for frequency of forgetting significantly correlated with global cerebral metabolic decline in all subjects regardless of APOE4 genetic risk (P = .01). By contrast, the factor score for mnemonics use significantly correlated with metabolic decline in the temporal regions in APOE4 carriers but not in noncarriers (P = .03).

CONCLUSIONS

The degree of perceived memory loss correlates with subsequent global cerebral metabolic decline for APOE4 carriers and noncarriers; hence, memory complaints may reflect underlying cerebral metabolic changes. Compensatory strategies, as reflected by more frequent mnemonics use in APOE4 carriers, may reflect underlying metabolic changes in the brain regions associated with prodromal Alzheimer disease. Self-reported mnemonics use may be helpful in identifying persons for clinical monitoring.

摘要

背景

对于有患阿尔茨海默病载脂蛋白E-IV(APOE4)遗传风险的人来说,对与年龄相关的记忆力减退的担忧更为强烈,但担忧程度与未来脑代谢衰退之间的相关性尚不清楚。

目的

研究自我感知的记忆力减退程度是否与局部脑代谢衰退相关。

设计

纵向研究。

地点

加利福尼亚大学洛杉矶分校塞梅尔神经科学与人类行为研究所衰老与记忆研究中心。

参与者

招募了30名右利手、认知功能完好的中老年人(年龄范围50 - 82岁),他们有与年龄相关的记忆问题,其中14人是载脂蛋白E-IV等位基因携带者,进行纵向研究。

主要观察指标

在基线时,我们实施了一套标准化神经心理测试,并使用记忆功能问卷评估记忆功能的自我评估,该问卷产生4个因子得分,分别表示遗忘频率(frequency of forgetting)、遗忘严重程度(seriousness of forgetting)、回顾性功能(retrospective functioning)和记忆术使用情况(mnemonics use)。在基线和2年后使用氟代脱氧葡萄糖F18正电子发射断层扫描确定局部脑葡萄糖代谢情况。

结果

在基线时,APOE4携带者和非携带者在客观记忆测试或记忆功能问卷因子得分上没有显著差异。然而,无论APOE4遗传风险如何,所有受试者中遗忘频率的因子得分与全脑代谢衰退显著相关(P = 0.01)。相比之下,记忆术使用的因子得分在APOE4携带者的颞叶区域与代谢衰退显著相关,而在非携带者中则不然(P = 0.03)。

结论

对于APOE4携带者和非携带者,感知到的记忆力减退程度与随后的全脑代谢衰退相关;因此,记忆问题可能反映了潜在的脑代谢变化。APOE4携带者更频繁地使用记忆术所反映的补偿策略,可能反映了与前驱性阿尔茨海默病相关脑区的潜在代谢变化。自我报告的记忆术使用情况可能有助于识别需要临床监测的人群。

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