de Leon M J, Convit A, Wolf O T, Tarshish C Y, DeSanti S, Rusinek H, Tsui W, Kandil E, Scherer A J, Roche A, Imossi A, Thorn E, Bobinski M, Caraos C, Lesbre P, Schlyer D, Poirier J, Reisberg B, Fowler J
Center for Brain Health, New York University School of Medicine, New York, NY 10016, USA.
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10966-71. doi: 10.1073/pnas.191044198. Epub 2001 Aug 28.
Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.
神经病理学研究表明，轻度认知障碍（MCI）和阿尔茨海默病患者通常存在内嗅皮质（EC）、海马体（Hip）和颞叶新皮质的病变。体内成像的相关观察已能够从MCI预测痴呆症。尽管认知正常的个体可能存在局灶性EC病变，但尚未将该解剖结构作为认知衰退和脑变化的预测指标进行研究。这项磁共振成像（MRI）引导的2-[(18)F]氟-2-脱氧-d-葡萄糖/正电子发射断层扫描（FDG/PET）研究的目的是检验以下假设：在正常老年受试者中，EC代谢型谷氨酸（METglu）降低可预测衰退以及Hip和新皮质的受累情况。在一项对48名健康正常老年人进行的为期3年的纵向研究中，12名个体（平均年龄72岁）出现了认知衰退（11名发展为MCI，1名发展为阿尔茨海默病）。非衰退对照组在载脂蛋白E基因型、年龄、教育程度和性别方面进行了匹配。在基线时，EC的代谢降低准确预测了从正常到MCI的转变。在那些出现衰退的个体中，基线时的EC预测了纵向记忆和颞叶新皮质代谢降低。在随访时，出现衰退的个体在颞叶新皮质和Hip表现出记忆障碍和代谢减低。在那些出现衰退的受试者中，载脂蛋白E E4携带者的颞叶新皮质纵向代谢明显降低。总之，这些数据表明，在正常老年人中可以检测到脑受累的EC阶段，其可预测未来的认知和脑代谢降低。与E4相关的进行性代谢减低可能是已知的痴呆易感性增加的基础。需要进一步研究以评估个体风险，并确定在认知正常时检测到的METglu变化的生理基础。
