Caselli Richard J, Reiman Eric M, Locke Dona E C, Hutton Michael L, Hentz Joseph G, Hoffman-Snyder Charlene, Woodruff Bryan K, Alexander Gene E, Osborne David
Department of Neurology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA.
Arch Neurol. 2007 Sep;64(9):1306-11. doi: 10.1001/archneur.64.9.1306.
Memory declines more rapidly with age in apolipoprotein E (APOE) epsilon4 carriers than in APOE epsilon4 noncarriers, and APOE epsilon4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth.
To show that presymptomatic APOE epsilon4 homozygotes experience greater psychometric decline at a younger age than APOE epsilon4 heterozygotes and noncarriers before the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD).
Prospective observational study
Academic medical center.
A total of 43 APOE epsilon4 homozygotes, 59 APOE epsilon4 heterozygotes, and 112 APOE epsilon4 noncarriers aged 50 to 69 years were cognitively healthy and matched at entry according to age, educational level, and sex.
Neuropsychological battery given every 2 years.
Predefined test and cognitive domain decline criteria applied to consecutive epochs.
Of 214 participants, 48 showed no decline on any test, 126 showed decline on only 1 test in 1 or more domains, and 40 showed decline on 2 or more tests in 1 or more domains. Cognitive domain decline occurred in 4 of 10 APOE epsilon4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE epsilon4 heterozygotes and noncarriers (7.6%) (P = .02) and was more predictive of subsequent decline than nondomain decline (17 of 24 [70.8%] vs 29 of 70 [41.4%]; P = .01). Decline on any memory test was predictive of further decline (P < .001), as was memory domain decline (P = .006) in all genetic subgroups. Seven participants developed MCI (in 6) or AD (in 1), of whom 5 were APOE epsilon4 homozygotes (P = .008). Retrospective comparison showed that those who experienced multidomain, memory, and language domain decline had lower spatial and memory scores at entry than those who experienced no decline.
APOE epsilon4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE epsilon4 heterozygotes or noncarriers before the diagnosis of MCI and AD, thus confirming and characterizing the existence of a pre-MCI state in this genetic subset.
与载脂蛋白E（APOE）ε4非携带者相比，APOEε4携带者的记忆力随年龄下降得更快，且APOEε4纯合子的认知表现与应激源相关。尽管这些人年轻，但这些变化在某些情况下可能代表着症状前疾病。
证明在轻度认知障碍（MCI）和阿尔茨海默病（AD）诊断之前，症状前APOEε4纯合子在年轻时比APOEε4杂合子和非携带者经历更大的心理测量学衰退。
前瞻性观察性研究
学术医学中心。
共有43名APOEε4纯合子、59名APOEε4杂合子和112名APOEε4非携带者，年龄在50至69岁之间，认知健康，入组时根据年龄、教育水平和性别进行匹配。
每2年进行一次神经心理测试。
将预定义的测试和认知领域衰退标准应用于连续的时间段。
在214名参与者中，48名在任何测试中均未出现衰退，126名在1个或多个领域仅在1项测试中出现衰退，40名在1个或多个领域的2项或更多测试中出现衰退。入组时年龄在60岁及以上的10名APOEε4纯合子中有4名（40.0%）出现认知领域衰退，而66名APOEε4杂合子和非携带者中有5名（7.6%）出现衰退（P = 0.02），与非领域衰退相比，领域衰退更能预测随后的衰退（24名中的17名[70.8%]对70名中的29名[41.4%]；P = 0.01）。任何记忆测试中的衰退都可预测进一步衰退（P < 0.001），所有基因亚组中的记忆领域衰退也是如此（P = 0.006）。7名参与者发展为MCI（6名）或AD（1名），其中5名是APOEε4纯合子（P = 0.008）。回顾性比较显示，经历多领域、记忆和语言领域衰退的参与者入组时的空间和记忆得分低于未出现衰退的参与者。
在MCI和AD诊断之前，60多岁的APOEε4纯合子比APOEε4杂合子或非携带者的认知领域衰退率更高，从而证实并描述了该基因亚组中存在MCI前状态。
