Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands.
Psychol Med. 2009 Nov;39(11):1907-11. doi: 10.1017/S0033291709005492. Epub 2009 Apr 1.
We aimed to compare the rate of cognitive decline in patients with early and late onset Alzheimer's disease (AD) and to investigate the potentially modifying influence of the apolipoprotein E (APOE) genotype.
We included 99 patients with early onset AD (age 65 years) and 192 patients with late onset AD (age >65 years) who had at least two scores on the Mini-Mental State Examination (MMSE) (range 2-14) obtained at least 1 year apart. Linear mixed models were performed to investigate the rate of cognitive decline dependent on age at onset (AAO) and APOE genotype.
The mean (S.D.) age for patients with early onset AD was 57.7 (4.5) years, and 74.5 (5.1) years for patients with late onset AD. AAO was not associated with baseline MMSE [beta (S.E.)=0.8 (0.5), p=0.14]. However, patients with early onset showed a faster decline on the MMSE [beta (S.E.)=2.4 (0.1) points/year] than those with late onset [beta (S.E.)=1.7 (0.1) points/year, p=0.00]. After stratification according to APOE genotype, APOE epsilon4 non-carriers with early onset showed faster cognitive decline than non-carriers with late onset [2.4 (0.3) v. 1.3 (0.3) points/year, p=0.01]. In APOE epsilon4 carriers, no difference in rate of cognitive decline was found between patients with early and late onset [beta (S.E.)=0.2 (0.2), p=0.47].
Patients with early onset AD show more rapid cognitive decline than patients with late onset, suggesting that early onset AD follows a more aggressive course. Furthermore, this effect seems to be most prominent in patients with early onset who do not carry the genetic APOE epsilon4 risk factor for AD.
我们旨在比较早发性和晚发性阿尔茨海默病（AD）患者的认知能力下降率，并研究载脂蛋白 E（APOE）基因型的潜在修饰作用。
我们纳入了 99 例早发性 AD 患者（年龄 65 岁）和 192 例晚发性 AD 患者（年龄＞65 岁），这些患者的 Mini-Mental State Examination（MMSE）评分至少有两次，两次评分的时间间隔至少为 1 年。采用线性混合模型来研究认知能力下降率与发病年龄（AAO）和 APOE 基因型的关系。
早发性 AD 患者的平均（SD）年龄为 57.7（4.5）岁，晚发性 AD 患者的平均年龄为 74.5（5.1）岁。AAO 与 MMSE 的基线评分无关[β（SE）=0.8（0.5），p=0.14]。然而，早发性 AD 患者的 MMSE 评分下降速度较快[β（SE）=2.4（0.1）分/年]，而晚发性 AD 患者的 MMSE 评分下降速度较慢[β（SE）=1.7（0.1）分/年，p=0.00]。根据 APOE 基因型进行分层后，早发性非 APOE epsilon4 携带者的认知能力下降速度快于晚发性非携带者[2.4（0.3）v. 1.3（0.3）分/年，p=0.01]。在 APOE epsilon4 携带者中，早发性和晚发性 AD 患者的认知能力下降率无差异[β（SE）=0.2（0.2），p=0.47]。
早发性 AD 患者的认知能力下降速度快于晚发性 AD 患者，提示早发性 AD 具有更具侵袭性的病程。此外，在不携带 AD 的 APOE epsilon4 遗传风险因素的早发性 AD 患者中，这种影响似乎最为明显。
