Abstract

Background

Apolipoprotein (APOE) ɛ4 positivity and subjective cognitive decline (SCD) both increase risk of Alzheimer’s disease (AD) development. However, few studies have examined the relationship between SCD and APOE status, especially using longitudinal data. The current study examined whether APOE is associated with the rate of cognitive change in SCD and mild cognitive impairment (MCI).

Methods

A sample of 3494 older adults (1990 normal controls, NC, 775 SCD, and 729 MCI) with a mean follow-up of 9.09 years were included from the Rush Alzheimer’s Disease Center Research Sharing Hub. Linear mixed effects models examined the relationship between APOE status and cognitive change in older adults with SCD normal controls, and people with MCI.

Results

The presence of at least one ɛ2 allele in SCD and MCI results in cognitive change rates similar to a NC with the ɛ3ɛ3 genotype. Older adult SCD-ɛ4 individuals exhibited increased rate of cognitive decline compared to all groups, including NC-ɛ4 and MCI-ɛ4.

Conclusion

People with SCD with at least one ɛ4 allele experience increased rates of cognitive decline compared to cognitively healthy older adults and people with MCI. These findings have important implications for treatments and interventions and can improve future research and clinical trials by targeting people in the preclinical AD phase (i.e., SCD) who also possess at least one APOE ɛ4 allele.

中文翻译：

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APOE 状态对认知衰退率的影响

摘要

背景

载脂蛋白 (APOE) ɛ4 阳性和主观认知能力下降 (SCD) 都会增加患阿尔茨海默病 (AD) 的风险。然而，很少有研究探讨 SCD 和 APOE 状态之间的关系，特别是使用纵向数据。当前的研究检验了 APOE 是否与 SCD 和轻度认知障碍 (MCI) 的认知变化率相关。

方法

Rush 阿尔茨海默病中心研究共享中心纳入了 3494 名老年人样本（1990 名正常对照、NC、775 名 SCD 和 729 名 MCI），平均随访时间为 9.09 年。线性混合效应模型研究了患有 SCD 正常对照的老年人和患有 MCI 的人的 APOE 状态与认知变化之间的关系。

结果

SCD 和 MCI 中至少存在一个 ɛ2 等位基因会导致认知变化率与具有 ɛ3ɛ3 基因型的 NC 相似。与所有群体（包括 NC-ɛ4 和 MCI-ɛ4）相比，老年人 SCD-ɛ4 个体的认知能力下降速度更快。

结论

与认知健康的老年人和 MCI 患者相比，携带至少一种 ɛ4 等位基因的 SCD 患者的认知能力下降率更高。这些发现对治疗和干预具有重要意义，并且可以通过针对同时拥有至少一种 APOE ɛ4 等位基因的临床前 AD 阶段（即 SCD）人群来改善未来的研究和临床试验。