The influence of APOE status on rate of cognitive decline

Geroscience. 2024 Jun;46(3):3263-3274. doi: 10.1007/s11357-024-01069-4. Epub 2024 Jan 22.


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.

Keywords: APOE status; Cognitive change; Cognitively unimpaired older adults; Mild cognitive impairment; Subjective cognitive decline.

MeSH terms

  • Aged
  • Alzheimer Disease* / complications
  • Apolipoprotein E4 / genetics
  • Cognitive Dysfunction* / genetics
  • Genotype
  • Humans


  • Apolipoprotein E4