Apolipoprotein E ε4 and later-life decline in cognitive function and grip strength

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• The apolipoprotein E (APOE) ε4 allele is a known risk factor for dementia, while the ε2 allele is protective.
• Previous research suggests a link between APOE genotype and cognitive function changes.
• It remains unclear if observed cognitive differences are due to preclinical dementia in genetically susceptible individuals.

Purpose of the Study:

• To investigate the association between APOE genotype and initial cognitive performance and changes over time.
• To determine if APOE genotype effects on cognition persist after accounting for preclinical dementia.

Main Methods:

• A population-based Australian cohort of 590 participants aged 70+ was assessed up to four times over 12 years.
• Participants were genotyped for APOE.
• Cognitive outcomes included processing speed, verbal fluency, memory, and recognition tasks, alongside grip strength and reaction time.

Main Results:

• APOE ε4 carriers showed poorer initial memory and greater declines in processing speed and word recognition compared to ε2 and ε3 carriers.
• ε2 carriers had less decline in grip strength than ε3 carriers.
• These genotype effects on cognition became nonsignificant after excluding participants with low global cognition scores.

Conclusions:

• APOE ε4-associated cognitive decline in older adults may be attributed to a higher prevalence of preclinical dementia in ε4 carriers.
• When potential dementia cases are excluded, the link between APOE ε4 and cognitive decline is not statistically reliable.