Apolipoprotein E ε4 and Later-Life Decline in Cognitive Function and Grip Strength

Objectives: Presence of the apolipoprotein E (APOE) epsilon 4 allele is a risk factor for dementia, whereas the epsilon 2 allele offers protection against dementia. There is also evidence for a relationship between APOE genotype and changes in cognitive function. It is not clear, however, whether this relationship stems from undetected disease in persons genetically more vulnerable to dementia. This study examined whether APOE genotype was associated with either initial performance or change in performance on a range of cognitive and noncognitive tasks, after accounting for possible preclinical dementia. Design: A population-based cohort was assessed up to four times over 12 years. Participants: The sample was an Australian cohort of 590 participants age 70 years and older who were genotyped for APOE. Measurements: The outcomes were processing speed, verbal fluency, episodic memory, word recognition, face recognition, grip strength, and reaction time. Results: Adjusted latent growth models indicated that epsilon 4 carriers had significantly poorer initial memory performance and greater declines in processing speed and word recognition than epsilon 2 and epsilon 3 carriers. In addition, epsilon 2 carriers exhibited significantly less decline in right grip strength than epsilon 3 carriers. However, after excluding 125 participants with low global cognition scores, all genotype effects became nonsignificant. Conclusions: Over a 12-year period, findings indicate that APOE epsilon 4-related cognitive decline in older community-dwelling populations is due to a higher likelihood of preclinical dementia among epsilon 4 carriers. When possible dementia cases are removed from the analyses, epsilon 4 associations with cognitive decline become statistically unreliable.