Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study comparing genetic subgroups over 2 years
PubMed 11756601 · doi:10.1212/wnl.57.12.2223
What was done
A prospective cohort of 25 healthy women in their sixth decade—16 APOE-epsilon4 carriers (mean age 55.1 ± 6.0 years) and 9 non-carriers (mean age 60.6 ± 10.2 years)—underwent high-resolution 1.5-Tesla MRI and neurocognitive testing at baseline and after 2 years. Hippocampal volume was manually outlined across sagittal slices. The cognitive battery included the Buschke-Fuld Free Recall, verbal fluency tests, Rey Figure Test, Wechsler Memory Scale-Revised, and WAIS-R Block Design.
What was found
The annual rate of hippocampal volume loss was significantly higher in APOE-epsilon4 carriers (mean ± SD: 2.32 ± 1.75% per year) compared to non-carriers (0.77 ± 1.02% per year; t = 2.41, p < 0.03). No significant differences between groups were observed across any of the cognitive tests, and hippocampal volume reduction did not correlate with changes on any cognitive measures.
Why it matters
This paper demonstrates that APOE-epsilon4-associated structural brain changes in the hippocampus can be detected longitudinally in middle-aged and older healthy women prior to any measurable decline in memory or cognitive performance.
Limits
The sample size was very small (n = 25 total; only 9 non-carriers), limiting statistical power and increasing the risk of imprecise estimates. The study evaluated only women, so findings cannot be generalized to men. The 2-year follow-up window was relatively brief, which may explain the lack of detectable cognitive changes corresponding to structural volume loss.
Cited by
- supports The volume of the hippocampus declines by approximately 1% to 2% per year in older adults.