Optimal memory performance in older adults is associated with differences in hippocampal volume and amyloid status at baseline and over 3 years

Age-related declines in memory have been well-documented. However, some individuals reach their 8th -10th decade while maintaining strong memory performance. We were interested in which demographic and biomarker variables distinguished individuals aged 75+ who score in the top 20th percentile for memory (Optimal Agers) from their typically scoring peers (Typical Agers). A total of 125 clinically healthy older adults (CDR=0; MMSE: 28.78±1.07) aged 75-90 from the Harvard Aging Brain Study underwent annual memory testing and neuroimaging (MRI and PET amyloid) at baseline and 3-year follow-up. A memory composite score was derived from standardized and challenging tests including the 6-Trial Selective Reminding Test, Memory Capacity Test, and Face-Name Associative Memory Exam. Participants were grouped into Optimal Agers (n=25) vs. Typical Agers (n=100) based on their memory composite scores. Follow-up data available on 20 of the 25 Optimal Agers revealed that 12 individuals maintained their optimal status (Optimal Maintainers) while 8 declined compared to their initial performance (Optimal Non-Maintainers). T-tests, Mann Whitney U tests, and χ2 tests were used to compare groups on β-amyloid accumulation, and ICV-adjusted hippocampal volume. There were no group differences in demographics. At baseline, Optimal Agers tended to have larger hippocampal volumes (ICV adjusted Vol=7319.82) compared with Typical Agers (ICV adjusted Vol= 6917.12) (t(123)=-2.79 p=0.01). At 3-year follow-up, those who maintained their optimal status had lower amyloid levels at baseline (mean DVR=1.18) in contrast to Non-Maintainers (mean DVR= 1.46) (U=20, p=0.031). Optimal Maintainers also had lower rates of amyloid accumulation (0.02 DVR/year) compared to Non-Maintainers (0.05 DVR/ year)) (t(16)=2.45, p=0.026). Optimal memory performance in those 75+ years of age was associated with larger hippocampi at baseline. Those who maintained optimal performance over 3 years had lower amyloid levels and lower rates of amyloid accumulation but no difference in hippocampal volumes. Understanding factors associated with brain resilience may help better predict an individual’s dementia trajectory.