Preferential preservation of constructional praxis delayed recall compared to word list delayed recall in the Amish

Abstract

While studying cognition in the Amish, we have observed strong performance on the constructional praxis delayed recall (CPDR) as compared to other cognitive tests, independent of overall cognitive status. This may indicate a preferential preservation of visuoconstructive memory in this population. Here, we investigate this by comparing the CPDR to the word list delayed recall (WLDR) while controlling for relationship, genetic risk of Alzheimer disease, and other covariates.Amish individuals > 65 years of age (mean age=82) in Indiana/Ohio were examined (n=512) and assigned by consensus review to Normal, MCI/Borderline, or Impaired cognitive status. Paired t-tests were used to compare the CPDR and WLDR Z-scores. Using genome-wide genotype data, a kinship matrix and principal components (PCs) estimating population substructure were calculated. Genetic Risk Scores (GRS) were also calculated using genome-wide significant variants from Kunkle et al. (2019), weighted by log odds ratio estimates. Using linear regression adjusting for relatedness, we modeled the contribution of GRS, PC1, PC2, cognitive status, age, sex, and education level to the difference between the CPDR and WLDR Z-scores.We found a significantly better performance on CPDR over WLDR in every cognitive status group, with this difference between Z-scores being 1.02 units for Normal, 1.72 units for MCI/Borderline, and 1.58 units for Impaired. Linear regression of this difference in Z-scores found significant associations with age, sex, and cognitive status. The effect size of cognitive status was 0.65 units for MCI/Borderline and 0.50 units for Impaired, with Normal as the reference category. This indicates that MCI/Borderline and Impaired individuals have a significantly larger gap between CPDR and WLDR Z-scores than Normal individuals.These results suggest that the Amish may preserve memory of constructional praxis relative to word list, especially in MCI/Borderline and Impaired individuals. This indicates that impaired Amish individuals, including those with Alzheimer disease, may decline at a slower rate in visuoconstructive memory than other domains. Genetic Risk Score was not significantly associated with this preferential preservation of constructional praxis, suggesting that it may not be explained by known risk genes. This warrants further studies to identify genetic and other factors associated with this preferential preservation.