Association of Sub-Threshold Amyloid Retention With Neuropsychological Performance in Cognitively Normal Older Adults Without the APOE ε4 Allele

ABSTRACT

Objective@#Recent evidence shows that the quantitative value of amyloid-beta (Aβ) deposition below the threshold of Aβ positivi-ty carries biological and clinical significance regarding future cognitive decline. We evaluated whether the quantitative value of sub-threshold Aβ deposition had a significant correlation with neuropsychological test scores in cognitively normal older adults without the APOE ε4 allele. @*Methods@#Sixty cognitively normal APOE ε4 allele non-carriers with negative Aβ retention aged 60 to 85 years were included in this study. We assessed neuropsychological performance with the Korean version of the Consortium to Establish a Registry for Al-zheimer’s Disease (CERAD-K) and obtained standardized [ 18 F] flutemetamol uptake values in the pons as a reference (SUVR PONS), evaluated with PET. Multiple regression analyses were conducted to assess the effect of global and regional Aβ load on cognitive performance, adjusting for age, sex, years of education, and volumes of white matter hyperintensities. @*Results@#We found that Aβ deposition in the precuneus, posterior cingulate cortex, and parietal lobe had a significant association with the total CERAD-K scores. There was also a significant correlation between the SUVR PONS in the precuneus and the CERAD-K total score after Bonferroni correction. @*Conclusion@#Subthreshold Aβ retention in the core brain regions of the default mode network could affect cognitive functions in the cognitively normal APOE ε4 non-carriers, considered to be the lowest risk group for Alzheimer’s disease (AD).