Effect of Amyloid-Beta load on cognition is modified by the APOE status in a population-based sample of cognitively normal older adults

Abstract

While 30% of cognitively normal older adults have increased b-amyloid (AB) deposition on PET imaging with amyloid ligand [11C]-Pittsburgh Compound B (PiB), the effects of AB load on cognitive function in cognitively normal individuals has been variable. Our objective was to determine the relationship between ß-amyloid (AB) load as measured by [11C]-Pittsburgh Compound B (PiB) PET and cognitive function in cognitively normal older adults. Because both AB load and APOE e4 increase the risk of AD, we further investigated the effects of APOE e4 allele on the association between AB load and cognitive performance. We studied 279 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging (MCSA) from January 2009 through November 2010. The participants underwent amyloid imaging with PiB PET and neuropsychometric testing within 6 months. All partial Spearman rank-order correlations were adjusted for age, sex and education. Voxel-based analysis was performed to determine the pattern of PiB retention that correlates with the global cognitive function in cognitively normal older adults. Higher PiB retention was inversely associated with a measure of overall cognitive performance (r = -0.18; p < 0.01) specifically in the memory and attention/executive function domains in the whole group of participants. The association between PiB retention and cognition was modified by the APOE status in the whole group and in a secondary group analysis matched on PiB retention. In carriers of the APOE e4 allele, higher PiB retention was associated with lower overall cognitive performance (r = -0.46; p < 0.01) specifically in memory, language, attention/executive function and visual-spatial processing. The overall cognitive performance was associated with the AB deposition in the frontal, temporal and parietal lobe association cortices in APOE e4 carriers (Figure). PiB retention was not associated with cognition in APOE e4 non-carriers.Figure. Statistical analyses based on WM tracts in JHU atlas between controls and AD patients. All p < 0.05; red—yellow: 0.05—0 (pvalue). Higher AB load in the frontal, temporal and a parietal lobe association cortex is associated with lower cognitive performance in cognitively normal APOE e4 carriers but not in non-carriers. APOE genotype modifies the influence of AB load on cognitive function in cognitively normal older adults. Associates between global cortical PiB retention and standardized global cognitive scores according to APOE ε4 status (left). Increased PiB retention correlated with global cognitive performance score in the frontal, temporal and parietal association cortices in APOE ε4 carriers as shown in red (right).