P1-277: Examining the regional specificity between Aβ burden and cognition

Abstract

A correlation between neocortical beta-amyloid (Aβ) burden and episodic memory has been previously reported in nondemented individuals but not in Alzheimer's disease (AD; Pike et al., 2007). This issue was reexamined using twice as many participants. The regional specificity of the relationship between Aβ burden and cognition was also examined. Eighty-eight healthy controls (HC), 54 mild cognitive impairment (MCI), and 52 AD participants were studied. Aβ burden was quantified 40–70 min post-PiB injection using Standardized Uptake Value normalized to cerebellar cortex for neocortex as well as for specific regions including parietal, medial temporal, and frontal regions. Composite episodic memory and nonmemory scores were calculated using 46 PiB negative healthy controls with normal MRI as the reference. In addition, “frontal”, “medial temporal”, and “parietal” composite scores were constructed from cognitive tasks predominantly reliant on executive functions, episodic memory, and visuospatial skills, respectively. There were strong correlations between neocortical Aβ and both memory (r=-.67, p<.001) and nonmemory (r=-.47, p<.001) performance across all groups. When groups were analysed separately, the relationship between memory and neocortical amyloid burden remained significant in the MCI (r=-.58, p<.001) and HC groups (r=-.21, p=0.047). In contrast, there was no relationship between memory and Aβ burden in AD (r=.02). Nonmemory scores did not correlate with amyloid burden for any group. Regarding regional specificity, when all participants were examined the expected regional correlations were present – although for all composite scores the strongest relationship was with parietal Aβ burden. The “parietal” and “frontal” composite scores did not relate to Aβ burden in any region when groups were analysed separately. In nondemented participants, although the “medial temporal” composite score correlated with Aβ burden, it did not demonstrate regional specificity, showing the strongest correlations with parietal and medial temporal Aβ burden in MCI (both r=-.56, p<.001) and superior frontal Aβ burden in HCs (r=-.25, p=.02). The relationship between cognition and PiB uptake is not regionally specific. The strong relationship between episodic memory impairment (the earliest cognitive change in AD) and PiB uptake in nondemented individuals supports the notion that PiB-PET can detect AD prior to development of dementia.