RYAN O'DELL, United States of America
Yale School of Medicine PsychiatryAuthor Of 1 Presentation
SYNAPTIC DENSITY IS ASSOCIATED WITH COGNITIVE PERFORMANCE IN EARLY ALZHEIMER’S DISEASE: A PET IMAGING STUDY WITH [11C]UCB-J
Abstract
Aims
Synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer’s disease (AD); however, this statement is based on limited neuropathological study. In this study we examined the relationship between synaptic density and cognitive performance in early AD using [11C]UCB-J PET and an extensive neuropsychological battery.
Methods
[11C]UCB-J binding was measured in 45 amyloid+ participants with AD (17 amnestic MCI and 28 mild dementia) and 20 amyloid– cognitively normal participants aged 50-85. Synaptic density was calculated as the distribution volume ratio (DVR) in a composite of AD-affected regions, using cerebellum as reference region. A neuropsychological battery assessed performance in five cognitive domains. Domain scores were generated for each AD participant by averaging z-scores within the domain, and global cognitive scores averaged the domain scores.
Results
In a multiple linear regression model controlling for age, sex, and education, synaptic density ([11C]UCB-J DVR) was a significant predictor of global cognitive performance in participants with AD (β=3.21, η2=0.29, P=0.0001; Figure 1A), as well as Verbal Memory (P=0.022; Figure 1B), Language (P=0.001; Figure 1C), Executive Function (P=0.001; Figure 1D), Processing Speed (P=0.001; Figure 1E), and Visuospatial Ability (P=0.001; Figure 1F). The association between synaptic density and global cognition survived partial volume correction (β=2.16, η2=0.23, P=0.001), and synaptic density was a stronger predictor of cognitive performance than gray matter volume.
Conclusions
These results confirm neuropathologic studies, demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the early stages of AD.