Longitudinal Effects of Amyloid on Cognitive Decline in Middle-Aged and Older Adults

Understanding the role of amyloid pathology in cognitively normal adults is of utmost importance to the potential treatment and prevention of Alzheimer’s disease. The present dissertation utilizes PET imaging with the tracer florbetapir at baseline and after a four year follow-up in cognitively normal adults from the Dallas Lifespan Brain Study to assess the impact of baseline mean cortical amyloid burden and change in regional amyloid burden on cognitive decline. Study 1 demonstrated a dose-response relationship between the magnitude of amyloid burden at baseline and the rate of cognitive decline over a four-year follow-up, particularly for episodic memory. These results suggest that the magnitude of amyloid deposition at baseline predicts those likely to be on a more pathological cognitive trajectory, potentially heading towards dementia. Additionally, Study 2 demonstrated a regionally specific relationship between the rate of amyloid accumulation over four years across multiple posterior regions and episodic memory decline. These findings demonstrate the importance of assessing regional changes in amyloid to monitor disease progression. Additionally, secondary analyses were conducted in middle-aged adults (age 30-59) and initially amyloid negative adults to assess whether a relationship between amyloid and cognitive decline is apparent both early in the lifespan as well as early in disease progression. In Study 1, relatively high baseline mean cortical amyloid burden compared with one’s peers was not predictive of cognitive decline in either group. In contrast, Study 2 was able to leverage longitudinal changes in amyloid in middle-aged and initially amyloid negative individuals to detect early amyloid-related changes in episodic memory across multiple posterior regions including the posterior cingulate, parietal and occipital lobes. Consequently, it may be useful to focus on these regions in both research and clinical trials aimed at early intervention of Alzheimer’s disease.