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Date of Award

Spring 3-24-2014

Author's School

College of Arts & Sciences

Author's Department/Program

Biology

Abstract

Elevated levels of amyloid, as detected by elevated uptake of PET tracer 11C Pittsburgh Compound B (PIB), are thought to represent a preclinical stage of Alzheimer’s Disease (AD). We sought to analyze whether cortical thickness and white matter integrity changes can be identified in participants who have longitudinal increases in PIB. 91 asymptomatic adults (Clinical Dementia Rating (CDR) = 0, mean age 63.1 years, 63f) had PIB PET scans ~2.6 years apart. All participants remained asymptomatic (CDR = 0) throughout the duration of the study. Mean cortical binding potential (MCBP) was calculated for each scan, and all participants were PIB-negative (MCBP<0.18) at baseline. Volumetric MRI and diffusion tensor imaging (DTI) were obtained at the time of the second PIB scan. Increases in MCBP were associated with elevated cortical thickness predominantly in the temporal lobe but also involving the posterior frontal lobe and occipital lobe. Additionally, longitudinal increases in MCBP were associated with lower apparent diffusion coefficient but no change in fractional anisotropy. Our findings suggest that increasing levels of amyloid deposition, even when below established thresholds for “PIB positivity,” are not benign. A second question of interest was whether a clinical measure of white matter damage predicts cognitive impairment better than measures of amyloid deposition alone. Using the Fazekas scale we quantified white matter damage in 459 participants (mean age 68.3 years, 269f) who were cognitively normal (CDR=0, n=397), very mildly impaired (CDR=0.5, n=51), or mildly impaired (CDR=1.0, n=11). Amyloid was measured using PIB PET scans. We found a significant association between cognitive status and age, gender, amyloid deposition, as well as score on the Fazekas scale. This suggests that the Fazekas scale is a useful clinical measure for diagnosing AD.

Language

English (en)

Advisor/Committee Chair

Tammie Benzinger

Advisor/Committee Chair's Department

Radiology

Second Advisor

Marcus Raichle

Second Advisor's Department

Radiology

Third Advisor

Brian Gordon

Third Advisor's Department

Radiology