Abstract
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Objectives To examine the role that brain pH plays as a mechanistic link underlying the development of Alzheimer’s Disease (AD) by characterizing the cerebral microenvironment with imaging measures sensitive to pH and cellular metabolism (e.g., glucose, lactate) across the spectrum of cognitive function and amyloid burden.
Methods Participants, across the spectrum of cognitive function from healthy control to mild AD, underwent [18F]fluorodeoxyglucose (FDG) imaging for characterization of glucose metabolism, [11C]PIB (PIB) for assessment of amyloid burden and T1-weighted, T2-weighted, T1rho (spin lattice relaxation in the rotating frame) MR imaging for structural and pH-related measures. Recent work by Magnotta, et al. evaluated the use of T1rho MRI to examine brain pH (higher T1rho=lower pH=more acidic). Cognitive status was determined by neuropsychological testing.
Results Participants (N=10, 6F,4M, age 55-90 yrs, 4 HC, 4 eMCI, 1 lMCI, 1 AD) were studied. Globally, the T1rho signal was negatively correlated with the FDG-based measure of glucose metabolism (r=-0.69, p=0.03 uncorrected), positively correlated with the amyloid burden (cortical retention ratio) (r=0.79, p<0.01 uncorrected), negatively correlated with the logical memory score (both immediate and delayed) (r=-0.81 and -0.66, p<0.01 and 0.04,uncorrected) and positively correlated with Trailmaking Test B-A times (r=0.63, p=0.05, uncorrected). The brain T1rho signal was consistent with a more acidic environment with increasing age with further enhanced signal in the AD participant. For AD-associated cortical regions, the median regional T1rho signal was positively correlated with the PIB SUVR and DVR (SRTM2) and negatively correlated with FDG SUV with and without correction for the blood glucose level (p<0.005 for all comparisons).
Conclusions In older participants, higher T1rho signals (pH sensitive measure) in the brain were associated with lower glucose metabolism, higher amyloid burden and poorer cognitive performance.
Research Support Biological Sciences Funding Program (BSFP), Office of Vice President for Research, University of Iowa