Abstract
Objective: To assess whether noninvasive proton magnetic resonance spectroscopy (H-1-MRS) tissue metabolite measurements at baseline can predict an increase in the rate of beta-amyloid (A beta) accumulation on serial PET in clinically normal (CN) older adults. Methods: Consecutive participants aged 60 years and older (n = 594) from the Mayo Clinic Study of Aging who were CN at baseline and who underwent H-1-MRS from the posterior cingulate voxel and longitudinal C-11-Pittsburgh compound B (PiB)-PET were included.
The rate of A beta accumulation by serial cortical PiB standardized uptake value ratios was estimated as a function of baseline H-1-MRS metabolite ratios and time using mixed-effect models adjusted for age, sex, and APOE epsilon 4. Effect of APOE epsilon 4 on the relationship between baseline MRS and an increased rate of A beta accumulation was also assessed.
Results: Among all participants, a higher myo-inositol (mI)/creatine (p = 0.011) and a lower Nacetylaspartate/mI (p = 0.006) at baseline were associated with an increased A beta accumulation over time after adjusting for age, sex, and APOE epsilon 4. APOE epsilon 4 did not modify the association of baseline H-1-MRS metabolite ratios and rate of A beta accumulation.
However, APOE epsilon 4 carriers accumulated A beta faster than noncarriers regardless of the baseline A beta load (p = 0.001). Conclusion: Among CN older adults, early metabolic alterations on H-1-MRS and APOE epsilon 4 status are independently associated with an increased rate of A beta accumulation.
Our findings could have important implications for early diagnosis and identification of individuals for secondary prevention trials, because an increased rate of A beta accumulation in CN older adults may confer a higher risk for cognitive decline and mild cognitive impairment.