Brain amyloid burden and cerebrovascular disease are synergistically associated with neurometabolism in cognitively unimpaired older adults.

Alzheimer's disease (AD) is the most common cause of cognitive dysfunction in older adults. The pathological hallmarks of AD such as beta amyloid (Aβ) aggregation and neurometabolic change, as indicated by altered myo-inositol (mI) and N-acetylaspartate (NAA) levels, typically precede the onset of cognitive dysfunction by years. Furthermore, cerebrovascular disease occurs early in AD, but the interplay between vascular and neurometabolic brain change is largely unknown. Thirty cognitively normal older adults (age = 70 ± 5.6 years, Mini-Mental State Examination = 29.2 ± 1) received 11-C-Pittsburgh Compound B positron emission tomography for estimating Aβ-plaque density, 7 Tesla fluid-attenuated inversion recovery magnetic resonance imaging for quantifying white matter hyperintensity volume as a marker of small vessel cerebrovascular disease and high-resolution magnetic resonance spectroscopic imaging at 7 Tesla, based on free induction decay acquisition localized by outer volume suppression to investigate tissue-specific neurometabolism in the posterior cingulate and precuneus. Aβ (β = 0.45, p = 0.018) and white matter hyperintensities (β = 0.40, p = 0.046) were independently and interactively (β = -0.49, p = 0.026) associated with a higher ratio of mI over NAA (mI/NAA) in the posterior cingulate and precuneus gray matter but not in the white matter. Our data suggest that cerebrovascular disease and Aβ burden are synergistically associated with AD-related gray matter neurometabolism in older adults.