Neurometabolic topography and associations with cognition in Alzheimer's disease: A whole-brain high-resolution 3D MRSI study

INTRODUCTION: Altered neurometabolism, detectable via proton magnetic resonance spectroscopic imaging (¹H-MRSI), is spatially heterogeneous and underpins cognitive impairments in Alzheimer's disease (AD). However, the spatial relationships between neurometabolic topography and cognitive impairment in AD remain unexplored due to technical limitations. METHODS: We used a novel whole-brain high-resolution ¹H-MRSI technique, with simultaneously acquired ¹⁸F-florbetapir positron emission tomography (PET) imaging, to investigate the relationship between neurometabolic topography and cognitive functions in 117 participants, including 22 prodromal AD, 51 AD dementia, and 44 controls. RESULTS: Prodromal AD and AD dementia patients exhibited spatially distinct reductions in N-acetylaspartate, and increases in myo-inositol. Reduced N-acetylaspartate and increased myo-inositol were associated with worse global cognitive performance, and N-acetylaspartate correlated with five specific cognitive scores. Neurometabolic topography provides biological insights into diverse cognitive dysfunctions. DISCUSSION: Whole-brain high-resolution ¹H-MRSI revealed spatially distinct neurometabolic topographies associated with cognitive decline in AD, suggesting potential for noninvasive brain metabolic imaging to track AD progression. Highlights: Whole-brain high-resolution ¹H-MRSI unveils neurometabolic topography in AD. Spatially distinct reductions in NAA, and increases in mI, are demonstrated. NAA and mI topography correlates with global cognitive performance. NAA topography correlates with specific cognitive performance.