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Abstract INTRODUCTION Altered neurometabolism, detectable via proton magnetic resonance spectroscopic imaging ( 1 H‐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 1 H‐MRSI technique, with simultaneously acquired 18 F‐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 1 H‐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 1 H‐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.
Hu et al. (Mon,) studied this question.