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However, the spatial relationships between neurometabolic topography and cognitive impairment in AD remain unexplored due to technical limitations.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We used a novel whole\u2010brain high\u2010resolution <jats:sup>1<\/jats:sup>H\u2010MRSI technique, with simultaneously acquired <jats:sup>18<\/jats:sup>F\u2010florbetapir 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Prodromal AD and AD dementia patients exhibited spatially distinct reductions in N\u2010acetylaspartate, and increases in myo\u2010inositol. Reduced N\u2010acetylaspartate and increased myo\u2010inositol were associated with worse global cognitive performance, and N\u2010acetylaspartate correlated with five specific cognitive scores. Neurometabolic topography provides biological insights into diverse cognitive dysfunctions.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Whole\u2010brain high\u2010resolution <jats:sup>1<\/jats:sup>H\u2010MRSI revealed spatially distinct neurometabolic topographies associated with cognitive decline in AD, suggesting potential for noninvasive brain metabolic imaging to track AD progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Whole\u2010brain high\u2010resolution <jats:sup>1<\/jats:sup>H\u2010MRSI unveils neurometabolic topography in AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Spatially distinct reductions in NAA, and increases in mI, are demonstrated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NAA and mI topography correlates with global cognitive performance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NAA topography correlates 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