In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease

Background: Alzheimer disease (AD) and normal aging result in cortical gray matter volume deficits. The extent to which the remaining cortex is functi onally compromised can be estimated in vivo with magnetic resonance spectro scopic imaging. Objective: To assess the effects of age and dementia on gray matter and whi te matter concentrations of 3 metabolites visible in the proton spectrum: N -acetyl compounds, present only in living neurons; creatine plus phosphocre atine, reflecting high-energy phosphate metabolism; and choline, increasing with membrane synthesis and degradation. Method: Fifteen healthy young individuals, 19 healthy elderly individuals, and 16 patients with AD underwent 3-dimensional magnetic resonance spectros copic imaging and memory and language testing. Results: Gray matter N-acetyl compound concentrations (signal intensity cor rected for the amount of brain tissue contributing to the magnetic resonanc e spectroscopic imaging signal) was significantly reduced only in patients with AD, even though both the AD and elderly control groups had substantial gray matter Volume deficits relative to the young control group. Both the healthy elderly and AD groups had abnormally high gray matter creatine plus phosphocreatine concentrations. Gray matter choline concentrations were hi gher in the elderly than the younger controls, and even higher in the AD gr oup than in the elderly control group. Functional significance of these fin dings was supported by correlations between poorer performance on recogniti on memory tests and lower gray matter N-acetyl compounds in elderly control s and higher gray matter creatine plus phosphocreatine and choline concentr ations in patients with AD. Conclusion: Cortical gray matter volume deficits in patients with AD are ac companied by disease-related increases in gray matter choline concentration s suggestive of cellular degeneration and reduced N-acetyl compound concent rations, with possible effects on behavioral function.