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Adolf Pfefferbaum, MD; Elfar Adalsteinsson, PhD; Daniel Spielman, PhD; Edith V. Sullivan, PhD; Kelvin O. Lim, MD

Arch Gen Psychiatry. 1999;56:185-192.

Background  Alzheimer disease (AD) and normal aging result in cortical gray matter volume deficits. The extent to which the remaining cortex is functionally compromised can be estimated in vivo with magnetic resonance spectroscopic imaging.

Objective  To assess the effects of age and dementia on gray matter and white matter concentrations of 3 metabolites visible in the proton spectrum: N-acetyl compounds, present only in living neurons; creatine plus phosphocreatine, 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 spectroscopic imaging and memory and language testing.

Results  Gray matter N-acetyl compound concentrations (signal intensity corrected for the amount of brain tissue contributing to the magnetic resonance 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 higher in the elderly than the younger controls, and even higher in the AD group than in the elderly control group. Functional significance of these findings was supported by correlations between poorer performance on recognition memory tests and lower gray matter N-acetyl compounds in elderly controls and higher gray matter creatine plus phosphocreatine and choline concentrations in patients with AD.

Conclusion  Cortical gray matter volume deficits in patients with AD are accompanied by disease-related increases in gray matter choline concentrations suggestive of cellular degeneration and reduced N-acetyl compound concentrations, with possible effects on behavioral function.

From the Neuropsychiatry Program, SRI International, Menlo Park (Dr Pfefferbaum); Departments of Psychiatry and Behavioral Sciences (Drs Pfefferbaum and Sullivan) and Radiology (Drs Adalsteinsson and Spielman), Stanford University School of Medicine, Stanford, Calif; and the Nathan Kline Institute, Orangeburg, NY (Dr Lim).

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