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Published online before print March 26, 2008, doi:10.1212/01.wnl.0000306314.77311.be)
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Volume 70, Number 18, April 29, 2008
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Received September 10, 2007
Accepted December 14, 2007

Hippocampal neurochemistry, neuromorphometry, and verbal memory in nondemented older adults

M. E. Zimmerman PhD*, J. W. Pan MD, PhD, H. P. Hetherington PhD, M. J. Katz MPH, J. Verghese MD, H. Buschke MD, C. A. Derby PhD, and R. B. Lipton MD

From the Saul R. Korey Department of Neurology (M.E.Z., M.J.K., J.V., H.B., C.A.D., R.B.L.), Albert Einstein College of Medicine, Bronx, NY; and Department of Neurosurgery (J.W.P., H.P.H.), Yale University School of Medicine, New Haven, CT.


* To whom correspondence should be addressed. E-mail: mzimmerm{at}aecom.yu.edu.

Background: Characterization of the behavioral correlates of neuromorphometry and neurochemistry in older adults has important implications for an improved understanding of the aging process. The objective of this study was to test the hypothesis that a measure of hippocampal neuronal metabolism was associated with verbal memory in nondemented older adults after controlling for hippocampal volume.

Methods: 4-T MRI, proton magnetic resonance spectroscopy (1H MRS), and neuropsychological assessment were conducted in 48 older adults (23 women; mean age 81 years). Average hippocampal N-acetyl aspartate/creatine ratios (NAA/Cr) and hippocampal volumes were obtained. Neuropsychological evaluation included tests of verbal memory (Buschke and Grober Free and Cued Selective Reminding Test–Immediate Recall [FCSRT-IR], Wechsler Memory Scale–Revised Logical Memory subtest) and attention and executive function (Trail Making Test Parts A and B).

Results: Linear regression analysis indicated that after adjusting for age, hippocampal NAA/Cr was a significant predictor of FCSRT-IR performance ({beta} = 0.38, p = 0.01, R 2 = 0.21). Hippocampal volume was also a significant predictor of FCSRT-IR performance after adjusting for age and midsagittal area ({beta} = 0.47, p = 0.01, R 2 = 0.24). In a combined model, hippocampal NAA/Cr ({beta} = 0.33, p = 0.03) and volume ({beta} = 0.35, p = 0.03) were independent predictors of FCSRT-IR performance, accounting for 30% of the variance in memory.

Conclusions: These findings indicate that nondemented older adults with smaller hippocampal volumes and lower levels of hippocampal N-acetyl aspartate/creatine ratio metabolites perform more poorly on a test of verbal memory. The integrity of both the structure and metabolism of the hippocampus may underlie verbal memory function in nondemented elderly.




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