AGEING NEUROREPORT 0959-4965 & Lippincott Williams & Wilkins Vol 12 No 11 8 August 2001 2315 1 H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging Marco Catani, 1,3,CA Antonio Cherubini, 1 Robert Howard, 3 Roberto Tarducci, 2 GianPiero Pelliccioli, 4 Massimo Piccirilli, 5 Gianni Gobbi, 2 Umberto Senin 1 and Patrizia Mecocci 1 1 Institute of Gerontology and Geriatrics and 5 Clinical Psychology and Psychiatry Section, University of Perugia; 2 Department of Physics, Monteluce Hospital, Perugia, Italy; 3 Section of Old Age Psychiatry, Institute of Psychiatry, London SE5 8AF, UK; 4 Department of Neuroradiology, Silvestrini Hospital, Perugia, Italy CA,3 Corresponding Author and Address Received 28 March 2001; accepted 25 May 2001 This study aimed to characterize the white matter biochemical pro®le of healthy elderly subjects, mild cognitive impairment (MCI) subjects, and early Alzheimer's disease (AD) patients. We used proton magnetic resonance spectroscopy ( 1 H-MRS) to measure myo-inositol, creatine, N-acetylaspartate (NAA) and choline levels from a volume of interest located in the paratrigonal white matter bilaterally. A signi®cantly higher myo- inositol/creatine ratio was found in MCI subjects and AD patients than in controls. The NAA/creatine ratio was reduced in AD patients in the left hemisphere compared to control subjects. The choline/creatine ratio was not signi®cantly differ- ent among the three groups. These data suggest that MCI is different from normal brain aging, having a white matter biochemical pattern similar to AD. NeuroReport 12:2315±2317 & 2001 Lippincott Williams & Wilkins. Key words: 1 H magnetic resonance spectroscopy; Mild cognitive impairment; Myo-inositol INTRODUCTION Increasing attention has been devoted in recent years to elderly subjects suffering from a cognitive impairment greater than would be expected to accompany normal aging, but insuf®cient to ful®l diagnostic criteria for dementia. Among the entities that have been proposed to characterize these subjects, mild cognitive impairment (MCI) has received a great deal of recent interest [1]. We do not know whether MCI represents the prediagnosis phase of Alzheimer's disease (AD), those individuals with the most severe age-related memory decline or a mixture of subjects with either or both of these problems. A recent longitudinal study has shown that subjects with MCI have a poorer cognitive prognosis than healthy elderly subjects, with a conversion rate of 12% per year to AD [2]. Several studies have attempted to characterize the differences between MCI and normal aging. A neuropathological study showed that subjects with MCI have a range of histological ®ndings, from those seen in normal brain aging to those that characterize AD [3]. CT has demonstrated a smaller medial temporal lobe volume in MCI subjects than in the normal elderly [4]. A single photon emission computed tomography (SPECT) study has shown that temporo-parietal perfusion in MCI subjects is intermediate between that seen in normal elderly subjects and AD patients [5]. Quantitative electroencephalography has demonstrated a similar pattern in AD and MCI patients, clearly different from that observed in normal elderly subjects [6]. Recently Kantarci et al., using proton magnetic resonance spectroscopy ( 1 H-MRS), have shown an increase in the gray matter myo-inositol/creatine ratio in MCI subjects compared with normal controls and in AD pa- tients compared to MCI and controls [7]. The data on possible biological markers are more scanty [1]. 1 H-MRS is a technique which measures brain metab- olites (N-acetylaspartate (NAA), myo-inositol, choline, creatine) in vivo. NAA is found primarily in neuronal membranes and therefore is considered a marker of neur- onal (or axonal) density. Myo-inositol is a precursor of the inositol polyphosphate messenger system. The choline resonance re¯ects the contribution of several cytosolic cho- line-containing compounds. The creatine signal is usually stable over time and therefore is often used as an internal standard to which the resonance intensities of the other metabolites are normalized. The aim of this study was to evaluate the white matter biochemical pattern of healthy elderly subjects, MCI sub- jects, and early AD patients using 1 H-MRS. SUBJECTS AND METHODS All subjects were aged > 70 years. Subjects underwent a clinical and functional examination, and a neuropsycho-