Elsevier

Neurobiology of Aging

Volume 30, Issue 3, March 2009, Pages 353-363
Neurobiology of Aging

Review
A systematic review of brain metabolite changes, measured with 1H magnetic resonance spectroscopy, in healthy aging

https://doi.org/10.1016/j.neurobiolaging.2007.07.005Get rights and content

Abstract

Background

1H MR spectroscopy (MRS) can identify metabolite abnormalities in age-related, neurological diseases. However, there is little information on how metabolites change with healthy aging.

Methods

We systematically reviewed the literature on MRS, from 1980 to 2006, for studies where healthy young subjects (<60 years) were compared to healthy older subjects (>60 years). We extracted metabolite data reported as “no change”, “increase” or “decrease” for each metabolite by brain region and, where data were available, meta-analysed mean metabolite concentrations (mM) for young versus old subjects.

Results

Eighteen studies met the inclusion criteria (total n = 703 subjects, 284 >60 years old). Most data came from the frontal region, and reported “no change” in older subjects; however, a meta-analysis revealed a decrease in frontal NAA (p = 0.05) and increases in parietal choline (p = 0.003) and creatine (p < 0.001).

Discussion

These data suggest that NAA may decrease and choline and creatine increase with age. Therefore, more data are needed from older subjects to characterise age effects better and ratios in older subjects should be interpreted with caution.

Introduction

Average life expectancy has increased from 65.6 years for men and 71.1 for women in 1950, to 74.8 for men and 80.1 for women in 2003 (Hoyert et al., 2005). Assuming that health care continues to improve; then the proportion of older persons in the general population is expected to double, worldwide, over the next 50 years. The numbers of those developing neurological diseases associated with aging, such as stroke and the dementias, is also likely to increase.

1H magnetic resonance spectroscopy (MRS), is a non-invasive method of studying cerebral metabolites associated with age-related, neurological diseases such as stroke (Duijn et al., 1992, Moreno-Torres et al., 2005), the dementias (Alzheimer's, Heun et al., 1997, Jessen et al., 2000; vascular dementia, Charles et al., 1994), mild cognitive impairment (Kantarci et al., 2004, Kantarci et al., 2006) and Parkinson's disease (Ellis et al., 1997). The most commonly studied metabolites include N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myoinositol (MI), and more rarely, glutamate (Glu), glutamine (Gln), lacate (Lac) and gamma-amino butyric acid (GABA). These metabolites may provide information on developing abnormalities, sometimes prior to, or in the absence of, clinical features (Godbolt et al., 2006).

MRS allows for the safe monitoring of disease progression over time through repeated scanning, and therefore is often used in studies focused on the early detection of disease (Parsons et al., 2000) or differential diagnoses (Herminghaus et al., 2003, Kantarci et al., 2006). Longitudinal studies of this nature are extremely valuable in identifying and monitoring disease-related changes, however, they are also vulnerable to systematic changes in brain metabolites over time that may be associated with healthy aging rather than disease progression. There are, to date, no normative values available for the major brain metabolites in healthy, older subjects. This lack of data makes it difficult to distinguish between disease-related changes and normal aging, particularly prior to obvious clinical manifestations. Therefore, we performed a systematic review of the literature on 1H MRS metabolites in older subjects, to summarize available cerebral metabolite data and to determine whether metabolites change during the course of “healthy aging”.

Section snippets

Search strategy

We used methodology for performing systematic reviews as published by the Cochrane Collaboration (Higgins and Green, 2005). We searched MEDLINE and EMBASE from January 1980 to March 2006 for publications in any language using the search terms: “spectroscopy”, “magnetic resonance spectroscopy”, “MRS”, “spectroscopic imaging”, “brain”, “ageing”, “aging” (US), “proton” and “1H”. Only those papers which presented original data were included, although we searched the reference lists of published

Search results

We identified 231 potentially relevant studies in the literature and excluded 207 (Fig. 1). Of the remaining 24 studies, we excluded six because either the metabolite data were not presented according to age group (Bartha et al., 2000, Kaiser et al., 2005, Valenzuela et al., 2000); or only the NAA/(creatine + choline) ratio was reported (Szenkuti et al., 2004); or only grey/white matter metabolite ratios (e.g. NAAGM/NAAWM) were reported (Lim and Spielman, 1997, Pfefferbaum et al., 1999).

Characteristics of included papers

Table 1

Discussion

Despite increased application of in vivo1H MRS to study age-related neurological and psychological diseases, this review shows that there are few data on metabolite values for older people (>60 years). It is well established that metabolite concentrations can vary between brain regions (Angelie et al., 2001, Kreis et al., 1993) and in different tissue types (WM versus GM) (Noworolski et al., 1999). There is also an observable and region-specific reduction in brain tissue volume with age (Lim et

Conflict of interest

The authors have no conflicts of interest to declare.

Acknowledgements

Dr. Kristin Haga is funded by research fellowships from “Research into Aging” and the “National Alliance for Research into Schizophrenia and Depression” (NARSAD).

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