Changes in glucose metabolism due to aging and gender-related differences in the healthy human brain
Introduction
Understanding age-related and gender-based differences in the function of the brain in healthy subjects is indispensable for investigating psychiatric diseases, which sometimes show significant relationships to age and gender (Buchsbaum and Hazlett, 1997, Flor-Henry, 1978). Studies with [18F]fluoro-deoxy-glucose positron emission tomography (FDG-PET) showed that normal aging is associated with specific patterns of regional cerebral glucose metabolism (Kuhl et al., 1982, Salmon et al., 1991, Loessner et al., 1995, Moeller et al., 1996, Petit-Taboué et al., 1998, Hazlett et al., 1998, Hazlett et al., 2000, Ivançević et al., 2000, Willis et al., 2002). However, it was reported that statistically significant age reductions in regional brain glucose metabolism were not detectable in healthy subjects, after correction for brain atrophy (Ibáñez et al., 2004). A study of normal aging in Japanese subjects also found that the reduction in FDG uptake with advancing age, detected without a correction method for parietal volume effects, could be accounted for largely by age-related cerebral volume loss in perisylvian and medial frontal areas (Yanase et al., 2005). These discrepancies suggested the importance of precise regional measurement and correction for brain atrophy using magnetic resonance imaging (MRI) (de Leon et al., 1987).
In addition, it was reported that functional and morphological changes were affected by gender differences (Coffey et al., 1998). There have been a number of studies of gender differences in brain metabolism, but they were also not consistent (Volkow et al., 1997). FDG-PET studies showed higher global cerebral glucose metabolic rates in females than in males (Baxter et al., 1987, Yoshii et al., 1988, Andreason et al., 1994). Female subjects had a lower glucose metabolic rate than male subjects in the caudate, but an equal rate in the putamen (Brickman et al., 2003). Significant and reproducible gender differences were shown in the cerebellar regions (Volkow et al., 1997). On the other hand, no significant differences were found between young males and females for cerebral glucose metabolism (Miura et al., 1990). Using volumetric MRI and the regional rate of glucose metabolism assessed by PET, a study of gender-related differences and effects of aging showed that metabolic findings cannot be fully explained by sex-related differences in brain atrophy, although this probably accounted for some results (Murphy et al., 1996). Moreover, since glucose metabolism is sensitive to cognitive activity, alterations in age-related cognitive activity may affect the measurement of regional metabolism (Buchsbaum and Hazlett, 1997). Differences in language and culture may also affect age- and gender-related metabolism.
These previous investigations of age- and gender-based differences in brain glucose metabolism using FDG-PET had methodological limitations. In this study we employed a data-extraction technique, the three-dimensional stereotactic surface projections (3D-SSP) method (software library NEUROSTAT; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA) (Minoshima et al., 1995, Burdette et al., 1996, Minoshima et al., 1998, Minoshima, 2003). This method enables improved region identification, quantitative and visual interpretation, and intersubject comparison for groups of subjects in PET examination. It was reported that quantitative accuracy in the 3D-SSP method was less biased by the size of regions or by cortical atrophy than conventional volume of interest (VOI) analysis and Statistical Parametric Mapping (SPM) (Ishii et al., 2001).
The 3D-SSP images and relative glucose metabolic values were acquired in 126 healthy male and female subjects from their twenties to seventies. Previous studies have suggested that some age-related changes in brain structure and metabolism were not linear over the adult age range, but showed accelerated changes in the elderly (Jernigan et al., 1991, Brickman et al., 2003). Therefore, we divided subjects in their twenties to seventies into two groups (subjects in their twenties to forties, and subjects in the fifties to seventies) and examined these two groups. The purpose of this study was to use FDG-PET to investigate age- and gender-related differences in metabolic activity.
Section snippets
Subjects
One hundred twenty-six healthy right-handed Japanese subjects in their twenties to seventies (64 males and 62 females) were examined (Table 1). Subjects more than 40 years old were randomly selected from more than 5000 subjects, who had a health examination for adult diseases with PET and in the Health Science Centre of Fujimoto Hayasuzu Hospital. We selected healthy subjects who had normal blood pressure, no history of alcohol/substance abuse, no psychiatric history including dementia, no
Results
Table 2 provides mean relative metabolic values in subjects in their twenties to seventies at intervals of 10 years. The 3D-SSP Z-score maps showed marked age-related decreases in relative metabolism in the anterior cingulate, medial frontal and left frontal regions, and marked age-related increases in the cerebellum, vermis and central convexity area in both sexes in their twenties and seventies (Fig. 1-A and -B). The 3D-SSP Z-score maps showed sex-related differences between males and females
Discussion
The 3D-SSP method showed changes in regional relative metabolism associated with age- and gender-related differences in the brains of 126 healthy subjects in their 20s to 70s with fewer effects of brain atrophy, size and partial volume effects. The 3D-SSP Z-score map demonstrated marked decreases in relative metabolism in the anterior cingulate, medial frontal and left frontal regions, and marked increases in the cerebellum, vermis and central convexity area in the combined gender group in
Acknowledgement
We acknowledge the valuable suggestions of Prof. Toshifumi Nomachi, Miyakonojo Technical College for the statistical analysis in this study.
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