## 4 Discussion
However, there was no significant correlation between GM volume and HDL or LDL levels in this study. This result is consistent with that of previous studies. A previous study of 789 older adults also reported no significant correlation between high HDL levels and brain volume [35]. Furthermore, [PERSON] et al. reported that LDL and HDL were not associated with brain volume in 3962 participants [36]. Conversely, [PERSON] et al. also reported that higher levels of small HDL in HDL subclasses were related to smaller brainvolume [36]. The current knowledge on HDL subclasses is limited, although small HDL has been suggested to have more antioxidant and anti-inflammatory properties than lipid-rich large HDL [37]. Further studies are required to elucidate the relationship between brain health and lipid metabolism. The current results indicate that \(\gamma\)-GTP, AST, and ALT are associated with a smaller GM volume. Furthermore, alcoholic liver damage and fatty liver are possible causes of elevated \(\gamma\)-GTP, AST, and ALT levels. Widespread brain atrophy in individuals with alcohol dependence has been consistently documented in MRI studies [38; 39]. Additionally, recent studies suggest that even low to moderate alcohol consumption is a risk factor for brain atrophy [40; 41], although the protective effect of a small amount of alcohol on cognition has also been reported [42]. However, individual differences in alcohol metabolism are well known [43]. Therefore, investigating whether low to moderate alcohol consumption without elevated \(\gamma\)-GTP, AST, and ALT levels is a risk factor for brain atrophy may be of interest to future researchers. Our study has several strengths. The large sample size allowed us to confirm the result by additional analyses divided into two groups according to age. In addition, most of the past studies have been limited to one item [4; 5; 6; 7; 8; 9], but in this study, various measurement items such as obesity, blood pressure, and blood glucose could be used for complex analysis. Furthermore, all participants were examined by general physicians and expert nurses. There are also several limitations to this study. First, SBP values may have been unstable because the data were measured at a medical institution. Furthermore, it is possible that fasting before blood testing was inadequate in a few participants. Second, this was a cross-sectional study, and longitudinal changes in brain atrophy were not followed. Third, the participants in the brain dock system tended to be interested in health, which may have resulted in selection bias due to differences between the included participants and the general community-dwelling population. Fourth, the participants on medication were not evaluated due to a lack of detailed treatment status information. In particular, whether GM volume loss associated with diabetes and hypertension can be suppressed by controlling blood glucose levels and blood pressure is a critical issue. In conclusion, smaller GM volume, which may be an important indicator of brain function, was positively related with following biomarkers: (1) systolic and diastolic blood pressure and heart rate; (2) body mass index, waist circumference, and body fat percentage, (3) blood biomarkers of liver function (AST, ALT, and \(\gamma\)-GTP), uric acid, glycometabolism (Glu and HbA1c), and Ht. Furthermore, the present results suggest that obesity is especially related to smaller GM volumes. The following supporting information can be downloaded at [[https://www.mdpi.com/article/10.3390/jcm11112973/s1](https://www.mdpi.com/article/10.3390/jcm11112973/s1)]([https://www.mdpi.com/article/10.3390/jcm11112973/s1](https://www.mdpi.com/article/10.3390/jcm11112973/s1)). MRI acquisition parameter. Tables for younger and older participants than the median. K.W. : conceptualization, methodology, formal analysis, writing--original draft, writing--review and editing, visualization. S.K. ([PERSON]): conceptualization, writing--review and editing. K.N. : resources, writing--review and editing. K.O.