## 4 Discussion  
The present results indicated that obesity measurements, blood pressure, and multiple blood biomarkers were significantly correlated with the GM-BHQ. Furthermore, although brain health is influenced by several factors, the current analysis indicated that BMI, \(\gamma\)-GTP, and Glu are related to smaller GM volumes. In the multiple regression analysis, BMI exhibited a higher standardized partial regression coefficient than Glu or SBP. Furthermore, the same tendency was seen in ad-hoc analyses for younger and older participants than the median. Obesity not only leads to an increased incidence of lifestyle-related diseases [21], but also coincides with an increase in the risk of cognitive decline [22] and dementia [23]. Furthermore, brain MRI studies have revealed that obesity and high BMI are linked to decreased GM volume [4; 5; 6]. In obesity, inflammatory responses with subtle glial cell activation have been observed in the central nervous system and are referred to as neuroinflammation without peripheral immune cells [24]. Preclinical animal studies have also shown that high-fat and high-sugar diets are related to neuroinflammationdundancy changes in the brain [25]. These previous studies suggest that obesity leads to a smaller GM volume. Interestingly, a recent study of 15,634 subjects in the UK Biobank showed that the effect of obesity was not mediated by blood pressure and blood biomarkers of glucose, lipids, and C-reactive protein [26]. In other words, obesity itself, rather than obesity-associated high blood pressure, diabetes, hyperlipidemia, or inflammation in peripheral blood, has an effect on GM volume. Thus, preventing obesity can be especially important for brain health care and maintaining GM volume. On the other hand, the cross-sectional results in the present study could not determine a cause-and-effect relationship between smaller GM volumes and obesity. In addition, smaller GM volumes may cause obesity. The previous meta-analysis revealed that obesity is associated with reduced orbitofrontal cortex volume [27]. The orbitofrontal cortex is considered to play an important role in decision making [28] and neural circuits of feeding [29]. Furthermore, glycemicabolism and blood pressure are associated with smaller GM volumes in healthy populations without medications, although a small number of participants were untreated. Interestingly, the present results indicate that reduced GM volume may also be associated with relatively high blood pressure or blood glucose levels that remain within the normal range. In other words, even among individuals without diabetes or hypertension, elevated blood glucose or blood pressure is associated with a smaller GM volume. There are consistent reports of associations between accelerated brain atrophy and patients with type 2 diabetes and hypertension [7; 8; 30]. A few studies have also suggested that prediabetes exerts adverse effects on brain health. Older adults aged over 64 years with prediabetes have a two-fold risk of incident Alzheimer's disease [31]. In women, prediabetic status is associated with brain hypometabolism (as measured using FDG-PET) and poorer executive function and language performance, whereas these associations are not observed in men [32]. Although a previous study reported that prediabetes was not associated with hippocampal atrophy [32], high HbA1C was a risk factor for the progression of whole-brain atrophy, including GM and white matter volume, in a 6-year follow-up study of 201 participants [33]. [PERSON] et al. reported that elevated SBP was associated with reduced GM volumes in 579 healthy young adults (mean age: 39.2 years, SD: 8.4) recruited from a community-based cohort study [9]. Interestingly, Glu exhibited a higher standardization coefficient than SBP in the multiple regression analysis. Thus, Glu may be more strongly associated with GM volume loss than SBP. LDL and HDL are important risk factors for cardiovascular disease, and lowering LDL and maintaining HDL is known to improve cardiovascular outcomes [34].