Differential brain volume between obese and underweight cognitively normal older adults with frailty in the JPSC-AD

Abstract

Frailty is common in older adults; however, the central nervous system mechanisms underlying the differences between obesity and underweight remain unclear. This study investigated brain volume in frail, cognitively normal, community-dwelling older adults across three body mass index (BMI) groups: low (< 18.5), intermediate (18.5-24.9), and high (≥ 25.0). Whole and regional brain volumes were measured and analyzed. Among 3,627 participants, those in the high BMI group (n = 1,134) had significantly lower multivariate-adjusted total brain volume (66.8% vs. 67.3%, p < 0.001) and gray matter volume (36.1% vs. 36.6%, p < 0.001) than participants in the intermediate BMI group (n = 2,274). Volume differences were observed in the frontal, parietal, temporal, and cingulate cortices, as well as the hippocampal gyrus; amygdala; superior, middle, and inferior temporal gyri; temporal pole; parahippocampal gyrus; and cuneus. Compared with the intermediate BMI group, the low BMI group (n = 219) presented a significantly lower volume in the middle temporal gyrus (1.91% vs. 1.95%, p = 0.008). These findings indicate that older adults with frailty experience differences in brain volume, with atrophy patterns differing based on BMI. Therefore, the central nervous system dysfunction may play a role in the mechanisms underlying frailty.

Keywords: Brain volume; Community-dwelling; Frailty; Obesity; Older adult; Underweight.

Fig. 1

Process for selecting participants for this study. Eligible participants were recruited, stratified by body mass index, and subjected to frailty and brain volume analyses. *Participants with insufficient data quality for FreeSurfer analysis, including 17 individuals in whom an error occurred during the automated analysis process, 29 with extreme outliers in the estimated total intracranial volume, and 122 with extreme outliers in the volumes of at least five brain regions. BMI, body mass index; JPSC-AD, Japan Prospective Studies Collaboration for Aging and Dementia; n, number; T1WI, T1-weighted image.

Fig. 2

Estimated odds ratios of frailty: comparison of the low and high body mass index (BMI) groups with the reference group (intermediate BMI) in 7,783 participants eligible for frailty analysis. BMI, body mass index. The values are odds ratios (95% CIs, p values). *Adjusted for age, sex, institution, ≤ 9 years of formal education, hypertension, diabetes mellitus, history of cerebrovascular disease, and history of heart disease.

Fig. 3

Brain volume differences in 3,627 older adults living with frailty stratified by body mass index (BMI). The color intensity on the heatmap indicates the magnitude of the p value, i.e., the level of statistical significance. Significant differences in volume were apparent between the older adults living with frailty in the low and high BMI groups and those in the intermediate BMI group. BMI body mass index, H high, L lower, N normal, vs. versus.