Body mass index and regional brain N-acetylaspartate: a systematic review and meta-analysis of ¹H-MRS studies

Obesity has increasingly been associated with structural brain alterations and cognitive dysfunction; however, the neurometabolic correlates of these findings remain unclear. Proton magnetic resonance spectroscopy (¹H-MRS) provides a non-invasive method for examining neurometabolites in vivo, including N-acetylaspartate (NAA), a marker commonly associated with neuronal integrity and mitochondrial metabolism. The present study systematically reviewed and quantitatively synthesized existing ¹H-MRS literature examining the relationship between body mass index (BMI) and regional brain NAA concentrations.

Following PRISMA guidelines, systematic searches of PubMed, Scopus, and Embase identified 23 eligible studies. Separate regional random-effects meta-analyses were conducted for categorical comparisons between groups with normal weight and groups with overweight or obesity, and for continuous associations between BMI and NAA. Supplementary pooled analyses were conducted across brain regions to quantify an overall brain-wide assessment.

Higher BMI was associated with lower NAA concentrations within the frontal region across both categorical (Hedges' g = -0.48, 95% CI [-0.93, -0.03], p = 0.035) and continuous analyses (r = -0.218, 95% CI [-0.323, -0.108], p < 0.001). Additional significant associations were observed in the right hippocampal region in the categorical analysis (Hedges' g = -0.51, 95% CI [-0.84, -0.19], p = 0.002) and the parietal region in the continuous analysis (r = -0.256, 95% CI [-0.463, -0.022], p = 0.032). Pooling results across all regions demonstrated consistently significant negative BMI-NAA associations across continuous analyses of both the lower-bound (most negative) and upper-bound (least negative/most positive) models, while categorical pooled analyses retained significance only within the lower-bound model.

In this meta-analysis, higher BMI was associated with lower neural NAA, most consistently in the frontal regions, but with pooled analyses suggesting more widespread NAA-obesity associations. Findings support the utility of ¹H-MRS as a complementary neuroimaging modality within obesity-related brain research.