Functional brain network connectivity patterns associated with midlife metabolic syndrome and cognitive...

Metabolic syndrome (MetS) may amplify neural vulnerability via vascular and inflammatory pathways. Existing literature suggests there are alterations to functional brain network organization in adults with MetS, though the specific patterns and their relation to cognitive vulnerabilities warrant further investigation, particularly in a midlife sample.

Cognitively unimpaired, community-dwelling adults (N = 223; ages 40-65; MetS = 73) were included. Resting-state fMRI data were preprocessed with fMRIPrep and analyzed using the Schaefer 400-parcel atlas. Functional connectivity (FC) metrics included within- and between-network connectivity, system segregation, modularity, and global efficiency. Cognitive performance was measured via neuropsychological tests for memory and executive functioning. Generalized linear models (adjusted for age, sex, framewise displacement) were used to examine group differences in FC metrics and associations between FC metrics and cognitive performance.

MetS participants showed reduced within-network connectivity in the default mode network (DMN; adjusted p = 0.038, partial η ² = 0.035). Follow-up component-level analyses indicated abdominal obesity and low HDL cholesterol were associated with reduced connectivity in DMN (abdominal obesity: adjusted p = 0.027, partial η ² = 0.029; cholesterol: adjusted p = 0.002, partial η ² = 0.058). Reduced DMN connectivity was associated with poorer verbal fluency (adjusted p = 0.026, partial R ² = 0.037). Exploratory analyses identified age and sex as factors that interacted with MetS group to influence FC metrics (p's < 0.050, partial η ²'s = 0.020-0.030).

Midlife MetS was associated with modest reductions in within-network DMN connectivity, with abdominal obesity and low HDL cholesterol as the primary contributing MetS components. Reduced DMN connectivity was associated with poorer verbal fluency performance. These findings suggest that subtle differences in higher-order functional brain network organization associated with metabolic syndrome can be detected during midlife and are related to cognitive functioning, highlighting the importance of prevention and intervention of cardiometabolic risk in midlife to preserve network integrity and cognitive health.