CAPE TOWN - MRI shows that insulin resistance rather than chronic high blood sugar is the primary driver of cerebral metabolic stress and functional decline in older adults, researchers have reported.
Results from a study presented May 14 at the International Society of Magnetic Resonance in Medicine (ISMRM) meeting offer neuroimaging evidence to explain why Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) outperforms HbA1c as a clinical predictor of cognitive and daily functioning.
It also "establishes MRI-quantified OEF [oxygen extraction fraction] as a new, quantifiable target for therapies aimed at preserving brain function in older adults," wrote presenter Salil Soman, MD, of the University of California in San Francisco, and colleagues.
Predicting functional decline in older adults can be tricky, and traditional metabolic markers such as HbAIc are "suboptimal," the group explained. Functional decline tends to be measured by a person's ability to perform "instrumental activities of daily living" (IADL) -- tasks that rely on brain regions that perform executive function (left caudal middle frontal cortex) and visuospatial processing (right cuneus).
"Accurate, noninvasive predictors of IADL decline are lacking," the team wrote. "We hypothesized that the HOMA-IR is a superior predictor to HbA1c, [and] propose a neurobiological mechanism where insulin resistance induces cerebrovascular dysfunction, leading to increased brain metabolic stress, measured by MRI-quantified OEF, in these critical regions, ultimately causing IADL deterioration."
Soman and colleagues conducted a study that included 246 adults ages 45 to 75 years who participated in the Boston Puerto Rican Health Study and who had complete metabolic, functional, and MRI exam data. Using the MRI data, the researchers quantified OEF, which measures the balance between cerebral oxygen supply and demand, to determine levels of metabolic stress in the left caudal middle frontal cortex and right cuneus.
They reported the following:
- HOMA-IR showed associations with increased OEF in both the left caudal middle frontal cortex (p < 0.05) and right cuneus (p < 0.05). But HbA1c showed no significant association with OEF in these regions (p > 0.05).
- HOMA-IR was a significant predictor of worse functional category (p < 0.05), whereas HbA1c was not (p > 0.05), a finding confirmed when both markers were included in a joint model adjusting for age. Only HOMA-IR remained a significant predictor while HbA1c lost all significance.
- HOMA-IR achieved an odds ratio of 1.08, indicating an 8% increased odds of being in a worse IADL category per unit increase.
The study results underscore MRI's value in identifying and tracking patients at risk of functional decline, and show promise for "using HOMA-IR as an early biomarker and position regional OEF as a potential intermediate biomarker for future therapeutic trials," the researchers noted.
"Our findings demonstrate that HOMA-IR is a more robust predictor of functional decline than HbA1c in this cohort of older Puerto Rican adults, a population with a high burden of metabolic disease," they concluded. "Crucially, this clinical superiority is mechanistically supported by our novel MRI findings, which establish a direct link between systemic insulin resistance and metabolic stress in brain networks essential for daily function."
Check out AuntMinnie’s full coverage of ISMRM 2026 on our ShowCast.
