Frontal White Matter Hyperintensities and Executive Functioning Performance in Older Adults

Area of Science:

• Neuroscience
• Gerontology
• Radiology

Background:

• Frontal lobe structures and executive functions decline with age.
• Frontal lobe white matter hyperintensities (WMH) effects on executive function in normal aging are understudied.
• Executive functions include working memory, set-shifting, and inhibitory control.

Purpose of the Study:

• To assess the relationship between region-specific frontal WMH load and executive function in healthy older adults.
• To investigate the impact of WMH on working memory, set-shifting, and inhibitory control.
• To understand the role of WMH in age-related cognitive decline.

Main Methods:

• 279 healthy older adults (65-88 years) completed NIH Toolbox Cognition Battery tasks.
• 3T T1-weighted and FLAIR MRI scans were acquired.
• Lesion Segmentation Toolbox and FreeSurfer 6.0 quantified WMH and defined frontal lobe regions of interest (ROIs).
• Linear regressions analyzed associations between WMH load and cognitive performance, controlling for covariates.

Main Results:

• Greater WMH load in bilateral superior frontal and right medial orbitofrontal ROIs was associated with poorer set-shifting performance.
• Higher WMH load in the right superior frontal ROI correlated with poorer inhibitory control.
• No significant associations were found between frontal WMH and working memory performance.

Conclusions:

• Frontal lobe WMH location and pattern are important for understanding age-related declines in set-shifting and inhibition.
• WMH may selectively contribute to executive function decline in aging.
• Findings highlight the potential role of WMH in the cognitive aging profile, independent of age and cardiovascular risk.