Interactions between aging and white matter hyperintensities-defined cerebral small vessel disease on prefrontal...

Metabolic disruption in the prefrontal cortex is closely associated with functional decline in cerebral small vessel disease (CSVD), especially among older adults. This study aimed to investigate both the separate and combined effects of aging and CSVD on prefrontal cortex metabolism. A total of 191 participants who underwent ¹⁸F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging scanning were divided into four groups: middle-aged healthy control (HC) (n = 60), middle-aged CSVD patients (n = 52), older HC (n = 35) and older CSVD patients (n = 44). Age was categorized as middle-aged (40-59  years) and older (60-80  years), and enrolled CSVD cases were strictly diagnosed as white matter hyperintensities (WMH)-defined CSVD following standardized criteria. Main and interaction effects of aging and CSVD on prefrontal cortex metabolism were analyzed across three levels: local region, connectivity, and network, with multiple comparison correction applied. Significant interactions between aging and CSVD were identified in the relative mean standardized uptake value of the prefrontal cortex, as well as in global (clustering coefficient) and nodal properties (nodal clustering coefficient, nodal efficiency, and nodal local efficiency). Additionally, significant main effects of age and CSVD were observed on the prefrontal cortex' average standardized uptake value, whereas main effects of age were found on both global and nodal properties of the prefrontal metabolic network. These findings demonstrate altered prefrontal metabolic profiles associated with aging and WMH-defined CSVD. These observed metabolic patterns offer preliminary insights, and may guide future studies integrating comprehensive clinical assessments and longitudinal follow-up.