The Role of Brain Structure in Explaining Physical Functioning in Male Veterans With Impaired Kidney Function

Area of Science:

• Nephrology
• Neurology
• Geriatrics
• Cardiology

Background:

• Older adults with chronic kidney disease (CKD) exhibit higher rates of physical function and cardiorespiratory fitness deficits.
• Emerging evidence suggests covert brain pathology may underlie these functional impairments, but previous studies often failed to control for cardiac comorbidities.
• This study investigates brain structure, physical performance, and cardiorespiratory fitness in older adults with CKD versus hypertensive controls, exploring brain structure's mediating role.

Purpose of the Study:

• To compare global brain structure, physical performance, and cardiorespiratory fitness between older adults with CKD and hypertensive controls.
• To examine the mediating role of brain structure in the relationship between renal function and physical function.
• To control for common cardiac comorbidities in the analysis.

Main Methods:

• Recruited older male veterans with CKD and hypertensive controls.
• Assessed physical function using Six Minute Walk Test (6MWT), Short Physical Performance Battery, and Timed Up and Go.
• Evaluated cardiorespiratory fitness via graded exercise treadmill test and quantified brain structure (gray matter, white matter, white matter lesions) using MRI.

Main Results:

• Older adults with CKD demonstrated lower gray matter volume, poorer endurance (6MWT), and reduced cardiorespiratory fitness (VO2 peak) compared to controls.
• Global gray matter volume significantly mediated the relationship between renal function and physical function measures.
• This mediation effect persisted even after accounting for cardiac comorbidities and risk factors.

Conclusions:

• CKD is associated with distinct pathways, beyond traditional hemodynamic or ischemic mechanisms, that contribute to impaired physical functioning.
• Gray matter volume is a key factor linking impaired kidney function to reduced physical performance in older adults.
• These findings highlight the importance of considering brain health in managing CKD patients.