Differential associations between systemic markers of disease and white matter tissue health in middle-aged and older adults

Age-associated cerebrovascular disease impacts brain tissue integrity, but other factors, including normal variation in blood markers of systemic health, may also influence the structural integrity of the brain. This cross-sectional study included 139 individuals between 40 to 86 years old who were physically healthy and cognitively intact. Eleven markers (total-cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceride, insulin, fasting glucose, glycated hemoglobin, creatinine, blood urea nitrogen, albumin, total protein) and five derived indicators (estimated glomerular filtration rate, creatinine clearance rate, insulin-resistance, average glucose, and cholesterol/high-density lipoprotein ratio) were obtained from blood sampling. Diffusion tensor imaging was used to evaluate white matter tissue health. Blood markers were clustered into five factors. The first factor (defined as insulin/high-density lipoprotein factor) was associated with markers of integrity in the deep white matter and projection fiber systems, while the third factor (defined as kidney function factor) was associated with different markers of integrity in the periventricular and watershed white matter regions. Differential segregated associations for insulin and high-density lipoprotein levels and serum markers of kidney function may provide information about distinct mechanisms of brain changes across the lifespan. These results emphasize the need to determine whether therapeutic modulation of systemic health and organ function may prevent decline in brain structural integrity.