Plasma lipids are associated with white matter microstructural changes and axonal degeneration

Area of Science:

• Neuroscience
• Cardiovascular Research
• Aging Research

Background:

• Dyslipidemia is a known risk factor for cognitive impairment.
• Interindividual variability in plasma lipids may influence brain health.
• White matter microstructure and axonal integrity are crucial for cognitive function.

Purpose of the Study:

• To investigate the association between plasma lipid levels and white matter microstructure in healthy adults.
• To explore the relationship between plasma lipids and cerebrospinal fluid neurofilament light chain (NfL), a marker of axonal degeneration.
• To examine the moderating effect of lipids on the NfL-white matter relationship.

Main Methods:

• Diffusion tensor imaging (DTI) was used to assess white matter microstructure in 273 healthy adults.
• Seven regions of interest within cognitive neurocircuitry were analyzed.
• Plasma lipid levels (LDL, HDL, TG) and CSF NfL were measured.

Main Results:

• Lower levels of low-density lipoprotein (LDL) and triglycerides (TG) were associated with reduced axial diffusivity (AxD) in multiple white matter regions.
• Higher levels of high-density lipoproteins (HDL) correlated with increased AxD.
• LDL and TG levels moderated the relationship between NfL and AxD in specific white matter tracts, independent of APOE genotype, blood pressure, or statin use.

Conclusions:

• Plasma lipid levels are significantly associated with white matter microstructural integrity and axonal degeneration.
• Lipid profiles may represent a modifiable risk factor in the progression from healthy aging to cognitive impairment.
• These findings highlight the importance of managing dyslipidemia for brain health in aging individuals.