An insight into impact of lipid metabolism on cognitive impairment

Cognitive impairment (CI) is a mental disorder affecting cognition and understanding, predominantly classified into mild CI and senile dementia. The disease is associated with various factors, including chronic brain injuries, aging, systemic diseases, mental health, and psychological influences. Although the exact pathological mechanisms behind CI are not fully understood, it is often linked with underlying conditions like diabetes and hyperlipidemia. Research indicates that various lipid metabolism markers in the body, such as total cholesterol, HDL, LDL, triglycerides, and apolipoproteins, are closely linked to CI. Hyperlipidemia is identified as a significant risk factor in the development of CI, yet the precise relationship between dyslipidemia and CI remains unclear. Additionally, the effectiveness of lipid-lowering medications for preventing and treating CI has not been verified. The current study aimed to review recent findings on how lipid metabolism disorders influence CI, with the goal of exploring how managing blood lipid levels may aid in the prevention and treatment of CI, thereby offering insights for clinical management.

Cholesterol is abundant in the brain and other tissues, and high blood cholesterol levels can lead to lipid plaques, impairing blood flow and causing tissue ischemia and damage.

Total Cholesterol (TC) and CI

Elevated TC is a major contributor to CI. Key mechanisms include:

• Cerebral Blood Flow: High TC can disrupt blood supply and promote plaque formation in arteries, increasing the risk of ischemia.
• Blood-Brain Barrier (BBB) Damage: Elevated TC levels can harm the BBB, allowing harmful substances to penetrate and contribute to CI.
• Oxidative Stress: High TC induces oxidative stress, damaging neuronal membranes.

Managing TC levels is recommended to mitigate CI risk.

High-Density Lipoprotein Cholesterol (HDL-C) and CI

HDL-C helps transport cholesterol to the liver, with low HDL-C levels linked to CI severity. HDL-C protects against CI by:

• Inhibiting Plaque Formation: It prevents lipid buildup in arteries, maintaining blood flow.
• Reducing Atherosclerosis: HDL-C regulates blood flow and decreases CI risk.
• Antithrombotic Effects: It helps prevent clot formation, protecting cognitive functions.

Monitoring HDL-C is important for CI prevention.

Low-Density Lipoprotein Cholesterol (LDL-C) and CI

Increased LDL-C levels are associated with CI risk through:

• Chronic Inflammation: High LDL-C can lead to atherosclerosis and cerebral microvascular injury.
• Lipid Peroxide Accumulation: Elevated LDL-C worsens blood viscosity, increasing CI risk.

Lowering LDL-C may be an effective strategy to prevent CI.

Triglycerides (TG) and CI

The role of TG in CI is debated. High TG levels may damage the BBB and correlate with inflammation, possibly contributing to cognitive decline. However, some studies find no significant link between TG and memory.

Apolipoproteins (Apo) and CI

Apolipoproteins (Apo A, Apo B, and Apo E) are critical in lipid metabolism and CI:

• Apo A: Protects against CI by promoting cholesterol clearance.
• Apo B: High levels are linked to increased CI risk.
• Apo E: Affects cholesterol transport and Aβ metabolism, with certain genetic variants increasing CI risk.

Lipoprotein(a) [Lp(a)] is also associated with elevated CI risk due to its role in inflammation and blood flow.

To summarize, various forms of cholesterol significantly influence cognitive impairment, highlighting the need for effective lipid management for cognitive health.

Source: Zhang M, Zhu YH, Zhu ZQ. Research advances in the influence of lipid metabolism on cognitive impairment. Ibrain. 2022 Feb 18;10(1):83-92. doi: 10.1002/ibra.12018. PMID: 38682015; PMCID: PMC11045198.