Cholesterol and Vascular Risk Factors in Cognitive Decline

Cholesterol, a lipid essential for neuronal membrane integrity and synaptic function, plays a dual role in cognitive health. Low-density lipoprotein cholesterol (LDL-C) contributes to atherosclerotic plaque formation in cerebral vessels, while high-density lipoprotein cholesterol (HDL-C) promotes cholesterol efflux and may protect against vascular injury. Dysregulated lipid metabolism is implicated in amyloid β aggregation, tau hyperphosphorylation and blood–brain barrier dysfunction, all of which underpin Alzheimer’s disease pathology. Vascular risk factors such as hypertension, diabetes and obesity exacerbate endothelial damage, cerebral small vessel disease and white matter lesions, accelerating cognitive decline. Longitudinal and cross-sectional studies reveal that elevated LDL-C and triglycerides correlate with faster neurodegeneration, whereas higher HDL-C shows complex associations with both protective and detrimental outcomes depending on age and vascular comorbidity. Interventions targeting modifiable risks—through diet, exercise, antihypertensive and lipid-lowering therapies—hold promise for delaying onset and progression of dementia. A nuanced understanding of lipid fractions in vascular and neurodegenerative pathways is therefore critical to develop personalised prevention strategies across diverse populations.

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Cholesterol and Vascular Risk Factors in Cognitive Decline publication trend

The graph below shows the total number of articles in cholesterol and vascular risk factors in cognitive decline across all publications each year (not limited to Nature Index journals).

Technical terms

Low-density lipoprotein cholesterol (LDL-C): The fraction of cholesterol that transports lipids to peripheral tissues and can accumulate in arterial walls.

High-density lipoprotein cholesterol (HDL-C): The lipoprotein fraction that mediates reverse cholesterol transport from tissues to the liver.

Blood–brain barrier: The endothelial interface regulating exchange between the bloodstream and the central nervous system.

Cerebral small vessel disease (CSVD): Pathological changes in small brain vessels that manifest as white matter hyperintensities and lacunar infarcts.

Mendelian randomisation: A genetic epidemiological method that uses genetic variants as proxies to infer causal relationships between risk factors and outcomes.

References

1. Associations between lipid profiles and late‐life cognitive impairment among oldest‐old and centenarian adults. MedComm (2023).
2. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease. JAMA Network Open (2023).
3. Distinct effects of cholesterol profile components on amyloid and vascular burdens. Alzheimer's Research & Therapy (2023).