Study Explores Impact of LDL Levels on Alzheimer, Dementia Risk

Low levels of low-density lipoprotein (LDL) cholesterol due to genetic variant is not associated with and increased risk of dementia or Parkinson disease, but may be associated with reduced risk of developing Alzheimer disease, according to a recent study.

The researchers included 111,194 individuals from the Danish general population in their Mendelian randomization study. Of these participants, 4087 (3.7%) had LDL cholesterol levels of less than 1.8 mmol/L, 22,335 (18%) had levels of 1.8-2.59 mmol/L, 57,847 (52%) had levels of 2.6-3.99 mmol/l, and 28,925 (26%) had levels of 4.0 mmol/L or higher.
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During follow-up, 1001 participants developed Alzheimer disease, 256 developed vascular dementia, 2154 developed any dementia, and 460 developed Parkinson disease.

Overall, multifactorially adjusted hazard ratio for Parkinson disease in participants with LDL cholesterol levels of less than 1.8 mmol/L vs 4.0 mmol/L or greater was 1.70. However, the hazard ratios for Alzheimer disease, vascular dementia, or any dementia did not differ from 1.0.

PCSK9 and HMGCR variants were associated with a combined 9.3% lower LDL cholesterol level, and the risk ratios for a lifelong 1 mmol/L lower LDL cholesterol level were 0.57 for Alzheimer’s disease, 0.81 for vascular dementia, 0.66 for any dementia, and 1.02 for Parkinson’s disease.

However, data from 280 genetic variants from the International Genomics of Alzheimer’s Project suggested a causal relationship between low LDL cholesterol levels and reduced risk of Alzheimer disease.

“Low LDL cholesterol levels due to PCSK9 and HMGCR genetic variants did not appear to increase the risk of Alzheimer disease, vascular dementia, any dementia, or Parkinson disease. However, using similar data on 380 genetic variants associated with low LDL cholesterol levels, genetically low LDL cholesterol was associated with a reduced risk, suggesting a causal effect of low LDL cholesterol level in reducing the risk of Alzheimer disease,” the researchers concluded.

—Michael Potts

Reference:

Benn M, Nordestgaard BG, Frikke-Schmidt R, Tybjaerg-Hansen A. Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer’s disease and Parkinson’s disease: Mendelian randomisation study [published online April 24, 2017]. BMJ. doi: https://doi.org/10.1136/bmj.j1648.