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Clin Interv Aging. 2014 Oct 23;9:1823-9. doi: 10.2147/CIA.S64766. eCollection 2014.

The relationship between cholesterol and cognitive function is homocysteine-dependent.

Author information

Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA ; Eli Lilly and Company, Indianapolis, Indiana, USA.
Shandong Institute for Prevention and Treatment of Endemic Disease in China, Jinan, People's Republic of China.
Sichuan Provincial Center for Disease Control and Prevention in China, Chengdu, People's Republic of China.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA ; Indiana University Center for Aging Research, Indianapolis, Indiana, USA ; Regenstrief Institute, Inc., Indianapolis, Indiana, USA.



Previous studies have identified hyperlipidemia as a potential risk factor for dementia and Alzheimer's disease. However, studies on cholesterol measured in late-life and cognitive function have been inconsistent. Few studies have explored nonlinear relationships or considered interactions with other biomarker measures.


A cross-sectional sample of 1,889 participants from four rural counties in the People's Republic of China was included in this analysis. Serum total cholesterol, high-density lipoprotein, triglycerides, and homocysteine levels were measured in fasting blood samples. A composite cognitive score was derived based on nine standardized cognitive test scores. Analysis of covariance models were used to investigate the association between biomarker measures and the composite cognitive scores.


There was a significant interaction between the homocysteine quartile group and the cholesterol quartile group on cognitive scores (P=0.0478). In participants with normal homocysteine levels, an inverse U-shaped relationship between total cholesterol level and cognitive score was found, indicating that both low and high cholesterol levels were associated with lower cognitive scores. In participants with high homocysteine levels, no significant association between cholesterol and cognition was found.


The relationship between cholesterol levels and cognitive function depends upon homocysteine levels, suggesting an interactive role between cholesterol and homocysteine on cognitive function in the elderly population. Additional research is required to confirm our findings in other populations, and to explore potential mechanisms underlying the lipid-homocysteine interaction.


cholesterol; cognitive function; homocysteine

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