Higher Coffee Consumption Is Associated With Reduced Cerebral Gray Matter Volume: A Mendelian Randomization Study

Abstract

BackgroundRecently published two-sample Mendelian randomization (MR) studies showed that genetically predicted coffee consumption may be associated with increased risk of Alzheimer’s disease and intracerebral hemorrhage but associated with a decreased risk of small vessel ischemic stroke. We aimed to investigate the effects of genetically predicted coffee consumption on magnetic resonance imaging (MRI) markers of cerebral small vessel disease and brain volume using the two-sample MR method.MethodsTwelve single nucleotide polymorphisms (SNPs) in up to 375,833 individuals were used as genetic instruments for cups consumed per day of coffee. Another four SNPs from an independent sample were used to perform the replication analysis. Three SNPs in up to 45,821 individuals were used as genetic instruments for high coffee consumption vs. low/no coffee consumption.ResultsMendelian randomization analysis showed that coffee consumption (cups/day) was inversely associated with gray matter volume (beta = −0.371, 95% CI = −0.596 to −0.147, p = 0.001). Replication analysis and multivariable analyses after adjusting for other risk factors confirmed the effect. High coffee consumption was also suggestively associated with decreased gray matter volume (beta = −0.061, 95% CI = −0.109 to −0.013, p = 0.013) compared with low/no coffee consumption. All analyses did not find an effect of coffee consumption on other outcomes including white matter hyperintensity volume, mean diffusivity, fractional anisotropy, brain microbleed, total brain volume, white matter volume, and hippocampus volume.ConclusionThis two-sample MR study showed that genetically predicted higher coffee consumption is causally associated with reduced gray matter volume of the brain.

Association of coffee consumption and striatal volume in patients with Parkinson's disease and healthy controls

“…In the present study, we observed an inverse association between current coffee consumption and striatal volume in controls and between coffee cups consumed per day and striatal volume in current consumers of PD and controls. Recently, using the data from UK Biobank, several large‐scale studies revealed an inverse association between coffee consumption and gray matter volume 17,18 . Moreover, the finding of this inverse association was supported by a double‐blind randomized controlled trial (RCT) 35 .…”

“…Recently, using the data from UK Biobank, several large-scale studies revealed an inverse association between coffee consumption and gray matter volume. 17,18 Moreover, the finding of this inverse association was supported by a double-blind randomized controlled trial (RCT). 35 A total of 20 healthy male habitual caffeine consumers were recruited for the RCT study.…”

“…On the one hand, several studies demonstrated that chronic coffee consumption was associated with decreased functional connectivity 15 and decreased metabolism 16 . On the other hand, several recent studies revealed an inverse association between coffee consumption and brain volume using the data from UK Biobank 17,18 . PD is characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway 19 .…”

“… 16 On the other hand, several recent studies revealed an inverse association between coffee consumption and brain volume using the data from UK Biobank. 17 , 18 PD is characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. 19 However, there have been few investigations about whether chronic coffee consumption is associated with the change in striatal volume.…”

Extra cup of tea intake associated with increased risk of Alzheimer’s disease: Genetic insights from Mendelian randomization

“…Other studies have found that diet or eating behaviors could impact brain volumes ( 43 – 45 ). For example, a recent Mendelian randomization study found inverse association between coffee consumption and gray matter volume ( 46 ). It has been suggested that a larger brain volume provides a greater cerebral reserve against the effects of AD, maintaining cognitive function in the presence of neurodegeneration ( 47 ).…”