Association of coffee and genetic risk with incident dementia in middle-aged and elderly adults

Background:: Prior evidence suggests that coffee might be related to dementia, however, little is known about coffee and dementia in individuals with elevated genetic susceptibility for dementia. Additionally, most previous studies have focused on total coffee instead of examining coffee types separately. Methods: This study included 203,776 participants (60-73 years old) from the UK Biobank who were initially free of dementia. Polygenic risk scores for dementia were divided into quintile to stratify individuals into low (lowest quintile), intermediate (quintile 2-4), and high (highest quintile) genetic risk categories. Coffee intake was assessed at baseline and included total, instant, ground, and decaffeinated coffee. Results: During a median follow-up of 11.4 years, 4405 cases of dementia occurred (1856 Alzheimer's disease [AD], 1105 vascular dementia). Compared to non-coffee drinking, heavy instant coffee drinking (> 6 cups/day) and moderate decaffeinated coffee drinking (1-3 cups/day) were associated with a higher risk of dementia (hazard ratio [HR] 1.19-1.34) and AD (HR 1.41-1.51), while moderate ground coffee drinking was associated with a lower risk of dementia (HR, 0.78; P = 0 .001) and vascular dementia (HR, 0.58; P < 0.001). Among participants at high genetic risk, heavy coffee drinking was associated with a 95% (HR; 1.95, 95% CI, 1.21-3.16) higher risk of AD than non-coffee drinking. We found an interaction between coffee and genetic risk in relation to AD (P = 0 .038). Conclusion: The association of dementia and coffee varied by coffee types. Heavy coffee consumption was associated with a higher risk of AD in individuals with high genetic risk for dementia.