Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants

Abstract

Coffee’s long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (β = −0.0007, 95% C.I. −0.009 to 0.008, P = 0.87; β = −0.001, 95% C.I. −0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (Pheterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

Association of Coffee, Decaffeinated Coffee and Caffeine Intake from Coffee with Cognitive Performance in Older Adults: National Health and Nutrition Examination Survey (NHANES) 2011–2014.

“…In a large, population-based study of 9003 British people, Jarvis [53] found a significant positive trend between coffee intake and cognitive performance. Furthermore, studies of the association between coffee and cognitive performance also indicated that although reduced risk was related to coffee consumption in men [51], the effect was more pronounced in women [19,20], whereas some studies [54][55][56][57] showed null or adverse associations. A population-based Rotterdam study [55] of 2914 participants in a five-year follow-up, and a cohort study of 14,563 participants (35-74 years old) conducted by Araújo [56], showed null or adverse effects of coffee consumption on cognitive performance.…”

Mendelian Randomization Studies of Coffee and Caffeine Consumption

“…When individual-level data are available, a common strategy is to restrict SNP-outcome analysis to coffee drinkers arguing that the SNPs are associated with coffee drinking (heaviness) and thus causal relationships should only be observed among coffee drinkers (a form of gene-environment interaction) [ 43 , 44 , 48 , 49 , 56 , 59 , 66 ]. SNP-outcome associations among non-drinkers (‘negative control sample’) would suggest a violation in at least one of the assumptions [ 59 , 66 ].…”

Role of phytochemicals as nutraceuticals for cognitive functions affected in ageing

“…‐Mendelian randomisation study (>300,000 coffee drinkers) concluded no evidence that coffee intake could beneficially affect global cognition or memory (Zhou et al, )…”

“…Its antioxidant mechanisms explain its ability to improve memory in many of these studies, including via reduced oxidative damage through enhancing glutathione (GSH) and decreasing lipid peroxide levels in brain tissue Sarker & Franks, 2018;Williams et al, 2011). Animal studies also show curcumin improves memory tasks and it can reverse stress-induced reductions in neurogenesis, associated with brain-derived neurotrophic factor (BDNF; Poulose, Miller, Scott, & Shukitt-Hale, T A B L E 1 Nutraceutical phytochemicals with relevance to cognition in normal and pathological brain ageing EGCG -Antioxidant and neuroprotective against oxidative stress via elevation of mRNA expression of γ-glutamylcysteine ligase to increase cellular GSH, stimulation of PKC and modulation of cell cycle genes (Williams et al, 2011) -Activates α7 nicotinic receptors and signalling molecules P13K and AKT to suppress Bcl-2 down-regulation (Howes & Simmonds, 2014) -Inhibits AChE, is anti-inflammatory via different mechanisms and inhibits neuroinflammatory response of microglia to Aβ (Cascella et al, 2017) -Inhibits βand γ-secretase activities (Costa et al, 2017;Williams et al, 2011) Epicatechin -Increases GSH levels in astrocytes -Improves memory by ameliorating lipid peroxidation and ROS in rats with Aβ-induced hippocampal toxicity (Williams et al, 2011) Cocoa flavanols -Enhance expression of neuroprotective and neuromodulatory proteins (Sokolov et al, 2013) -Improve angiogenesis and cerebral blood flow in the brain (Dominguez & Barbagallo, 2018) Green tea -Epidemiological evidence suggests regular intake reduced age-related cognitive decline and dementia risk (Williams et al, 2011) -Intake (2 g daily for 3 months in an RCT) improved cognitive performance ( affect global cognition or memory (Zhou et al, 2018) Caffeoylquinic acids (including chlorogenic acid)…”