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

Abstract

BackgroundObservational studies report inconclusive effects of tea consumption on the risk of Alzheimer’s disease (AD), and the mechanisms are unclear. This study aims to investigate the effects of genetically predicted tea intake (cups of tea consumed per day) on AD, brain volume, and cerebral small vessel disease (CSVD) using the two-sample Mendelian randomization (MR) method.MethodsSummary statistics of tea intake were obtained from UK Biobank (N = 447,485), and AD was from the International Genomics of Alzheimer’s Project (N = 54,162). Genetic instruments were retrieved from UK Biobank using brain imaging-derived phenotypes for brain volume outcomes (N > 33,224) and genome-wide association studies for CSVD (N: 17,663–48,454).ResultsIn the primary MR analysis, tea intake significantly increased the risk of AD using two different methods (ORIVW = 1.48, 95% CI: [1.14, 1.93]; ORWM = 2.00, 95% CI: [1.26, 3.18]) and reached a weak significant level using MR-Egger regression (p < 0.1). The result passed all the sensitivity analyses, including heterogeneity, pleiotropy, and outlier tests. In the secondary MR analysis, per extra cup of tea significantly decreased gray matter (βWM = −1.63, 95% CI: [−2.41, −0.85]) and right hippocampus volume (βWM = −1.78, 95% CI: [−2.76, −0.79]). We found a nonlinear association between tea intake and AD in association analysis, which suggested that over-drinking with more than 13 cups per day might be a risk factor for AD. Association analysis results were consistent with MR results.ConclusionThis study revealed a potential causal association between per extra cup of tea and an increased risk of AD. Genetically predicted tea intake was associated with a decreased brain volume of gray matter and the right hippocampus, which indicates that over-drinking tea might lead to a decline in language and memory functions. Our results shed light on a novel possible mechanism of tea intake to increase the risk of AD by reducing brain volume.

Genetically determined dietary habits and risk of Alzheimer’s disease: a Mendelian randomization study

“…Moreover, a meta-analysis of prospective studies revealed that the tea could be inversely associated with neurodegenerative disorders ( 43 ), which was also consistent with our results. Conversely, a MR study genetically suggested a potential causal link between increased tea intake and elevated AD risk, with genetically predicted tea intake associated with decreased brain volume, particularly in the gray matter and right hippocampus ( 44 ). Finally, a dose–response meta-analysis indicated an inverse association between tea consumption and cognitive disorders, suggesting 1 cup/day of tea intake leads to an 11% reduction in cognitive deficits ( 45 ).…”

Association of biological age with health outcomes and its modifiable factors

“…In addition, most previous studies suggested that tea had protective effects on aging (Feng et al, 2021 ; Zhang et al, 2021 ). However, some studies have found that excess tea intake has an adverse impact on cognition and is associated with Alzheimer's disease (Hu et al, 2022 ; Sun et al, 2023 ).…”

Trends and hotspots in tea and Alzheimer's disease research from 2014 to 2023: A bibliometric and visual analysis

“…Tea stands out as a ubiquitous beverage that has garnered substantial attention due to its potential health-enhancing properties [ 13 ]. Rich in caffeine and tea polyphenols [ 14 ], the advantageous attributes of tea are primarily ascribed to its robust polyphenol content, particularly catechin, renowned for its potent antioxidant capabilities [ 14 ].…”

“…Regardless of its variety, tea and its derivatives exhibit a spectrum of effects, including antibacterial qualities [ 15 ], anti-inflammatory attributes [ 16 ], antitumor potential [ 17 ], antiviral properties [ 18 ], and more. The documented ability of catechin's polyphenols to impede amyloid-beta aggregation and exhibit anti-apoptotic effects suggests a potentially substantial protective role against AD [ 13 , 14 ]. The presence of theanine in tea appears to correlate with improvements in cognitive function [ 19 , 20 ].…”