Associations Of Coffee Consumption And Cerebrospinal Fluid Biomarkers Of Alzheimer’s Disease Pathology

Objective: Healthy lifestyles and scientific and reasonable dietary intake are closely related to Alzheimer’s disease(AD)and cognitive impairment.Substantial epidemiological evidence suggests that appropriate lifestyle modifications can delay the onset of AD and reduce the risk of dementia.Many studies have shown that adherence to healthy eating patterns is related to better cognitive function,so healthy and reasonable eating habits may play an important role in preventing cognitive decline and dementia.At present,some preclinical and epidemiological studies have shown that coffee consumption has a protective effect on AD and cognitive impairment.In this study,based on a large number of healthy middle-aged and elderly people with normal cognition and no other neurological diseases,we studied the relationship between coffee consumption and cerebrospinal fluid biomarkers of AD,and determined whether these relationships were different in a specific population background.Methods: This study identified a total of 1035 participants from the Chinese Alzheimer’s Biomarker and Lifesty LE(CABLE)study database.All the participants were aged between 40 and 90 years old and had normal cognition and no other neurological diseases.All participants underwent clinical and neuropsychological assessments,biochemical tests,Cerebrospinal Fluid(CSF),and blood sample collection in Qingdao Municipal Hospital,Shandong Province,China.Participants were divided into coffee drinking group and non-coffee drinking group,and further divided into three groups according to the frequency of coffee drinking per week: noncoffee drinking group(0 times a week),occasional coffee drinking group(less than 7times a week),and regular coffee drinking group(7 times a week).We performed multiple linear regression analyses between coffee consumption and CSF biomarkers in AD patients.The independent variables were whether to drink coffee or the frequency of drinking coffee,and the dependent variables were the levels of AD CSF biomarker(β-amyloid 40 [Aβ40],β-amyloid 42 [Aβ42],total-tau protein [t-tau],phosphorylated tau [p-tau])and the ratios of AD CSF biomarkers(Aβ42/Aβ40,ttau/Aβ42,and p-tau/Aβ42).A multiple linear regression model was used to evaluate the effect of coffee drinking on AD CSF biomarkers.Model 1 adjusted age,gender,apolipoprotein E(APOE)ε4 carrying status,educational level,and Chinese-Modified Mini-Mental State Examination(CM-MMSE)score to evaluate the effect of coffee drinking on AD CSF biomarkers;model 2 adjusted the history of hypertension,diabetes,smoking,and drinking.Further subgroup analysis stratified by age(40-65 years old and 66-90 years old)and gender groups to explore whether there is a potential correlation in specific populations.Results: As for all participants,multivariate linear analysis adjusted for potential risk factors showed no significant differences between whether to drink coffee and the frequency of drinking coffee with the levels of AD CSF biomarkers(Aβ40,Aβ42,t-tau,ptau)and the ratios of AD CSF biomarkers(Aβ42/Aβ40,t-tau/Aβ42,and p-tau/Aβ42)(all P > 0.05).Subgroup analysis by age showed that in the middle-aged population aged 44-65 years old,compared with the non-coffee drinking group,coffee drinking participants had higher level of CSF Aβ 42(β = 1.041E-03,P < 0.001)and lower ratio of CSF ptau/Aβ 42(β =-2.106E-03,P = 0.010).We also found that the frequency of drinking coffee was associated with a high level of CSF Aβ42(β = 5.892E-04,P = 0.001)and a low level of CSF p-tau/Aβ42 ratio(β =-1.420E-03,P = 0.002)in middle-aged people.However,there were no significant differences between whether to drink coffee and the frequency of drinking coffee with the levels of AD CSF biomarkers(Aβ40,t-tau,p-tau)and the ratios of AD CSF biomarkers(Aβ42/Aβ40 and t-tau/Aβ42)(all P > 0.05).In the older adults aged66-90 years old,there were no significant differences between whether to drink coffee and the frequency of drinking coffee with AD CSF biomarkers(all P > 0.05).In the subgroup analysis by gender,males with coffee drinking group had a significantly high level of Aβ42(β = 7.291E-04,P < 0.05),but no correlation was found between whether to drink coffee and the frequency of drinking coffee with other AD CSF biomarkers(all P > 0.05).In the female population,our study did not find correlation between whether to drink coffee and the frequency of drinking coffee with AD CSF biomarkers(all P > 0.05).Conclusions and Significance: Coffee drinking,especially regular coffee drinking(7times a week),was significantly associated with higher CSF Aβ42 levels and lower CSF Ptau/Aβ42 ratio compared with non-coffee consumption in cognitively normal middle-aged individuals.This protective effect may be more pronounced in male group.This study suggests that coffee consumption may play a protective role in the pathogenesis of AD(especially amyloid pathology).The findings are expected to provide new guidance for the prevention of AD in terms of lifestyle and diet.