Associations Between Alcohol Consumption And Cerebrospinal Fluid Biomarkers Of Alzheimer’s Disease

Objective: As the aging society intensifies,the incidence of dementia is increasing year by year.Alzheimer’s disease(AD)is a progressive neurodegenerative disease related to cognitive decline.It is the most common form of dementia in the elderly.Its typical pathological feature is Amyloid beta(Aβ)senile plaques formed by deposition and neurofibrillary tangles caused by hyperphosphorylation of tau protein.Aβ and tau biomarkers in cerebrospinal fluid(CSF)have been proven valuable in establishing prognosis in pre-clinical AD.Alcohol consumption is one of the risk factors for AD.Studies have confirmed that excessive drinking increases the risk of AD.However,the relationship between alcohol consumption and AD pathology is unclear.We sought to examine the associations between alcohol consumption and CSF AD biomarkers in cognitive intact subjects.Methods: A total of 806 cognitively intact participants who had measurements of CSF Aβ,phosphorylated tau(p Tau),total tau(t Tau)proteins and drinking characteristics were included from the Chinese Alzheimer’s Biomarker and Lifestyle(CABLE)study.According to the frequency of drinking per week,the population is divided into 4groups: never drink,<1 time/week,1-2 times/week,and >2 times/week.In order to clarify the association between alcohol consumption and CSF AD biomarker levels,we used nonlinear and multiple linear regression models for cross-sectional studies.In addition,multiple logistic regression analyses with drinking frequency as the independent variable and CSF AD biomarkers(normal vs.abnormal)as the dependent variables were conducted.In these analyses,﹤1 times/week subgroup was used as the reference.Covariates included age,gender,education,apolipoprotein epsilon-4(APOEε4)status,hypertension(yes vs no),diabetes(yes vs no),stroke(yes vs no),hyperlipemia(yes vs no),atrial fibrillation(yes vs no),and history of drinking(years).In addition,we also studied the interaction effects of age,gender and APOE ε4 status on the relationship between drinking frequency and cerebrospinal fluid biomarkers to explore the impact of their relationship on the disease process,and conduct subgroup analysis based on the interaction results.In the above analysis,P<0.05 is considered to have a significant statistical difference.Graph Pad Prism 7.00 and R 3.6.2 software were used for statistical analysis.Results: Nonlinear trends were observed between the frequency of drinking and CSF indicators of amyloid accumulation.Multiple linear regression analysis found that there were significant differences in CSF AD biomarkers between the infrequent drinking(<1time/week)and frequent drinking group(>2 times/week).After adjusting for the covariates,the frequent drinking group had higher CSF amyloid deposition related indicators than the infrequent drinking group(CSF Aβ42/Aβ40,P = 0.0400;CSF p Tau/Aβ42,P = 0.0074;CSF t Tau /Aβ42,P = 0.0046).Even after Bonferroni correction,CSF t Tau /Aβ42 is still statistically significant.Compared with the infrequent drinking group,frequent drinking was significantly associated with higher p Tau abnormalities(OR =0.6939,95% CI = 0.1098 to 1.3020,P= 0.0221)after adjusting for covariates.There was a statistically significant difference in the interaction between frequent drinking and age(P<0.05).Among the elderly(>65 years old),compared with the reference group,the frequent drinking group was associated with higher p Tau and t Tau abnormalities.Conclusions: The present study showed significant associations between drinking frequency and CSF amyloid deposition and tau phosphorylation.in cognitively intact older adults.Our findings on drinking and AD pathology further support that high-frequency drinking is a risk factor for dementia.The management of drinking may be of great significance to the early prevention of AD.