| Background and Objective:Dementia is a degenerative disease of the central nervous system,which reduces the patient's self-care ability and social behavior,seriously affects the patient's quality of life,increases family economic and social economic expenditure,and causes tremendous psychological pressure on family caregivers.At present,there is no effective treatment method for dementia.Dementia is the main cause of disability and dependence in the elderly.The incidence and prevalence of dementia are increasing all over the world.Increasing family pressure forces people to seek support from health,financial and legal systems.Most people with dementia live in low-and middle-income countries,and respond to the elderly.It will become a challenge for society and the economy.Alzheimer's disease(AD)and vascular dementia(VaD)are the two most common types of dementia.Studies have confirmed that there is a certain degree of vascular involvement,especially microvascular disease,but caused by vascular disease.However,there is no consensus on the pathogenesis of vascular disease and Alzheimer's disease.Epidemiological studies have found that cardiovascular risk factors,such as hypertension,diabetes,hyperlipidemia,obesity and smoking,have increased the risk of dementia to a certain extent.In addition,healthy lifestyle,healthy diet and proper physical exercise can improve the health level of human body and delay the decline of cognitive function.Controlling variable vascular risk factors and promoting cardiovascular and cerebrovascular health can help prevent Alzheimer's disease and vascular dementia.In view of the fact that there is no effective treatment to prevent the progression of dementia,it is particularly important to effectively prevent dementia and reduce the risk of dementia in the absence of method to cure or alleviate the process of disease.Since various risk factors need to continue to interact for several years,it is possible to progress to dementia,thus providing an effective opportunity to prevent and delay dementia and cognitive impairment.The first prevention strategy for reducing cognitive impairment and dementia is to idengtify the risk groups.The process of degenerative neurological degeneration in Alzheimer's disease may develop and be reflected in middle age,so it is very important to identify the risk factors of dementia as early as possible.The aim of this study is to assess the association between middle-aged adjustable risk factors and dementia,and to provide some theoretical guidance for the early prevention of dementia.Methods:We systematically searched PubMed and Cochrane library on May 24,2018 to retrieve prospective cohort studies,and the search terms were“dementia”,“Alzheimer”,“Alzheimer's”,“risk”,“risk factor”,“prospective”,“cohort”,“follow”,“longitudinal”,and“nested case-control”.In addition,we also hand-searched bibliographies from existing meta-analysis and systematic review and related references,and We limited our search to studies published in English.We have two data reviewers to collect and aggregate data independently,and extract valid statistics from relevant research.If there are differences,they will be further discussed and resolved by the reviewers,and consensus will be reached.The inconsistencies will be assisted by third-party reviewers.The summary relative risk(RR)and 95%confidence interval(CI)were calculated by the random-effect model to explore the association between midlife risk factors and dementia.The Newcastle-Ottawa Scale(NOS)was used to evaluate the quality of the studies.We evaluated the heterogeneity using Cochran's Q statistic(p<0.05)and I~2 statistic(>30%).The random-effect model(DerSimonian-Laird)was used to pool the results.Sensitivity analysis and meta-regression analysis were used to perform subgroup analysis based on subject,quality score,publication year,and mean follow-up duration to explore the source of heterogeneity by eliminating one study in turn,sensitivity analysis was performed to detect the impact of individual studies on the merger results.Publication bias was examined using Begg's and Egger's tests,with the reason of asymmetry further explored via contour-enhanced funnel plot after trim and fill method.R software were used for all data analyses,and p<0.05 was considered to be statistically significant.Results:Thirty-four prospective cohort studies were included,among which 24 were eligible for meta-analysis,10 were eligible for systematic review.A total of 159,594non-demented adults were enrolled at baseline before 65 years and 13,540 people were diagnosed with dementia after follow-up.The pooled results revealed that five factors could significantly increase the dementia risk by 41 to 78%,including obesity(RR,1.78;95%CI:1.31-2.41),diabetes mellitus(RR,1.69;95%CI:1.38-2.07),current smoking(RR,1.61;95%CI:1.32-1.95),hypercholesterolemia(RR,1.57;95%CI:1.19-2.07),and hypertension(borderline blood pressure RR,1.41;95%CI:1.23-1.62 and high SBP RR,1.72;95%CI:1.25-2.37).In the heterogeneity analysis,we found that there were two studies with higher heterogeneity(high body mass index and diabetes),which may be related to the number of samples,follow-up time,inconsistent diagnostic criteria and the influence of confounding factors.Sensitivity analysis showed that there was no significant correlation between high systolic blood pressure and hypercholesterolemia and dementia after removal the study by Alonso et al.Indicating that the results were not robust enough,and the conclusion should be treated with caution,and more studies should be included to further explore.No influences due to publication bias were revealed.In the systematic review,we found another three factors,including hyperhomocysteinemia(RR,1.67;95%CI:1.10-2.57),psychological stress(HR,2.51;95%CI:1.33-4.77)and heavy drinking(RR,4.2;95%CI:1.2-15),were associated with an increased risk of dementia.In addition,physical exercise(OR,0.48;95%CI:0.25-0.91),healthy diet(OR,0.12;95%CI:0.02-0.85),and hormone therapy(HR,0.74;95%CI:0.58-0.94)in middle age were associated with the reduction of dementia risk.Conclusions:Middle-aged people with obesity,diabetes,hypertension,or hypercholesterolemia,and current smokers in midlife are at higher risk of developing dementia in late life. |
PDF Full Text Request