Correlation Between Cancer And Dementia Risk In The Elderly Population

Objective: Due to an increasingly aging population,cancer and dementia have developed into major public health problems worldwide,placing a heavy burden on patients and the national healthcare system.In recent years,a growing body of research had shown a negative association between cancer and dementia,whereby patients diagnosed with cancer have a reduced risk of developing dementia compared to non-cancer participants.Possible explanations for this "negative association" have been suggested,one being the existence of opposing pathophysiological mechanisms between cancer and dementia,and the other being a competing risk of death in cancer patients.The study of the association between cancer and dementia still needs to be corroborated by large,multi-information studies.The purpose of this study was to investigate the association and influencing factors between cancer and dementia risk in a larger population and to explore the hypothesis of competing mortality risks proposed by previous studies.Methods: This study focused on investigating the association between cancer status and the risk of dementia and its subtypes by using multivariate Cox regression analysis to develop different models.Model 1 was adjusted primarily for age and sex,and model 2was further adjusted for education,socioeconomic status,Apo E4,body mass index,smoking status,alcohol consumption,obesity,hypertension,diabetes,heart failure,and stroke based on model 1.Hazard ratios(HRs)with 95% confidence intervals(CIs)were calculated as a measure of relative risk by comparing the observed incidence of dementia in the study population.Cumulative incidence curves for cancer and control groups were measured using the Kaplan-Meier method,and differences between the curves were calculated using Log-rank tests.The association between competing events on the risk of cancer and dementia was tested by applying the Fine-Gray sub-distribution hazard regression model.Besides,we also performed sensitivity analyses and subgroup analyses based on the type of cancer and disease confounders in model 2 to explore the association between cancer and dementia risk in depth.In addition,we did a meta-analysis of previous studies of the cancer-dementia risk association.We assessed the risk of dementia in cancer patients using the combined relative risks(RR)and 95% CI.Heterogeneity between studies was assessed using the Cochran Q statistic(P<0.1 level of significance)and the I~2 statistic.In the presence of significant heterogeneity(I~2≥50%),a random-effects model was used to calculate combined effect estimates regardless of the P-value.P-values were two-sided and the statistical significance was set at less than 0.05.All statistical analyses were performed on R statistical software version 4.1.1.Results: We enrolled a total of 263,151 participants for observational analysis,and all participants were followed from the date of recruitment until dementia diagnosis,death,loss to follow-up,or the end of the study.The mean age of participants at recruitment was60.27 years,with 142,824 female participants(54.27%).Over a median follow-up period of 9.18 years,472 cancer patients and 3,685 non-cancer patients were diagnosed with dementia,respectively.In model 1,the risk of dementia(HR: 0.89,CI: 0.81-0.98)and its subtypes(Alzheimer’s disease [AD]: 0.85 [0.74-0.98];vascular dementia [VD]: 0.81 [0.66-0.99])was reduced.The study showed that the cumulative incidence of dementia remained statistically different between cancer and non-cancer groups after controlling for competing risks of death,suggesting that death is not sufficient to explain the presence of a negative association between cancer and dementia.The inverse association between cancer and dementia risk was more pronounced in individuals aged over 60 years old(0.87 [0.76–1.00]),males(0.79 [0.66–0.95]),those without a smoking history(0.80 [0.66–0.97]),those with a BMI between 25 and 30(0.74 [0.60–0.92]),or those with a follow-up of more than10 years(0.68 [0.53–0.89]).It suggests that confounders can contribute to the negative association.The study also found that patients with male genital cancers had significantly lower risks of dementia(0.66 [0.46-0.93])and AD(0.53 [0.29-0.97]).In addition,nonmelanoma skin cancer and prostate cancer were also associated with a reduced risk of dementia(0.79 [0.62-0.99];0.69 [0.49-0.97]).Finally,the findings of the meta-analysis(all-cause of dementia: 0.89 [0.82-0.97],AD: 0.89 [0.83-0.95],VD: 0.87 [0.77-1.00])also support a negative association between cancer and dementia.Conclusions: The results of this study were consistent with previous studies,both of which suggest that cancer was associated with a reduced risk of dementia.We not only found a negative association between cancer and dementia risk but also explained the impact of survival bias on disease association proposed by previous studies through the analysis of competing risks of death.The study also observed that the presence of some confounding factors and differences in the type of cancer may reduce the risk of dementia,and the results of the Meta-analysis were consistent with the negative association found in the cohort study.