Heterogeneity in Modifiable and Non‐Modifiable Risk Factors among Different Dementia Types in UK Biobank

Abstract

AbstractBackgroundDementia is heterogenous and includes many subtypes, including Alzheimer’s disease (AD), frontotemporal dementia, and vascular dementia, whose risk may be expressed at different ages in life. Therefore, the modifiable antecedent risk may weigh differently in different dementia subtypes, but this heterogeneity has yet to be understood. In 2020, the Lancet Commission reported the risk for all‐cause dementia for 12 modifiable risk factors. Here, we compare the risk among these risk factors reported in the Lancet Commission 2020 to assess the heterogeneity in the association between the non‐modifiable risk factors in dementia subtypes and age groups in 450,707 participants of the UK Biobank. We also compare the risk to non‐modifiable but causal risk factors, including AD family history and the ApoE genotype.MethodWe analyzed participant data from the UK Biobank. We divided the participants into two age groups, midlife (age of diagnosis 45‐65) and late‐life (age of diagnosis greater than 65). We built four different logistic regression models corresponding to each dementia subtype in each age group, including univariate, gender‐adjusted, ethnicity‐adjusted, and gender‐ethnicity‐adjusted models. We reported the odds ratio (OR), p‐values, and 95% confidence interval. Furthermore, we compared the ORs for different risk factors from the Lancet report with those from the UK Biobank. Lastly, we ran correlations between different dementia subtypes and unknown‐cause dementia.ResultWe identified age‐dependent risk factors in different dementia types, such as ApoE genotype, hearing loss and hypertension in all‐cause and AD, and diabetes in vascular dementia. We also illustrated risk factors that are not age‐dependent risk factors, such as AD family history, air pollution, TBI, current smoking, being underweight, excessive alcohol consumption, and physical inactivity. Additionally, TBI has the greatest difference in OR compared to the Lancet report. Lastly, unknown‐underlying dementia cases have a modifiable risk profile that is highly correlated with AD and vascular dementia in both age groups.ConclusionHere, we illustrated the heterogeneity of dementia risk factors in different subtypes of dementia. Taken together, our results highlight that different dementia subtypes share/do not share the extent of risk, which could contribute to identifying patient populations for future clinical research.