Risk factors of young‐onset dementia: a UK Biobank study

Abstract

AbstractBackgroundWhile age is the main risk factor for developing dementia, in young‐onset dementia (YOD) symptoms can already start before the age of 65 years. Genetic factors figure more prominent in the onset of YOD than late‐onset dementia but still only account for 5‐10% of the clinical YOD cases. It is therefore important to understand how modifiable risk factors, such as lifestyle or cardiovascular factors, and their interactions with genetic factors are associated with risk for YOD. The aim of this study was to examine a comprehensive set of factors and their association with the incidence of YOD.MethodWe used data from individuals aged under 65 years (n = 356,052) in the UK Biobank, a prospective population‐based cohort, to investigate risk factors related to YOD. Incidence of dementia was determined from hospital and death records. Potential risk factors were identified from systematic reviews on late‐onset dementia and YOD, including socio‐demographic, genetic, lifestyle, environmental, blood markers, cardiometabolic, psychiatric and other factors. These were analyzed in multivariable Cox proportional hazards regression.ResultDuring 2,891,409 person‐years of follow‐up, 485 cases of YOD were reported. Incidence rates for women increased from 1.88/100,000 person‐years in age 40‐44 to 53.38/100,000 person‐years in age 60‐64. In men incidence rates increased from 5.41/100,000 person‐years in age 45‐49, to 79.54/100,000 person‐years in age 60‐64. A total of 38 variables were analyzed. In univariable analyses, 30 factors were associated with YOD, of which 15 were significantly associated with the incidence of YOD in multivariable analyses. These variables included lower formal education, lower socioeconomic status, carrying the apolipoprotein ε4 allele, no alcohol use, alcohol intoxication, social isolation, vitamin D deficiency, high c‐reactive protein levels, lower handgrip strength (i.e., higher physical frailty), hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease and depression.ConclusionThis study found potentially modifiable risk factors for YOD. While further exploration of these risk factors is necessary to validate our findings and identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD.