Dementia, a group of symptoms affecting memory, thinking, and social abilities, is highly prevalent in older adults (late-onset dementia, LOD). However, dementia can also have an early onset with symptoms occurring before the age of 65 years (young-onset dementia, YOD). It may be possible to prevent the early onset of symptoms by understanding the role of potential risk factors involved in YOD.
A study published in JAMA Neurology reported that 15 factors, comprising socioeconomic variables, genetic status, alcohol use disorder, vitamin D deficiency, medical conditions like diabetes, stroke, heart disease, etc., and social isolation, were significantly associated with YOD.
This cohort study examined the incidence of YOD and associated risk factors by analyzing data from the UK Biobank, a large population-based cohort study. The study recruited over 5,00,000 participants (aged <65 years) without a dementia diagnosis at baseline assessment between 2006 and 2010. The participants were assessed in 22 centers across the UK and underwent a comprehensive baseline assessment, including providing biological samples, completing questionnaires, and undergoing physical examination. A total of 39 potential risk factors based on systematic reviews on factors associated with YOD or LOD were identified. These factors were then grouped into domains such as sociodemographic, genetic, lifestyle, environmental, blood markers, cardiometabolic, psychiatric, and other factors. The factors were analyzed using multivariable models, adjusting for age, sex, education, socioeconomic status, and apolipoprotein (APOE) status. The analysis was done stepwise, starting with a separate analysis for each factor, then analyzing significant factors within the same domain, and finally analyzing factors across domains. The final model included 15 factors that were significantly associated with a higher risk of YOD.
The results of the study are summarized below:
1. Of the total participants (3,56,052), 55.3% were women, and the mean age at baseline was 54.6 years.
2. During the follow-up period of 2,891,409 person-years, there were 485 incident cases of YOD yielding an incidence rate of 16.8 per 100,000 person-years, with increasing incidence rates in men compared to women (Figure 1).
3. Higher formal education, lower physical frailty (handgrip strength), and alcohol use (relative to abstinence) were associated with lower incidence of YOD (Table 1).
4. Patients with 2 APOE ε4 alleles, lower socioeconomic status, high CRP levels, orthostatic hypotension, stroke, diabetes, heart disease, depression, hearing impairment, vitamin D deficiency, alcohol use disorder, and social isolation were associated with increased incidence of YOD (Table 1).
Clinical implications
The findings of this study highlighted that most of the identified risk factors for YOD are potentially modifiable. Addressing these modifiable risk factors could effectively mitigate the risk of developing YOD, and thus, should be incorporated into dementia prevention initiatives.
(Reference: Hendriks S, Ranson JM, Peetoom K, Lourida I, Tai XY, de Vugt M, Llewellyn DJ, Köhler S. Risk factors for young-onset dementia in the UK Biobank. JAMA Neurol. 2023:e234929. Doi: 10.1001/jamaneurol.2023.4929)