When a person younger than 65 years old begins to show signs of dementia, the first thing we tend to point to is family history — but genetics isn't the only factor that could increase the risk of young-onset dementia, according to researchers.
A new observational study published Tuesday in the peer-reviewed journal JAMA Neurology has identified 15 risk factors associated with the development of young-onset dementia, including depression, lower socioeconomic status, vitamin D deficiency and hearing impairment.
The study, which combed through data from more than 350,000 patients in the U.K., did not establish a causal relationship for risk factors, but simply observed which were more likely to be present among people who developed early dementia.
"This breakthrough study illustrates the crucial role of international collaboration and big data in advancing our understanding of dementia," David Llewellyn, a professor at the University of Exeter in the U.K. and one of the study's authors, said in a press release.
"This is the largest and most robust study of its kind ever conducted. Excitingly, for the first time it reveals that we may be able to take action to reduce risk of this debilitating condition, through targeting a range of different factors."
Dementia is the umbrella term for several diseases, including Alzheimer's disease, in which a person's memory, cognitive processing and ability to perform daily tasks see a sharp decline.
Young-onset dementia is the term for when symptoms begin to set in before the age of 65. According to the Alzheimer Society of Canada, young-onset dementia accounts for around two to eight per cent of all dementia cases.
Because dementia is predominantly an issue that affects older people, the issue of younger people developing dementia prematurely is under-researched, experts say. And the impact of young-onset dementia can be all the more destabilizing because patients don't expect it to develop so early.
"Young-onset dementia has a very serious impact, because the people affected usually still have a job, children, and a busy life," Stevie Hendriks, a researcher at Maastricht University in the Netherlands and one of the authors of the study, said in the release.
"The cause is often assumed to be genetic, but for many people we don't actually know exactly what the cause is. This is why we also wanted to investigate other risk factors in this study."
Researchers drew from the U.K. Biobank, looking at a cohort of 356,052 participants who were first assessed between 2006 and 2010. Follow-ups to track the health of participants over a long period of time were performed by the U.K. Biobank in either 2018 or 2021, depending on where the participants lived.
A total of 485 confirmed cases of young-onset dementia were recorded during the follow-up period.
In order to investigate which potential risk factors might be associated with young-onset dementia, researchers compared the 485 to the rest of the participants, using them as a control group.
Researchers looked at 39 potential risk factors and found 15 that were associated with a higher risk of young-onset dementia.
These were lower formal education, lower socioeconomic status, certain genetic markers, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high levels of a certain protein made by the liver, lower handgrip strength, hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease and depression.
Researchers noted that the association was stronger for some risk factors, namely depression, low socioeconomic status, stroke and the presence of two copies of a genetic marker called APOE ε4.
Some risk factors were affected by gender. For instance, while men with diabetes had a higher risk for young-onset dementia, that was no association found between young-onset dementia and diabetes in women.
On the other hand, women with high levels of C-reactive protein (CRP), which is created in the liver, had a higher chance of developing young-onset dementia compared to women with lower levels. However, there was no correlation seen among men.
In terms of socioeconomic factors, researchers used the Townsend deprivation index, which scores regions on four variables and assigns them a number. These variables are the per cent of people who are unemployed, who own a car, who own a home, as well as if a household is overcrowded.
Researchers found that those who belonged to the most deprived socioeconomic group were at a higher risk of developing young-onset dementia.
In those who later developed young-onset dementia, 40 per cent belonged to the most deprived socioeconomic group at their baseline assessment. Only 20 per cent of the group who did not develop young-onset dementia belonged to this group.
Handgrip strength may seem like a strange risk factor, but researchers included it to serve as a proxy for measuring general physical frailty. It's unlikely that possessing a particularly firm handshake would take dementia off the table completely — this risk factor being associated with a lower incidence of young-onset dementia is more an observation of overall physical fitness.
Another complicated risk factor was alcohol, with researchers finding that both no alcohol consumption and alcohol abuse disorder were associated with a higher risk of young-onset dementia, while moderate use was associated with a lower risk.
Researchers theorized that moderate use might be associated with lower risk because those who cut out alcohol use altogether may be doing so in response to poor overall health.
They added that while alcohol use disorder was more strongly associated with the risk of young-onset dementia, they weren't able to pin down whether or not this was a case of alcohol use disorder actually being a risk factor or whether it could be a response to young-onset dementia, as a person with impending symptoms of dementia might be more at risk of alcohol abuse prior to being diagnosed.
"Our findings regarding heavy alcohol use are complex and should be interpreted with caution," researchers noted in the study.
Some of the 15 risk factors were ones that had already been observed as risk factors for older patients, such as education level, depression and social isolation.
In this study, people who reported that they visited friends or family once a month or less were more likely to also develop young-onset dementia compared to those who reported visiting friends or family more often.
Hearing impairment, orthostatic hypotension and CRP levels have not been associated with general dementia in those aged 65 and older, researchers said. Orthostatic hypotension is when a person grows abnormally dizzy or faint when they stand or sit up abruptly due to a sudden drop in blood pressure.
Vitamin D deficiency, which was found to be associated with a higher risk of young-onset dementia, has never been studied or reported before as a risk factor for early dementia, the researchers say.
The study isn't without limitations. It doesn't look at how these risk factors actually affect the body in terms of causality, since it is an observational study. It's possible that some of the identified risk factors could actually be early symptoms of already present young-onset dementia, although researchers have tried to control for this possibility. White people are also overrepresented in the U.K. Biobank's sample, and researchers say more data is needed on ethnic and racial minorities.
Researchers noted that the 485 patients with young-onset dementia identified in this study represent a smaller incidence rate than has previously been recorded and could reflect some missing or undiagnosed cases, meaning some may have been included in the control group.
The scale of this study provides an important first step in identifying risk factors that could be included in future dementia prevention initiatives, researchers say.
"We're witnessing a transformation in understanding of dementia risk and, potentially, how to reduce it on both an individual and societal level," Leah Mursaleen, head of clinical research at Alzheimer's Research UK, said in the release. Alzheimer's Research UK co-funded the research, along with several international research organizations and councils.
"This pioneering study shines important and much-needed light on factors that can influence the risk of young-onset dementia. This starts to fill in an important gap in our knowledge. It will be important to build on these findings in broader studies."
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