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Relatively little research has been done on young-onset dementia, though globally there are around 370,000 new cases of young-onset dementia each year. Credit: Neuroscience News

Uncovering the Hidden Risks of Young-Onset Dementia

Summary: A new study reveals 15 risk factors for young-onset dementia, challenging the notion that genetics are the sole cause. These factors, ranging from education and socioeconomic status to lifestyle and health issues, offer hope for prevention.

With around 370,000 new cases each year, this research sheds light on a condition often overlooked. International collaboration and big data played a crucial role in advancing our understanding of dementia.

Key Facts:

  1. The study identifies 15 risk factors for young-onset dementia, similar to those for late-onset dementia.
  2. Lower education, socioeconomic status, genetic variation, lifestyle factors, and health issues significantly elevate risk.
  3. The findings open avenues for targeted interventions and reducing the incidence of young-onset dementia.

Source: University of Exeter

Researchers have identified a wide range of risk factors for young-onset dementia. The findings challenge the notion that genetics are the sole cause of the condition, laying the groundwork for new prevention strategies.

The largescale study identified 15 risk factors, which are similar to those for late-onset dementia. For the first time, they indicate that it may be possible to reduce the risk of young-onset dementia by targeting health and lifestyle factors.

Relatively little research has been done on young-onset dementia, though globally there are around 370,000 new cases of young-onset dementia each year.

Published in JAMA Neurology, the new research by the University of Exeter and Maastricht University followed more than 350,000 participants younger than 65 across the United Kingdom from the UK Biobank study. The team evaluated a broad array of risk factors ranging from genetic predispositions to lifestyle and environmental influences.

The study revealed that lower formal education, lower socioeconomic status, genetic variation, lifestyle factors such as alcohol use disorder and social isolation, and health issues including vitamin D deficiency, depression, stroke, hearing impairment and heart disease significantly elevate risk of young-onset dementia

Professor David Llewellyn of the University of Exeter emphasized the importance of the findings: “This breakthrough study illustrates the crucial role of international collaboration and big data in advancing our understanding of dementia. There’s still much to learn in our ongoing mission to prevent, identify, and treat dementia in all its forms in a more targeted way.

“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.

Dr Stevie Hendriks, Researcher at Maastricht University, said: “Young-onset dementia has a very serious impact, because the people affected usually still have a job, children, and a busy life. 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.”

Sebastian Köhler, Professor of Neuroepidemiology at Maastricht University, said: “We already knew from research on people who develop dementia at older age that there are a series of modifiable risk factors.

“In addition to physical factors, mental health also plays an important role, including avoiding chronic stress, loneliness and depression. The fact that this is also evident in young-onset dementia came as a surprise to me, and it may offer opportunities to reduce risk in this group too.”

The study’s support was supported by Alzheimer’s Research UK, The Alan Turing Institute/Engineering and Physical Sciences Research Council, Alzheimer Nederland, Gieskes Strijbis Fonds, the Medical Research Council, the National Institute for Health and Care Research (NIHR) Applied Research Collaboration South West Peninsula (PenARC), the National Health and Medical Research Council, the National Institute on Aging, and Alzheimer Netherlands.

Dr Janice Ranson, Senior Research Fellow at the University of Exeter, said: “Our research breaks new ground in identifying that the risk of young-onset dementia can be reduced. We think this could herald a new era in interventions to reduce new cases of this condition.”

Dr Leah Mursaleen, Head of Clinical Research at Alzheimer’s Research UK, which co-funded the study, said: “We’re witnessing a transformation in understanding of dementia risk and, potentially, how to reduce it on both an individual and societal level.

“In recent years, there’s been a growing consensus that dementia is linked to 12 specific modifiable risk factors such as smoking, blood pressure and hearing loss . It’s now accepted that up to four in 10 dementia cases worldwide are linked to these factors.

“This pioneering study shines important and much-needed light on factors influencing 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.’

About this dementia and neurology research news

Author: Louise Vennells
Source: University of Exeter
Contact: Louise Vennells – University of Exeter
Image: The image is credited to Neuroscience News

Original Research: Closed access.
Risk factors for young-onset dementia in the UK Biobank: A prospective population-based study” by David Llewellyn et al. JAMA Neurology


Abstract

Risk factors for young-onset dementia in the UK Biobank: A prospective population-based study

Importance  

There is limited information on modifiable risk factors for young-onset dementia (YOD).

Objective  

To examine factors that are associated with the incidence of YOD.

Design, Setting, and Participants  

This prospective cohort study used data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until March 31, 2021, for England and Scotland, and February 28, 2018, for Wales. Participants younger than 65 years and without a dementia diagnosis at baseline assessment were included in this study. Participants who were 65 years and older and those with dementia at baseline were excluded. Data were analyzed from May 2022 to April 2023.

Exposures  

A total of 39 potential risk factors were identified from systematic reviews of late-onset dementia and YOD risk factors and grouped into domains of sociodemographic factors (education, socioeconomic status, and sex), genetic factors (apolipoprotein E), lifestyle factors (physical activity, alcohol use, alcohol use disorder, smoking, diet, cognitive activity, social isolation, and marriage), environmental factors (nitrogen oxide, particulate matter, pesticide, and diesel), blood marker factors (vitamin D, C-reactive protein, estimated glomerular filtration rate function, and albumin), cardiometabolic factors (stroke, hypertension, diabetes, hypoglycemia, heart disease, atrial fibrillation, and aspirin use), psychiatric factors (depression, anxiety, benzodiazepine use, delirium, and sleep problems), and other factors (traumatic brain injury, rheumatoid arthritis, thyroid dysfunction, hearing impairment, and handgrip strength).

Main Outcome and Measures  

Multivariable Cox proportional hazards regression was used to study the association between the risk factors and incidence of YOD. Factors were tested stepwise first within domains and then across domains.

Results  

Of 356 052 included participants, 197 036 (55.3%) were women, and the mean (SD) age at baseline was 54.6 (7.0) years. During 2 891 409 person-years of follow-up, 485 incident YOD cases (251 of 485 men [51.8%]) were observed, yielding an incidence rate of 16.8 per 100 000 person-years (95% CI, 15.4-18.3). In the final model, 15 factors were significantly associated with a higher YOD risk, namely lower formal education, lower socioeconomic status, carrying 2 apolipoprotein ε4 allele, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C-reactive protein levels, lower handgrip strength, hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease, and depression.

Conclusions and Relevance  

In this study, several factors, mostly modifiable, were associated with a higher risk of YOD. These modifiable risk factors should be incorporated in future dementia prevention initiatives and raise new therapeutic possibilities for YOD.

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