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Uncovering the hidden risks of early-onset dementia

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

With around 370,000 new cases each year, this research highlights an often overlooked pathology. International collaboration and big data have played a crucial role in advancing our understanding of dementia.

Highlights:

  1. The study identifies 15 risk factors for early-onset dementia, similar to those for late-onset dementia.
  2. Lower education level, socioeconomic status, genetic variation, lifestyle factors, and health conditions significantly increase risk.
  3. The findings pave the way for targeted interventions and reduction in the incidence of early-onset dementia.

Source: University of Exeter

Researchers have identified a wide range of risk factors for early-onset dementia. The findings challenge the idea that genetics are the sole cause of disease, laying the foundation for new prevention strategies.

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

Relatively little research has been done on young-onset dementia, although there are approximately 370,000 new cases of young-onset dementia each year worldwide.

Published in JAMA Neurology, the new research led by the University of Exeter and Maastricht University followed more than 350,000 participants under the age of 65 across the UK as part of the UK Biobank study. The team assessed a wide range of risk factors ranging from genetic predispositions to lifestyle and environmental influences.

The study found that lower formal education, lower socioeconomic status, genetic variation, lifestyle factors such as alcohol use disorders and social isolation, as well as health conditions such as vitamin D deficiency, depression, stroke, hearing loss and heart disease, significantly increase the risk of early onset. dementia

Professor David Llewellyn from the University of Exeter highlighted the importance of the findings: “This groundbreaking study illustrates the crucial role of international collaboration and Big Data in advancing our understanding of dementia. There is still much to learn in our current 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 type ever conducted. Interestingly, for the first time, this reveals that we may be able to take steps to reduce the risk of this debilitating disease, by targeting a range of different factors.

Dr Stevie Hendriks, researcher at Maastricht University, said: “Early-onset dementia has a very serious impact, as those affected usually still have jobs, children and busy lives. The cause is often assumed to be genetic, but for many people we don’t 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 in old age that there are a range 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 was also evident in early-onset dementia surprised me, and it could also provide opportunities to reduce risk in this group.

Support for the study was provided 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, lead researcher at the University of Exeter, said: “Our research breaks new ground by identifying that the risk of early dementia can be reduced. We believe this could herald a new era in interventions aimed at reducing new cases of this disease.

Dr Leah Mursaleen, head of clinical research at Alzheimer’s Research UK, which co-funded the study, said: “We are seeing a transformation in understanding the risk of dementia and, potentially, how to reduce it, both at an individual and societal level.

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

“This pioneering study provides important and essential insight into the factors influencing the risk of early dementia. This begins to fill an important gap in our knowledge. It will be important to build on these results in larger studies.

About this research news on dementia and neurology

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

Original research: Closed access.
“Risk factors for early dementia in the UK Biobank: a prospective population-based study” by David Llewellyn et al. JAMA Neurology


Abstract

Risk factors for early dementia in the UK Biobank: a prospective population-based study

Importance

There is little information on modifiable risk factors for early-onset dementia (YOD).

Objective

To examine factors associated with the incidence of YOD.

Design, setting and participants

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

Exhibitions

A total of 39 potential risk factors were identified from systematic reviews of late-life 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 consumption, alcohol use disorders, smoking, diet, cognitive activity, social isolation and marriage), environmental factors (nitrogen oxide, particulate matter, pesticides and diesel), blood marker factors (vitamin D, C-reactive protein, estimates based on glomerular filtration rate 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 (head trauma, rheumatoid arthritis, thyroid dysfunction, hearing loss and grip strength).

Main results and measures

Multivariate Cox proportional hazards regression was used to investigate the association between risk factors and the incidence of YOD. The factors were tested step by step, first within domains and then between domains.

Results

Of the 356,052 included participants, 197,036 (55.3%) were female and the mean (SD) age at baseline was 54.6 (7.0) years. During a follow-up of 2,891,409 person-years, 485 incident cases of YOD (251 of 485 (51.8%) males) were observed, giving 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 higher YOD risk, namely lower formal education level, lower socioeconomic status, carrying apolipoprotein ε4 allele 2, absence alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C. protein levels, low grip strength, hearing loss, orthostatic hypotension, accident 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 integrated into future dementia prevention initiatives and open new therapeutic possibilities for YOD.

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