Multiple Modifiable Risk Factors Connected to Young-Onset Dementia

Factors such as social isolation, vitamin D deficiency, and alcohol use disorder, among others, were significantly associated with a higher risk of young-onset dementia (YOD) in a recent prospective cohort study published in JAMA Neurology. 

 “Our study identified 15 lifestyle and health-related factors that were associated with YOD incidence,” authors noted. “While further exploration of these risk factors is necessary to identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD and can be readily integrated in current dementia prevention initiatives.”

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Researchers used data from the UK Biobank on participants younger than 65 years without a dementia diagnosis at baseline between 2006 and 2010. Participants in England and Scotland had follow-up until March 21, 2021, and participants in Wales had follow-up until February 28, 2018. Data analysis took place between May 2022 and April 2023.

Researchers grouped 39 possible risk factors from systematic reviews of late-onset dementia and YOD and grouped them into the following 8 domains:

1. Sociodemographic factors (ie, education, socioeconomic status, and sex),
2. Genetic factors (ie, apolipoprotein E),
3. Lifestyle factors (ie, physical activity, alcohol use, alcohol use disorder, smoking, diet, cognitive activity, social isolation, and marriage),
4. Environmental factors (ie, nitrogen oxide, particulate matter, pesticide, and diesel exposure),
5. Blood marker factors (ie, vitamin D, C-reactive protein, estimated glomerular filtration rate function, and albumin),
6. Cardiometabolic factors (ie, stroke, hypertension, diabetes, hypoglycemia, heart disease, atrial fibrillation, and aspirin use),
7. Psychiatric factors (ie, depression, anxiety, benzodiazepine use, delirium, and sleep problems), and
8. Other factors (ie, traumatic brain injury, rheumatoid arthritis, thyroid dysfunction, hearing impairment, and handgrip strength).

Multivariable Cox proportional hazards regression was used to examine the association between risk factors and YOD incidence.

A total of 356,052 participants were included—55.3% women with a mean age at baseline of 54.6 years. During 2,891,409 person-years of follow-up, 485 incident YOD cases were reported—or 16.8 per 100 000 person-years (95% CI, 15.4-18.3). 

Researchers were able to significantly associate 15 factors with a higher YOD risk, including the following: 

1. Lower formal education,
2. Lower socioeconomic status, 
3. Carrying 2 apolipoprotein ε4 allele,
4. No alcohol use,
5. Alcohol use disorder,
6. Social isolation,
7. Vitamin D deficiency,
8. High C-reactive protein levels,
9. Lower handgrip strength,
10. Hearing impairment,
11. Orthostatic hypotension,
12. Stroke,
13. Diabetes,
14. Heart disease, and
15. Depression

“Most factors are potentially modifiable and overlap with known risk and protective factors for [late-onset dementia],” authors concluded. “With external validation of our results, more risk factors for YOD could be incorporated in the prevention strategy communicated from the Lancet Commission.”
 

Reference
Hendriks S, Ranson JM, Peetoom K, et al. Risk factors for young-onset dementia in the UK Biobank. JAMA Neurol. Published online December 26, 2023. doi:10.1001/jamaneurol.2023.4929