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. 2024 Feb 1;81(2):134-142.
doi: 10.1001/jamaneurol.2023.4929.

Risk Factors for Young-Onset Dementia in the UK Biobank

Stevie Hendriks  1 , Janice M Ranson  2 , Kirsten Peetoom  1 , Ilianna Lourida  2 , Xin You Tai  3   4 , Marjolein de Vugt  1 , David J Llewellyn  2   5 , Sebastian Köhler  1
Affiliations

Risk Factors for Young-Onset Dementia in the UK Biobank

Stevie Hendriks et al. JAMA Neurol. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Drs Ranson and Llewellyn reported grants from Alzheimer’s Research UK and the Alan Turing Institute/Engineering and Physical Sciences Research Council. Dr de Vugt reported grants from Alzheimer Nederland and Gieskes Strijbis Fonds during the conduct of the study. Dr Llewellyn reported funding from the Medical Research Council, National Institute for Health Research Applied Research Collaboration South West Peninsula, National Health and Medical Research Council, and National Institute on Aging. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Included Participants
Figure 2.
Figure 2.. Risk Factors Associated With Incident Young-Onset Dementia in the Fully Adjusted Model
See this image and copyright information in PMC

References

    1. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9(1):63-75.e2. doi:10.1016/j.jalz.2012.11.007 - DOI - PubMed
    1. van de Veen D, Bakker C, Peetoom K, et al. ; PRECODE study group . Provisional consensus on the nomenclature and operational definition of dementia at a young age, a Delphi study. Int J Geriatr Psychiatry. 2022;37(3). doi:10.1002/gps.5691 - DOI - PMC - PubMed
    1. Hendriks S, Peetoom K, Bakker C, et al. ; Young-Onset Dementia Epidemiology Study Group . Global prevalence of young-onset dementia: a systematic review and meta-analysis. JAMA Neurol. 2021;78(9):1080-1090. doi:10.1001/jamaneurol.2021.2161 - DOI - PMC - PubMed
    1. van Vliet D, de Vugt ME, Bakker C, Koopmans RTCM, Verhey FRJ. Impact of early onset dementia on caregivers: a review. Int J Geriatr Psychiatry. 2010;25(11):1091-1100. doi:10.1002/gps.2439 - DOI - PubMed
    1. Jarmolowicz AI, Chen HY, Panegyres PK. The patterns of inheritance in early-onset dementia: Alzheimer’s disease and frontotemporal dementia. Am J Alzheimers Dis Other Demen. 2015;30(3):299-306. doi:10.1177/1533317514545825 - DOI - PMC - PubMed

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